Biomedical subjects

T Modéer

Publications and source records attributed to T Modéer.

At least 37 records · Page 2Linked to original sources

PubMed1999

Signal transduction pathways involved in the synergistic stimulation of prostaglandin production by interleukin-1beta and tumor necrosis factor alpha in human gingival fibroblasts.

Accumulating evidence indicates that prostaglandins play an important role in the pathogenesis of periodontal disease. In this study, the effects and interactions between IL-1beta and TNFalpha on prostaglandin production and its regulation were investigated. The cytokines IL-1beta and TNFalpha stimulated prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in gingival fibroblasts. Simultaneous treatment of the cells with IL-1beta and TNFalpha resulted in a synergistic stimulation of PGE2 and PGI2 formation. IL-1beta and, to a lesser extent, TNFalpha stimulated the release of 3H-arachidonic acid (3H-AA), and simultaneous addition of IL-1beta and TNFalpha further increased the release of 3H-AA from pre-labeled gingival fibroblasts. Furthermore, IL-1beta and, to a lesser extent, TNFalpha induced the expression of cyclooxygenase-2 (COX-2) mRNA. Simultaneous addition of IL-1beta and TNFalpha synergistically enhanced COX-2 mRNA levels, accompanied by a corresponding stimulation of PGE2 synthesis. Neither IL-1beta, TNFalpha, nor the combination of these two cytokines affected COX-1 mRNA levels. PMA, known to activate protein kinase C (PKC), enhanced the stimulatory effect of IL-1beta, TNFalpha, and the combination on COX-2 mRNA levels accompanied by a corresponding increase in PGE2 production. The phospholipase A2 (PLA2) inhibitor, BPB, and the PKC inhibitor, BIS, reduced PGE2 production, whereas dexamethasone, indomethacin, and NS-398 completely abolished PGE2 production induced by IL-1beta, TNFalpha, and the combination. The study indicates that the synergistic stimulation of prostaglandin production by IL-1beta, and TNFalpha is mediated partly at the level of COX-2 and partly at the level of PLA2 and that PKC is involved in the signal transduction of the synergy between the two cytokines. The synergy between IL-1beta and TNFalpha may play an important role in the inflammatory processes in gingival tissue in vivo.

Arachidonic Acid↗

PubMed1998

Bradykinin synergistically stimulates interleukin 6 production in human gingival fibroblasts challenged with interleukin 1 or tumour necrosis factor alpha.

The production of interleukin 6 (IL-6) was studied in human gingival fibroblasts challenged with bradykinin (BK), in the presence or absence of either tumour necrosis factor alpha (TNF-alpha) or interleukin 1 (IL-1). The inflammatory mediator BK as well as the cytokines TNF-alpha and IL-beta dose dependently stimulated IL-6 production in gingival fibroblasts. When the cells were treated simultaneously with BK and either IL-1 beta or TNF-alpha, the inflammatory mediator BK synergistically upregulated IL-6 production in a dose-dependent manner. The BK B1 receptor agonist des-arg9-BK as well as the BK B2 receptor agonist Lys-BK also induced IL-6 production and synergistically enhanced the effect of IL-1 and TNF-alpha on the production of IL-6. The upregulation of IL-6 production induced by BK was abolished by the anti-inflammatory agent dexamethasone (DEX) and the phospholipase A2 (PLA2) inhibitor 4-bromphenacyl bromide (BPB). Treatment of the cells with the cyclooxygenase (COX) inhibitor flurbiprofen resulted in a minor reduction of the stimulatory effect of BK. The results show that BK together with IL-1 or TNF-alpha act in concert to enhance IL-6 production and that the synergy was obtained by both the BK B1 and the BK B2 receptor agonist. The study indicates that the synergy between BK and IL-1 or TNF-alpha on IL-6 production is mediated partly at the level of PLA2 and partly at the level of COX. The synergism between the pro-inflammatory mediator BK and the cytokines IL-1 or TNF-alpha indicates that gingival fibroblasts, by producing cytokines, affect the local immune response in the connective tissue and thereby play a role in the pathogenesis of periodontal disease.

