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IL-6 expression by oral fibroblasts is regulated by androgen.

Interleukin 6 (IL-6) is a multi-functional cytokine which has a major role in tissue damage. It is secreted by many types of cell, including oral fibroblasts, and has been implicated in the pathogenesis of periodontal diseases, particularly those associated with sex hormones. In the present study we investigated whether the androgen dihydrotestosterone (DHT) affects the expression and regulation of IL-6 in gingival fibroblasts. Using a 'capture' ELISA assay, it was found that increasing DHT concentrations progressively reduced IL-6 production by gingival cells from normal individuals and from patients with gingival inflammation and gingival hyperplasia. In contrast, cells from periodontal ligament tissue produced only barely detectable levels of IL-6. The anti-androgen cyproterone acetate acted as an androgen analogue in the gingival fibroblasts, potently inhibiting IL-6 production, and did not reverse the DHT-mediated downregulation of the cytokine. Flutamide also failed to abrogate DHT inhibition of IL-6 production, and it had no effect on IL-6 production in the absence of DHT. Moreover, semi-quantitative RT-PCR showed that DHT acted at the level of transcription of the IL-6 gene, causing a marked reduction in the relative level of IL-6 mRNA in the gingival cells.

Androgen Antagonists↗

The ultrastructural examination of gingival fibromatosis.

Hereditary gingival fibromatosis (GF) is a special type of fibrous overgrowth classified as non-inflammatory gingival enlargement. Microscopically, the connective tissue consists of coarse collagen bundles and fibroblasts. The ultrastructural examination of fibrous gingival hyperplasia reveals that fibroblasts phagocyte the mast cell granules and mast cells stimulate collagen synthesis which results in hyperplasia. In the ultrastructural examination of phenytoin-induced hyperplasia, fibroblasts, phagocytosing mast cell granules were also found. Based on these findings, the purpose of this study is to establish whether there is a relationship between fibroblasts and mast cells in GF. The gingival tissues of 5 patients with GF were examined ultrastructurally. In the connective tissue, well-defined bundles of collagen fibres were found together with fibroblasts and capillaries. There were mast cells around these capillaries which had collapsed lumens. The proximity of the mast cells and fibroblasts may indicate that mast cells play some role on collagen synthesis of fibroblasts.

Biopsy↗

Sturge Weber syndrome with intraoral manifestations. A case report.

A 15 Year old female patient with Sturge Weber Syndrome is presented. This neurocutaneous syndrome consists of angiomatosis of the skin and mucosa as well as the leptomeninges. This case report describes the classic presentation of the syndrome, emphasizing the oral manifestations. The radiographic and CT scan show the typical "tram line" intracranial calcifications. This case report presents a typical case of Sturge Weber Syndrome. It gives the radiological and CT scan findings and the important role played by them in the diagnosis of this syndrome. Emphasis is given to the differentiation of diphenylhydantoin induced gingival hyperplasia from the angiomatous enlargement of the gingiva before any treatment is planned.

Adolescent↗

Pharmacodynamic monitoring of the conversion of cyclosporine to tacrolimus in heart and lung transplant recipients.

OBJECTIVE: Conversion from cyclosporine (CsA) to tacrolimus (TRL) remains challenging in the daily routine due to individual variations in blood concentrations (pharmacokinetics, PK), pharmacodynamics (PD) and in interactions on plasma mycophenolic acid (MPA) concentrations. Therefore, we used our PD assays of lymphocyte function to monitor the conversion of CsA to TRL in heart (HTx) and lung (LTx) transplant recipients. METHODS: Patients (six HTx, two LTx) were converted from CsA to TRL because of gingival hyperplasia. All patients were treated with 6 mg BID TRL 24 hours after the last CsA dose and received mycophenolate mofetil BID cotherapy. PK measurements of CsA, TRL, and MPA were done by EMIT. Expression of cytokine production (IL-2, TNF-alpha), lymphocyte proliferation (PCNA), and activation (CD25) was assessed by FACS. RESULTS: TRL concentrations increased from day 1 to 3, but did not alter MPA concentrations, which were comparably high to MPA concentrations in combination with CsA (day 0). Compared to CsA therapy, increased TRL concentrations did not further inhibit PCNA expression, inhibited CD25 expression less on days 1 and 2 and equally high on day 3, but inhibited expression of IL-2 and TNF-alpha significantly higher on days 2 and 3 (P < .05). CONCLUSION: This study shows that monitoring PD of lymphocyte functions after conversion from CsA to TRL in HTx and LTx recipients revealed differences of inhibition of lymphocyte functions. Monitoring PD of lymphocyte function may provide insights in drug interactions of immunosuppressive combination therapy and may help to tailor immunosuppression to avoid toxicity and to enhance efficacy.

