Biomedical subjects

T Modéer

Publications and source records attributed to T Modéer.

At least 55 records · Page 3Linked to original sources

PubMed1995

Stereologic study of cyclosporin A-induced gingival overgrowth in renal transplant patients.

Gingival biopsies were taken from 13 renal transplant patients (mean age 26.5 yr), 11 of whom exhibited cyclosporin A (CsA)-induced gingival overgrowth. Control material was obtained from seven volunteers (mean age 28 yr). Gingival tissue components were analyzed by quantitative microscopy (stereology) on 5-microns-thick sections of interdental papillae. The volume density (Vv) of different tissue components and the surface density of epithelial ridges were calculated by conventional point and intersection counting. The study showed that the volume density of oral epithelium and the surface density of the epithelial ridges in the CsA-induced gingival overgrowth were significantly increased compared to normal gingival tissue. The connective tissue of the lesion exhibited a significant increase in volume density of cells, blood vessels and non-collagenous matrix with a corresponding decrease in the collagenous matrix. These results indicate that CsA-induced gingival overgrowth represents a tissue with an altered composition characterized by increased thickness of oral epithelium and relatively increased amount of cells, vessels, non-collagenous matrix and decreased collagenous matrix in the connective tissue.

Adolescent↗

PubMed1995

Effects and interactions of tumour necrosis factor alpha and bradykinin on interleukin-1 production in gingival fibroblasts.

Effects of and interactions between tumour necrosis factor alpha (TNF alpha) and bradykinin (BK) on production of interleukin-1 (IL-1 alpha, IL-1 beta) in human gingival fibroblasts were studied. The cytokine TNF alpha induced production of cell-associated IL-1 alpha and IL-1 beta in gingival fibroblasts, with IL-1 beta being most abundant. Addition of BK, in the presence of TNF alpha, for 1 h and 6 h, respectively, synergistically enhanced the TNF alpha induced IL-1 beta production, whereas BK alone did not induce IL-1 production. Similar to BK, two phorbol esters, phorbol 12,13 dibutyrate (PDBu) and phorbol 12-myristate-13-acetate (PMA) which are known to stimulate protein kinase C (PKC), synergistically enhanced the TNF alpha induced IL-1 beta production in the gingival fibroblasts. On the contrary, a phorbol ester which does not activate protein kinase C, 13-phorbolacetate (13-PA), did not potentiate the TNF alpha induced IL-1 beta production. Similar to BK, the phorbol esters (PMA, PDBu, 13-PA) alone did not induce IL-1 beta production in the gingival fibroblasts. The results indicate that TNF alpha induces production of cell-associated IL-1 in gingival fibroblasts, which can be upregulated by a PKC dependent pathway.

Bradykinin↗

PubMed1995

Prediction of dental caries development in 1-year-old children.

Dietary habits, oral hygiene, fluoride exposure and occurrence of mutans streptococci were studied in 1-year-old children (n = 786) as well as the socio-economic and immigrant background of their parents. The purpose was to evaluate the predictive ability of variables studied in 1-year-old children that could be used to identify children at risk for early caries development. In a multivariate logistic regression analysis, the variables significantly associated with caries at 3.5 years of age were immigrant background (p < 0.001), mother's education (p < 0.001), consumption of sugar-containing beverages (p < 0.001), mutans streptococci (p < 0.05) and candy (p < 0.05). The probability of caries development was 87% when all the variables associated with caries were present at 1 year of age. The relative risk (odds ratio) of those children to develop manifest caries at 3.5 years of age was estimated to be 32 times higher than in the children where corresponding risk factors were not present. The results indicate that prediction at 1 year of age, built on risk factors associated with dental caries, can provide an indication of possible preventive interventions.

Age Factors↗

PubMed1995

Caries development in children from 2.5 to 3.5 years of age: a longitudinal study.

The development of dental caries from the age of 2.5 to 3.5 years was studied longitudinally in 692 children living in the southern suburbs of Stockholm. The parents answered a structured questionnaire concerning the family's social and immigrant background as well as the dietary habits, oral hygiene and fluoride exposure of their children. Furthermore, the occurrence of mutans streptococci and lactobacilli was determined in samples taken from the tongue of the children, and the buffer capacity of the saliva was measured. At baseline examination, 11.3% of the children exhibited dental caries. At follow-up, 1 year later, decayed and/or filled surfaces were registered in 36.7% of the subjects. The majority of the new lesions were located on the occlusal surfaces of the second molar. Ninety-two percent of the children with caries at baseline developed new carious lesions during the 1-year period, compared to 29% of the children who were caries-free at baseline (p < 0.001). Of the lesions diagnosed at baseline as initial caries, 64% progressed to manifest lesions during the 1-year period. The study indicates that children with early caries development exhibit high caries progression as well as a high risk for further development of an extensive number of new carious lesions.