Acetophenones↗

PubMed1998

Effect of a chlorhexidine/thymol-containing varnish on prostaglandin E2 levels in gingival crevicular fluid.

The aim was to study the effect of a chlorhexidine/thymol-containing varnish (Cervitec) on the levels of prostaglandin E2 (PGE2) in gingival crevicular fluid (GCF). The material consisted of 25 adolescents and young adults with fixed orthodontic appliances exhibiting gingival inflammation. Four buccal sites, adjacent to bands and brackets, were selected on each patient and randomly treated with either a varnish containing chlorhexidine diacetate (1% w/w) and thymol (1% w/w) or a placebo varnish without active ingredients. After baseline registration, the varnishes were applied twice within 3 d. Follow-up examinations were performed after 3, 8 and 30 d. The gingival inflammation was assessed by bleeding on probing, volume of GCF with a Periotron 8000 and PGE2 level in GCF by using a radioimmuno assay. Compared with baseline, a statistically significant reduction in the volume of GCF was recorded at the chlorhexidine/thymol treated sites in contrast to the placebo. The mean PGE2 levels were significantly reduced after the test varnish treatment compared with baseline and differed significantly from placebo after 8 d. The findings suggest that treatments with the antibacterial varnish result in reduced gingival inflammation and may thus be beneficial for patients with fixed orthodontic appliances.

Adolescent↗

PubMed1998

Effect of triclosan on interleukin-1 beta production in human gingival fibroblasts challenged with tumor necrosis factor alpha.

The effect of the dentifrice ingredient triclosan (2,4,4'-trichloro-2'-hydroxyldiphenyl ether) on the production of interleukin (IL)-1beta and IL-6 was studied in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNFalpha) in vitro. When gingival fibroblasts were treated simultaneously with triclosan (0.25, 0.5 microg/ml) and TNFalpha (10 ng/ml), the stimulatory effect of TNFalpha on IL-1beta production was reduced by the agent. In situ hybridisation showed that the TNFalpha-induced expression of IL-1beta mRNA was significantly reduced by triclosan. Furthermore, when the cells were treated simultaneously with a known protein kinase C (PKC) activator, phorbol 12-myristate-13-acetate (PMA) and TNFalpha in the presence of triclosan (0.5 microg/ml), the agent reduced the production of IL-1beta. In contrast to its effect on IL-1beta, triclosan did not influence the mRNA expression or the production of IL-6 induced by TNFalpha. The finding that triclosan reduces the production of the inflammatory mediator IL-1beta in gingival fibroblasts further supports the view that triclosan exhibits an anti-inflammatory effect.

Anti-Infective Agents, Local↗

PubMed1998

Gingival crevicular fluid from patients with periodontitis contains bone resorbing activity.

Inflammatory processes occurring in the vicinity of bone tissue often result in stimulation of osteoclast activity and loss of skeletal mass. The aim of the current study was to determine if inflammatory exudates collected from gingival pockets in patients with periodontitis contain factors capable of stimulating resorptive activity. The degree of bone mineral mobilization and bone matrix degradation was assessed by analysis of the release of 45Ca and 3H from bones prelabelled with 45CaCl2 and [3H]proline, respectively. Gingival crevicular washings from six patients with signs of periodontitis stimulated 45Ca or 3H release from the calvarial bones. The stimulatory effect of the gingival crevicular washings on 45Ca release was concentration- and time-dependent, and reduced by calcitonin, a specific osteoclast inhibitor. These data demonstrate that crevicular fluid contains factor(s) which can stimulate osteoclastic degradation of bone in vitro. The bone resorbing activity was partially retained after extensive dialysis. Analysis of the concentrations of prostaglandin E2, interleukin-1alpha and interleukin-1beta in the crevicular fluids, and comparisons of these agents as stimulators of 45Ca release in the mouse calvarial assay, suggest that prostaglandin E2 is not the sole factor responsible for the bone resorbing activity of the exudates. The data indicate that other factors, such as IL-1, may play key roles in the stimulation of osteoclastic activity by gingival crevicular washings.

Adolescent↗

PubMed1998

Periodontal conditions and salivary immunoglobulins in individuals with Down syndrome.