Cyclosporine↗

Drug-induced gingival enlargements.

There are many types of gingival enlargements which vary according to the etiologic factors and pathologic processes that produce them. The most common drug-induced gingival enlargement is associated with Dilantin (phenytoin). Cyclosporin and calcium channel blockers, which are increasingly used for some cardiac diseases, immunosuppression and autoimmune disorders, also cause gingival enlargement. The term "gingival hyperplasia" is an inappropriate term because enlargement is not the result of an increase in the number of cells, but rather an increase in extracellular tissue volume. This paper presents a detailed description of various drug-induced gingival enlargements, including the clinical appearance, microscopic presentation, pathogenic mechanisms and treatment options.

Anticonvulsants↗

Juvenile hyaline fibromatosis: clinical heterogeneity in three patients.

BACKGROUND: Systemic hyalinoses are genetic generalized fibromatoses characterized by an accumulation of hyalin in the dermis. Two distinctive syndromes are recognized in the literature: infantile systemic hyalinosis (ISH) and juvenile hyaline fibromatosis (JHF). ISH and JHF are sometimes difficult to separate since they show significant overlap. OBSERVATIONS: We report on 3 children from two unrelated families suffering from JHF. The first child is severely handicapped by joint contracture, massive hyperplasia of the gingivae, diffuse skin papules and subcutaneous nodules occupying the scalp, face, perianal area, palms, soles and chest. At the same age, the second child only shows pearly skin papules on the face, groin and perianal area and gingival hyperplasia without joint stiffness or any other subjective complaint. The third patient, a brother of the second child, developed mild skin abnormalities by the end of the first year. The occurrence in siblings and consanguinity in the second family suggests autosomal recessive inheritance. Histological skin examination in the 3 cases showed hyaline deposition in the dermis and abnormal ultrastructure of fibroblasts. Biochemical findings showed mucopolysaccharide abnormalities in both families. CONCLUSION: Our patients do not only illustrate the different expressions of JHF but also show some overlap with ISH, suggesting a common cause for both disorders. Genetic studies will finally answer this question.

Child, Preschool↗

Pyogenic granuloma subsequent to apical fenestration of a primary tooth.

BACKGROUND: The authors present two case reports of patients exhibiting pyogenic granulomas in the maxillary labial mucosa, which were related to an apical fenestration of a primary incisor. CASE DESCRIPTIONS: Several researchers have reported that the gingival wound and surrounding inflammatory tissue typically heal spontaneously after extraction of a fenestrated primary tooth. However, in the cases presented here, the gingival lesion did not heal after the fenestrated teeth were extracted. CLINICAL IMPLICATIONS: After extracting fenestrated teeth, clinicians need to examine the labial area at a follow-up appointment to ensure that the gingival hyperplasia heals properly. The authors suggest performing curettage of the surrounding abnormal tissue at the time of the tooth extraction.

Child↗

Inhibition of growth of human gingival fibroblasts by chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta 1.