Chi-Square Distribution↗

PubMed1993

The phenytoin metabolite p-HPPH upregulates prostaglandin biosynthesis in human gingival fibroblasts challenged to interleukin-1.

The effects of and interactions between the major phenytoin (PHT) metabolite 5-parahydroxyphenyl-5-phenylhydantoin (p-HPPH) and interleukin-1 (IL-1 alpha, IL-1 beta) or tumor necrosis factor alpha (TNF alpha) on prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1 alpha, IL-1 beta and TNF alpha, dose-dependently, stimulated PGE2 formation in gingival fibroblasts. The metabolite, p-HPPH (1.2-2.4 micrograms/ml), did not induce PGE2 formation itself but potentiated IL-1 alpha and IL1 beta induced PGE2 formation in the gingival fibroblasts in a manner dependent on the concentration of both IL-1 and p-HPPH. The metabolite also stimulated IL-1 induced formation of 6-Keto PGF1 alpha, the stable breakdown product of PGI2, in a dose dependent manner. IL-1 beta induces release of [3H]-arachidonic acid ([3H]-AA) from prelabelled fibroblasts, which was potentiated by p-HPPH (> or = 1.2 micrograms/ml). TNF alpha (> or = 1 ng/ml) significantly stimulated the biosynthesis of PGE2 by a process that was also potentiated by p-HPPH. Addition of exogenous, unlabelled AA (10 microM) caused an increase of PGE2 formation in the fibroblasts that was not potentiated by p-HPPH (1.6 micrograms/ml). The results indicate that treatment with p-HPPH results in upregulation of prostaglandin synthesis in gingival fibroblasts challenged to IL-1 or TNF alpha at the level of phospholipase A2.

Cells, Cultured↗

PubMed1993

Epidermal growth factor potentiates interleukin 1 and tumor necrosis factor-induced prostaglandin biosynthesis in human gingival fibroblasts.

The effects of and interactions between epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF-alpha) on arachidonic acid release and prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1 alpha, IL-1 beta and TNF-alpha, but not EGF nor TGF-alpha, stimulated prostaglandin E2 (PGE2) formation in the gingival fibroblasts. The effect of IL-1 alpha, IL-1 beta and TNF-alpha on PGE2 formation was significantly potentiated by EGF in a dose-dependent manner. Similarly, TGF-alpha synergistically potentiated IL-1 beta stimulated PGE2 formation. IL-1 beta but not EGF stimulated the release of 3H-arachidonic acid (3H-AA) from prelabelled gingival fibroblasts. In contrast to the effect on PGE2 formation, no synergistic interaction between EGF and IL-1 was seen on arachidonic acid (AA) release. Addition of unlabelled exogenous AA, in the presence of EGF, resulted in a significant increase in PGE2 formation compared to that seen in fibroblasts not exposed to EGF. The results demonstrate that EGF and IL-1 as well as EGF and TNF-alpha act in concert to enhance prostanoid formation in gingival fibroblasts. Data indicates that EGF potentiates the IL-1 and TNF-alpha induced PGE2 formation at the level of prostaglandin endoperoxide synthase (cyclooxygenase). The synergistic effects of inflammatory cytokines and growth factors may be of physiological importance for regulation of regenerative tissue growth during inflammation and repair.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Cyclosporin-A-induced gingival overgrowth in renal transplant children.

Gingival overgrowth was assessed in renal transplant children, 19 boys and 13 girls, aged 2.5-18 yr, who had been on a cyclosporin-A (CsA)-based immunosuppressive regimen for at least 12 months. Data collected included number of posttransplant months, total CsA dose administered during the first 6 posttransplant months, oral dose and blood trough level of CsA on the day of examination, plaque accumulation (VPI%), gingival inflammation (GBI%), loss of attachment, and gingival overgrowth. Thirteen percent of the children exhibited gingival overgrowth characterized by one or more units with increased sulcus probing depth (> or = 4 mm), i.e. pseudopockets. The total amount of CsA administered during the first 6 posttransplant months was significantly higher in the children with gingival overgrowth than in those without. The study indicates that the development of CsA-induced gingival overgrowth is positively related to the total dose of the drug administered to the children during the first 6 posttransplant months.