Periodontal conditions and salivary levels of immunoglobulins sIgA, IgM, and IgG subclass distribution and albumin, quantified by enzyme-linked immunosorbent assay, were determined in 20 patients with Down syndrome and 19 healthy controls. Gingival inflammation was more extensive (P < 0.05) among Down syndrome subjects compared to controls as well as the occurrence of periodontal pockets (> 4 mm) (P < 0.05). The immunoglobulin levels of sIgA, IgM, the sum of IgG subclasses, and the concentration of albumin did not differ significantly between the 2 groups. However, the proportion of IgG1 expressed as percentage of the sum of total IgG was significantly higher (P < 0.01) in the Down syndrome group compared to controls. On the contrary, the proportion of IgG2, IgG3, and IgG4 subclasses in saliva did not differ between the 2 groups. The results indicate an altered distribution of IgG subclasses in saliva, with a higher proportion of IgG1 in Down syndrome individuals compared to controls.

Adolescent↗

PubMed1997

Renal function in cyclosporine-treated pediatric renal transplant recipients in relation to gingival overgrowth.

BACKGROUND: Transplant immunosuppression using cyclosporine (CsA) leads to renal dysfunction as well as gingival overgrowth. The underlying alteration in both these lesions is characterized by an excessive accumulation of extracellular matrix components (fibrosis). To investigate the relationship between CsA-induced nephrotoxicity and gingival overgrowth, the renal function as well as the occurrence of gingival overgrowth was evaluated in pediatric renal transplant recipients: 38 boys and 30 girls, ranging in age from 2 to 20 years, who had been on a CsA-based immunosuppressive regimen for at least 12 months. METHODS: Gingival overgrowth was determined on the basis of measurements of sulcus depth and was diagnosed as positive when the probing depth was > or = 4 mm without exhibiting a loss of periodontal attachment. Renal function tests were performed using inulin and para-aminohippuric acid clearances for evaluating glomerular filtration rate, effective renal plasma flow (ERPF), and filtration fraction (FF). RESULTS: Nineteen percent of the children exhibited gingival overgrowth. The occurrence of gingival overgrowth was positively related (P<0.05) to the mean oral daily dose of CsA, the mean CsA trough blood level, and concomitant administration of nifedipine. The children who were on antihypertensive treatment exhibited lower ERPF and significantly higher FF than the normotensive children. The mean FF value was significantly higher (P<0.05) in the children with gingival overgrowth than in those without gingival overgrowth, whereas glomerular filtration rate and ERPF did not differ between the two groups. CONCLUSIONS: The study suggests that there is a positive correlation between the degree of gingival enlargement and changes in renal function expressed as filtration fraction.

Adolescent↗

PubMed1997

Cyclosporin A upregulates prostaglandin E2 production in human gingival fibroblasts challenged with tumor necrosis factor alpha in vitro.

The effect of cyclosporin A (CsA) on prostaglandin E2 (PGE2) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-alpha) was studied. TNF-alpha (1-100 ng/ml) dose-dependently stimulated PGE2 formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE2 formation itself but potentiated TNF-alpha induced PGE2 formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-alpha. TNF-alpha (10 ng/ml) stimulated the release of [3H]-arachidonic acid (AA) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 microM/ml) to the cells resulted in enhanced PGE2 formation that was not potentiated by CsA (100 ng/ml). Furthermore, CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-alpha (10 ng/ml), although PGE2 formation was enhanced. The results indicate that CsA and TNF-alpha act in concert on PGE2 formation in gingival fibroblasts, which may be of importance in the pathogenesis of gingival overgrowth induced by the drug.

Adult↗

PubMed1997

Dental maturity in children of short stature, with or without growth hormone deficiency.