BACKGROUND: Transforming growth factor (TGF)-beta1 is involved in the pathogenesis of both drug-induced gingival overgrowth and hereditary gingival fibromatosis. Ribozymes enzymatically cleave target mRNAs and are expected to be utilized as the basis of novel nucleic acid-based therapies. We designed a chimeric DNA-RNA ribozyme targeting TGF-beta1 mRNA and examined its effect on growth of gingival fibroblasts in culture. METHODS: Chimeric DNA-RNA hammerhead ribozyme with sequence complementary to the loop structure of human TGF-beta1 mRNA was used. We evaluated transfer of the chimeric ribozyme by hemagglutinating virus of Japan (HVJ)-envelope into cultured human gingival fibroblasts in vitro and rat gingival tissues in vivo. We then examined effects of the chimeric ribozyme to TGF-beta1 on proliferation and DNA synthesis in human gingival fibroblasts. We also examined effects of the chimeric ribozyme to TGF-beta1 on expression of TGF-beta1, type IV collagens, and fibronectin mRNAs and expression of TGF-beta1 protein in human gingival fibroblasts. RESULTS: Chimeric ribozyme was sufficiently distributed into human fibroblasts in vitro and rat gingivae in vivo. Chimeric ribozyme to TGF-beta1 significantly inhibited expression of TGF-beta1, type IV collagen, and fibronectin mRNAs and TGF-beta1 protein in human gingival fibroblasts. Mismatch ribozyme had no effect on expression of these molecules. Chimeric ribozyme to TGF-beta1 also significantly inhibited proliferation and DNA synthesis in gingival fibroblasts. CONCLUSION: Chimeric DNA-RNA ribozyme targeting TGF-beta1 may be a useful gene therapy agent for treatment of gingival hyperplasia.

Adolescent↗

The impact of chemotherapeutic agents on treatment planning.

In this article the impact of chemotherapeutic agents on planning therapy for patients with plaque associated problems are reviewed. For special patients such as those receiving systemic medications which cause xerostomia or gingival hyperplasia, topical antimicrobials are of value for utilizing chemotherapeutic agents to teach patients a "clean mouth endpoint". Once achieved, patients can use this as a goal to obtain without the use of an agent. Two mouthrinses have been clearly shown to be effective in reducing plaque and gingivitis; one contains chlorhexidine and the other essential oils. A third agent, sanguinarine, found in both a dentifrice and mouthrinse, appears to be effective when used as combined therapy and further studies of combined usage are warranted.

Administration, Topical↗

Gingival swelling as a manifestation of aplastic anemia.

Gingivitis in the preschool child is uncommon and is usually associated with underlying systemic disease such as leukemias, neutropenias, and other immunologic defects. This report describes gingival hyperplasia in a preschool child with aplastic anemia and highlights the need to exclude systemic disease in children with periodontal disease.

Anemia, Aplastic↗

[Microstructure of subcutaneous lesions in juvenile hyaline fibromatosis].

Juvenile hyaline fibromatosis is a rare autosomal recessive interstitial disease characterized by nodes and tumours of skin and soft tissues as well as by gingival hyperplasia. The authors described a case of 28-year-old male based on histopathological diagnosis. The patient was admitted to the hospital thrice in his life with the diagnosis of arthrogryphosis. Last time he presented with extensive secondary impetigo in extremities and pachydermia, polymalformation syndrome, multiple subcutaneous tumours, gingival hypertrophy, contractures, osteolytic lesions and positive family history. In histology, tumoriform lesions showed a structureless hyaline matrix often with chondroosseous metaplasia and calcium salts. More or less numerous cells in the matrix had a fibroblastoid appearance with eosinophilic cytoplasm, oval nuclei and frequently pericytoplasmic halo. Electron microscopy revealed dilated cisterns of rough endoplasmic reticulum and a hypertrophied Golgi apparatus. Particles representing calcium salts according to their density were rare. Immunohistochemistry of tumour cells showed vimentin, alpha-1-antichymotrypsin and alpha-1-antitrypsin. The findings concurred with the literature in which, nevertheless, the immunohistochemical picture were not mentioned.

Adult↗

Oral health in children with chronic renal failure.