The aim of this investigation was to study dental maturity in healthy prepubertal children of short stature (height<-2 SD), with or without growth hormone (GH) deficiency, compared to healthy controls. The GH-deficient group (GH level<10.0 microg/l) included 29 children (11 female, 18 male) with a mean age of 10.2+/-2.2 years. The GH non-deficient group consisted of 17 children (5 female, 12 male) with a mean age of 8.5+/-2.1 years. All the children were evaluated for serum concentrations of IGF-1, alkaline phosphatase (ALP), triiodthyronin (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and fasting plasma insulin; height and bone age were also recorded. Dental maturity was determined from panoramic radiographs. The mean difference between the dental and chronological ages was -0.67+/-0.89 years in the GH-deficient group compared to 0.23+/-1.07 years in their controls: in the GH non-deficient group the difference was -0.95+/-0.82 years compared to controls 0.16+/-1.06 years in their controls. Compared to chronological age, both bone and dental age were lower in the GH-deficient and GH non-deficient groups. It is concluded that children of short stature, both GH-deficient and GH non-deficient. exhibit a delayed dental age compared to their chronological age- and sex-matched controls. A multiple stepwise regression analysis showed that the sitting height and GH level were the only significant factors associated with dental maturity.

Age Determination by Skeleton↗

PubMed1997

Prostaglandin E2 level in gingival crevicular fluid from patients with Down syndrome.

The levels of prostaglandin E2 (PGE2) and interleukin-1 beta (IL-1 beta) were determined in gingival crevicular fluid (GCF) collected from patients with gingivitis: 15 Down syndrome children and 15 controls. The mean level of PGE2 in GCF was significantly higher (P < 0.05) in the Down syndrome group (10.0 pg/microliters GCF) than in the control group (4.6 pg/microliters GCF). In GCF samples collected from sites characterized as noninflamed, the mean level of PGE2 was significantly higher (P < 0.001) in the Down syndrome group than in the controls. The mean level of PGE2 in samples from inflamed sites, on the other hand, did not differ between the two groups. The mean level of IL-1 beta was not significantly higher in the Down syndrome group than in the controls. This study shows that the level of PGE2 detected in GCF from Down syndrome patients is increased, a fact that may be of importance in the pathogenesis of the periodontal disease frequently seen in these patients.

Adolescent↗

PubMed1996

Oral carriage of Candida species in children and adolescents with Down's syndrome.

Oral carriage of Candida albicans was studied in 55 children and adolescents with Down's syndrome (DS), aged between 7 months and 20 years 6 months, and compared with an age- and sex-matched control group of subjects. Twenty-two of the DS subjects were diagnosed as having congenital cardiovascular malformations. Compared to controls, the DS subjects were more prone to infections. The number of subjects colonized with C. albicans in the oral cavity was significantly higher in the DS group (69%) than in the control group (35%). Colonization with C. albicans and simultaneous erythematous or white pseudomembranous lesions of the oral mucosa were diagnosed in 22 (40%) of the DS groups and in only one of the control group. In both the DS and the healthy control subjects the frequency of colonization with C. albicans was positively correlated to age. The DS subjects were significantly more densely colonized by C. albicans than the controls. Abnormalities of the immune response in DS children may contribute to the increased oral carriage of C. albicans.

Adolescent↗

PubMed1996

Triclosan reduces prostaglandin biosynthesis in human gingival fibroblasts challenged with interleukin-1 in vitro.

The effect of the toothpaste ingredient triclosan (2,4,4'-trichloro-2'-hydroxyldiphenyl ether) on the prostaglandins biosynthesis in human gingival fibroblasts challenged with interleukin-1beta (IL-1beta) or tumor necrosis factor alpha (TNFalpha) was studied in vitro. When gingival fibroblasts were treated simultaneously with triclosan and IL-1beta, the stimulatory effect of IL-1beta on prostaglandin E2 (PGE2) and PGI2 formation was reduced in a dose-dependent manner by triclosan. Triclosan also reduced the PGE2 formation induced by TNFalpha. Furthermore, the capacity of IL-1beta to induce release of [3H] arachidonic acid from prelabelled gingival fibroblasts was reduced in the presence of triclosan. Addition of exogenous unlabelled arachidonic acid (AA) to the cells resulted in enhanced PGE2 formation which was reduced by triclosan. The upregulation of the metabolism of AA to PGE2 induced by IL-1beta, was markedly reduced in the presence of triclosan. The study indicates that the stimulatory effect of IL-1beta on prostanoid formation (PGE2, PGI2) in human gingival fibroblasts was diminished in the presence of triclosan partly at the level of phospholipase A2 and partly at the level of cyclooxygenase. The present data that triclosan, in vitro, inhibits the production of inflammatory mediators such as prostaglandins suggests that this can be an aspect of its clinical effect on gingivitis, in addition to its antibacterial effect.