Seventy children with chronic renal failure (CRF) aged 4-13.6 years were recruited from the Renal Unit of the Great Ormond Street Hospital for Children. Indices were recorded for dental caries, dental plaque, gingival inflammation, gingival enlargement, and enamel defects. Salivary urea, buffering capacity, and the oral streptococcal flora were determined for 25 of the children. A significantly greater proportion of the CRF children was caries free, 40% compared with 8.5% of the controls. The mean plaque score was significantly greater in the CRF group for both the primary 12.7 (16) and permanent dentition 22.0 (18.2) compared with the controls, 5.3 (7.6) and 15.5 (13.3), respectively. Eight CRF children had gingival enlargement. Enamel defects affecting the permanent teeth were observed in 57% of the CRF children compared with 33% of the controls. The buffering capacity was significantly greater in the CRF group, pH 6.4 (0.5) compared with the controls pH 5.6 (0.8). The mean salivary urea level (mmol/l) was significantly greater in the CRF children, 11.6 (5.9) compared with 3.6 (1.4) for the controls. The isolation frequency of Streptococcus mutans was significantly greater from controls compared with the CRF children ( P=0.002). An integrated dental service needs to be developed with emphasis on tooth brushing to prevent gingival hyperplasia and periodontal disease after puberty.

Adolescent↗

Periodontal treatment of two siblings with juvenile hyaline fibromatosis.

BACKGROUND AND AIM: Juvenile hyaline fibromatosis (JHF) is an autosomal recessive disease that presents with multiple subcutaneous nodular tumours, gingival fibromatosis, flexion contractures of the joint and hyaline material accumulation in extracellular area. Recently, the causative gene for JHF, capillary morphogenesis protein 2 (CMG2) was identified. In this case report, periodontal status, treatment and follow-up together with histopathologic evaluation of gingival tissue specimens and mutation screening of two JHF cases are presented. CASE REPORTS: A 10-year-old female (case 1) and her 3-year-old brother (case 2) were first examined in our department with a complaint of gingival hyperplasia in 1991. Symptoms of the disease were detected in two of four siblings in the family. Several gingivectomy operations were carried out over 11 years with hygiene motivation and initial phase therapy. After the last gingivectomy operation in 2002, the patients were reviewed frequently. RESULTS AND CONCLUSIONS: Although there was linear marginal gingival inflammation, no remarkable enlargement was noted at last appointment. Histopathological findings showed increased amounts of subepithelial nodular connective tissue, thinned epithelial mucosa, separated inter-cellular bridges and decreased numbers of connective tissue cells in gingival tissue samples. Electron microscopic examinations supported the histopathological findings. Mutation screening of CMG2 demonstrated that the siblings were homozygous for a pathogenic missense mutation, V386F. Our clinical findings demonstrate that gingivectomy is useful and frequent periodontal visits are important for maintaining oral hygiene and decreasing growth rate of gingiva in JHF.

Child↗

Conversion from cyclosporin A to tacrolimus as a non-surgical alternative to reduce gingival enlargement: a preliminary case series.

BACKGROUND: Gingival enlargement (GE) is a frequent side effect that occurs in organ transplant recipients (OTR) after the administration of cyclosporin A (CsA). The availability of new drugs used to suppress graft rejection in OTR offers an opportunity to manage GE non-surgically. This preliminary case series aimed to analyze the effect of CsA withdrawal and its substitution by another immunosuppressant in OTR with severe GE. METHODS: Four organ transplant recipients who had received a liver or renal allograft were recruited for this study. All OTR had developed clinically severe CsA-induced GE. GE scores were assessed for each patient at baseline and at weeks 2, 4, 8, 12, 16, and 54 following conversion to tacrolimus. Scaling and root planing were initially performed and repeated monthly during the first 6 months. Careful polishing of the teeth was carried out once every 2 weeks until month 6 and then monthly until month 12. Hygiene instructions and reinforcement to optimize oral hygiene were maintained throughout the study. RESULTS: The four patients showed a rapid decrease in their gingival symptoms and in the size of the gingivae. This change was clinically evident 8 weeks after conversion to tacrolimus. One year later, all the patients experienced GE regression, although some anatomic irregularities persisted in the interdental papillae of one of the patients. No adverse effects from tacrolimus were observed during the study except in one patient who presented headaches. CONCLUSION: It seems that CsA withdrawal and its conversion to tacrolimus in organ transplant recipients who develop severe gingival enlargement, together with an extensive plaque control program, provide an effective means to control/eliminate gingival hyperplasia, with minimal risk of graft dysfunction.