Adult↗

PubMed1996

Effect of phenytoin on interleukin-1 beta production in human gingival fibroblasts challenged to tumor necrosis factor alpha in vitro.

Effects and interaction of tumor necrosis factor alpha (TNF alpha) and the antiepileptic drug phenytoin (PHT) on interleukin-1 beta (IL-1 beta) production as well as on prostaglandin E2 (PGE2) formation were studied in gingival fibroblasts in vitro. TNF alpha, in contrast to PHT, dose-dependently stimulated the production of cell-associated IL-1 beta. The stimulatory effect of TNF alpha on IL-1 beta production was accompanied by enhanced PGE2 formation. When PHT and TNF alpha were added simultaneously, the drug potentiated the stimulatory effect of TNF alpha on both IL-1 beta production and PGE2 formation. The major PHT metabolite, p-HPPH, did not affect IL-1 beta production, either alone or in combination with TNF alpha. The production of IL-1 beta induced by TNF alpha and the combination of TNF alpha and PHT was further enhanced in the presence of the prostaglandin endoperoxide (PGH) synthase inhibitors, indomethacin and flurbiprofen. The PHT-mediated enhancement of TNF alpha-induced IL-1 beta production and PGE2 formation in gingival fibroblasts may be an important link in the pathogenesis of gingival overgrowth induced by PHT.

Child↗

PubMed1996

Interleukin-1 beta and phenytoin reduce alpha 1 (I) procollagen mRNA expression in human gingival fibroblasts.

Effects of and interactions between interleukin-1 beta (IL-1 beta) and phenytoin (PHT) on alpha 1 (I) procollagen gene and protein expression in human gingival fibroblasts and its relation to prostaglandin E2 (PGE2) formation were studied. IL-1 beta (300 pg/ ml) reduced the steady-state level of alpha 1 (I) procollagen mRNA by 50% and decreased the amount of procollagen I by 35%. PHT (10 micrograms/ml) reduced the level of alpha 1 (I) procollagen mRNA by 40% but the amount of procollagen I in the medium was unchanged. In combination with IL-1 beta, PHT potentiated the inhibitory effect of IL-1 beta on alpha 1 (I) procollagen mRNA level that was accompanied by an increased PGE2 formation. Preincubation with indomethacin (10(-6) M) partially reduced the inhibitory effect of IL-1 beta as well as of IL-1 beta in combination with PHT on the mRNA level of alpha 1 (I) procollagen. The inhibitory effect of PHT was unaffected by indomethacin treatment. Addition of exogenous PGE2 (> or = 10 nM) dose-dependently reduced steady-state level of alpha 1 (I) procollagen mRNA as well as the amount of procollagen 1. The study indicates that IL-1 reduces the expression of alpha 1 (I) procollagen mRNA in human gingival fibroblasts partly by a prostaglandin endoperoxide (PGH) synthase-mediated pathway and partly by a PGH-synthase independent pathway, whereas PHT reduces alpha 1 (I) procollagen gene expression by a PGH-synthase independent pathway. The potentiation of the inhibitory effect of IL-1 induced by PHT was mediated mainly by a PGH-synthase dependent pathway.

Anticonvulsants↗

PubMed1996

Stepwise prediction of dental caries in children up to 3.5 years of age.