Adult↗

The use of free gingival grafts in the treatment of peri-implant soft tissue complications: clinical report.

Soft tissue complications including gingival hyperplasia, peri-implantitis, inadequate vestibular depth, and insufficient attached tissue may occur adjacent to endosseous implants. In most clinical cases vestibuloplasty and grafting techniques to establish a wider zone of keratinized tissue are not needed. A clinical case is presented involving peri-implant mucosal areas exhibiting persistent inflammation and progressive recession. A free gingival palatal graft was used to correct the soft tissue defects and provide optimal peri-implant health in order to increase the long-term prognosis of the implant reconstruction.

Aged↗

Treatment of cyclosporine-induced gingival overgrowth with azithromycin-containing toothpaste.

OBJECTIVES: Gingival overgrowth is a complication of cyclosporine therapy following organ transplantation. Oral azithromycin is frequently used to treat this complication. This study examined the efficacy of local azithromycin, in the form of toothpaste, against cyclosporine-induced gingival overgrowth. MATERIALS AND METHODS: Twenty stable renal transplanted patients (10 men and 10 women) with gingival hyperplasia were randomly assigned to a test group and a control group. Azithromycincontaining toothpaste had 85 mg azithromycin per gram of toothpaste. Both toothpastes were prescribed b.i.d., each time using 1.5 cm, for 1 month. All participants received scaling, root planing, polishing, and oral hygiene instructions, at least 4 weeks prior to initiation of the study. Gingival overgrowth index, bleeding on probing, blood urea nitrogen, creatinine, and serum cyclosporine levels were measured at baseline, and then again in the second and fourth weeks after tooth brushing. Patient satisfaction with the toothpastes was evaluated by a visual analogue scale. The stability of clinical responses was followed for 3 months after cessation of the toothpastes. RESULTS: Gingival overgrowth index decreased significantly in the azithromycin-containing toothpaste group (from 1.1+/-0.56 to 0.51+/-0.47, P<.001); however, in the control group, this decrease was not significant (P=.22). Bleeding on probing also decreased significantly in patients in the azithromycin-containing toothpaste group compared with controls (P=.001). When compared with baseline levels, trough levels of cyclosporine, blood urea nitrogen, and creatinine did not change in either of the groups. Patients in the control group were more satisfied with the toothpaste than were patients in the test group (53 vs 38). CONCLUSIONS: Azithromycin-containing toothpaste is an effective, simple, and noninvasive treatment for cyclosporine-induced gingival overgrowth.

Adult↗

Dental health and dental care in severely mentally retarded children.

Dental health of 103 children with severe mental retardation living in the north of Sweden, has been surveyed and compared with that of a control group of healthy children of normal intelligence. Data has been related to medical diagnosis, medication, type of residence and previous dental care. The children with severe mental retardation had been offered dental care to the same extent as the control children. Lack of cooperation in treatment and treatment under general anaesthesia was common among the SMR-children. The SMR-children who lived in institutions had a lower prevalence of caries than either those SMR-children not living in institutions or the control group. The SMR-children had a considerably higher frequency of inflamed gingival surfaces and pathological gingival pockets than the control children. The highest frequency was found among children with Down's syndrome. Gingival hyperplasias were recorded in 21% of the SMR-children. The study showed that the children with SMR had shared the generally improved dental care resources and that regular dental care had ensured that there was no neglected need for caries treatment. Periodontal health was poor and the need for stronger and appropriate preventive measures against gingivitis and periodontitis was considerable.

Adolescent↗