The present study is a part of a prospective, longitudinal investigation of caries development in children (n = 692) living in the southern suburbs of Stockholm. The aim was to evaluate, longitudinally, the caries-predictive ability of variables describing social and immigrant background, dietary habits, microbial and oral hygiene factors, and fluoride exposure in children at 1 and 2.5 years of age with respect to caries development before the age of 3.5. The predictors for caries development in children before 2.5 years of age were mutans streptococci (p < 0.01), immigrant background (p < 0.01), and consumption of candy (p < 0.01). The predictors for developing manifest caries between 2.5 and 3.5 years of age were mutans streptococci (p < 0.001), mother's education (p < 0.001), immigrant background (p < 0.01), and consumption of candy (p < 0.05) and sugar-containing beverages (p < 0.05). The caries incidence at 2.5 years of age as well as the caries increment between 2.5 and 3.5 years of age were significantly higher in children with immigrant background compared to non-immigrants. This study indicates that the possibility of identifying children at risk for caries development increases longitudinally from 1 to 3.5 years of age and there was a synergistic effect between age and each predictor.

Age Factors↗

PubMed1996

Effect of palatal plate therapy in children with Down syndrome. A 1-year study.

The effect of palatal plate therapy on oral dysfunction in children with Down syndrome was studied during a 1-year period. Twenty-nine subjects with a mean age of 24 months were randomized to a test group or to a control group. The variables concerning orofacial muscle function--that is, "closed mouth', "tip of the tongue visible', "open mouth', "inactive protrusion of the tongue', and "active protrusion of the tongue'--were monitored by video recordings. After 12 months of therapy the mean duration of the factor "closed mouth' was significantly longer (p < 0.001) and "inactive protrusion of the tongue' significantly shorter (p < 0.001) in the test group than in the control group. The results indicate that in children with Down syndrome, palatal plate therapy may be a valuable complement to a training program for improving orofacial muscle function.

Child, Preschool↗

PubMed1996

Gingival overgrowth in renal transplant patients administered cyclosporin A in mixture or in capsule form. A longitudinal study.

Cyclosporin A (CsA)-induced gingival overgrowth was longitudinally studied in 45 adult renal transplant patients randomly assigned to be administered CsA orally in mixture or in capsule form. After 1 year of CsA therapy, 37% of the mixture and 43% of the capsule patients exhibited gingival overgrowth. In mixture patients gingival overgrowth was present, already after 1 month of CsA therapy and, after 12 months, mixture patients exhibited an increased number of sites with gingival overgrowth in the regions of the upper front and lower molars compared to capsule patients. In addition, the relative increase in gingival width of the interdental papillae of the maxillary central incisors and the mandibular first molars, measured buccolingually on stone casts, was also higher in mixture patients than in capsule patients. In a stepwise multiple logistic regression analysis, the use of nifedipine and the total CsA dose administered during the first 6 posttransplant months were the predictors associated with gingival overgrowth. The study suggests that concomitant administration of nifedipine in renal transplant patients should be avoided and a change from the mixture form of CsA to the capsule form should be considered in order to minimize the development of CsA-induced gingival overgrowth.

Adult↗

PubMed1995

Interleukin-1 beta induces expression of cyclooxygenase-2 mRNA in human gingival fibroblasts.

The effect of interleukin-1 beta (IL-1 beta) on the expression of cyclooxygenase-1 and -2 (COX-1 and COX-2) mRNA and its relation to prostaglandin E2 (PGE2) biosynthesis in human gingival fibroblasts was studied. IL-1 beta increased levels of mRNA for COX-2 whereas the COX-1 mRNA level was unaffected. The increased COX-2 mRNA levels were accompanied by enhanced PGE2 formation. The phorbol, 12-myristate 13-acetate (PMA), known to stimulate protein kinase C (PKC), also induced expression of COX-2 mRNA. When gingival fibroblasts were treated simultaneously with IL-1 beta and PMA, the cytokine IL-1 beta synergistically increased levels of COX-2 mRNA, accompanied by a corresponding increase in PGE2 biosynthesis. The anti-inflammatory steroid, dexamethasone (DEX) abolished the enhanced expression of COX-2 mRNA as well as PGE2 formation induced by IL-1 beta, PMA or the combination of IL-1 beta and PMA. The study indicates that the IL-1 beta induced PGE2 formation is mediated by an enhanced gene expression of COX-2 in gingival fibroblasts suggesting that the enzyme COX-2 may play an important role in the regulation of prostanoid formation at inflammatory lesions in gingival tissue.

Base Sequence↗