Administration, Oral↗

PubMed1993

Caries prevalence in 2.5-year-old children.

The prevalence of caries and gingivitis was determined clinically in 2.5-year-old children (n = 832) living in the southern suburbs of Stockholm. The occurrence of mutants streptococci and lactobacilli was determined in samples taken from the tongue and the buffer capacity of the saliva was measured. The parents answered a structured questionnaire concerning their children's dietary habits, oral hygiene, fluoride exposure and their social and ethnic background. Initial or manifest caries was diagnosed in 11.7 and 6.4% of the subjects, respectively. Seventy-two percent of the total number of caries lesions were localized to the maxillary incisors. Caries prevalence in children with an immigrant background was significantly higher (p < 0.001) than in children without. In the multivariate analysis, the variables significantly associated with caries were: colonization with mutans streptococci (p < 0.001), lactobacilli (p < 0.01) and children with immigrant background (p < 0.01). The study demonstrates an association between early colonization of cariogenic microflora and an increased risk of developing dental caries in very young children.

Chi-Square Distribution↗

PubMed1992

Bradykinin induces a B2 receptor-mediated calcium signal linked to prostanoid formation in human gingival fibroblasts in vitro.

The aim of the study was to determine the effect of bradykinin (BK) on the level of cytoplasmic-free Ca2+, [Ca2+]i, in human gingival fibroblasts and its relation to BK-induced prostanoid formation. BK, but not des-Arg9-BK, induced a significant rapid (within seconds) and transient increase in [Ca2+]i, that was not dependent on extracellular Ca2+. The stimulatory effect of BK was seen in concentrations at or above 10(-8) M, with the most pronounced effect at 10(-6) M. D-Arg0-Hyp3-Thi5,8-DPhe7-BK, a BK B2 receptor antagonist, but not des-Arg9-Leu8-BK, a BK B1 receptor antagonist, blocked BK-induced rise in [Ca2+]i. The BK B2 receptor antagonist also significantly reduced BK-induced PGE2 formation. When extracellular Ca2+ in the incubation medium was depleted, either by addition of EGTA or by omission of Ca2+ addition, BK still caused a significant stimulation of PGE2 formation. The calcium ionophores A23187 and ionomycin, similar to BK, caused a burst of PGE2 formation. The two phorbol esters phorbol 12,13-dibutyrate and 4-beta-phorbol-didecanoate positively amplified calcium ionophore A23187-induced PGE2 formation. The results indicate that BK-induced PGE2 formation in gingival fibroblasts is coupled to an increase in [Ca2+]i mediated by the BK B2 receptor, and which is independent of extracellular Ca2+.

Bradykinin↗

PubMed1992

Actinobacillus actinomycetemcomitans, Capnocytophaga and Porphyromonas gingivalis in subgingival plaque of adolescents with Down's syndrome.

Levels of Actinobacillus actinomycetemcomitans, Capnocytophaga and Porphyromonas gingivalis were determined in subgingival plaque samples from 37 adolescents with Down's syndrome and 37 healthy controls matched with respect to age and sex. Gingival inflammation, supra- and subgingival calculus, periodontal pockets ( > 4 mm) and alveolar bone loss were registered. Alveolar bone loss was more frequent in Down's syndrome subjects (32%) than in the controls (3%). A. actinomycetemcomitans was detected in the subgingival plaque in 35% of the Down's syndrome adolescents and in 5% of the controls. On site level, A. actinomycetemcomitans and Capnocytophaga were more frequent in the subgingival plaque samples of Down's syndrome children than in those of controls. Comparing Down's syndrome subjects positive or negative for A. actinomycetemcomitans and Capnocytophaga, no significant differences were found in terms of gingival inflammation, periodontal pockets ( > 4 mm) or number of sites with alveolar bone loss. The results indicate an altered microbial composition of the subgingival plaque of Down's syndrome subjects compared with healthy controls, with higher frequency of A. actinomycetemcomitans.

Adolescent↗

PubMed1992

Phenytoin potentiates interleukin-1-induced prostaglandin biosynthesis in human gingival fibroblasts.

1. The effect of phenytoin (PHT) on prostaglandin E2 (PGE2) biosynthesis in human gingival fibroblasts stimulated by interleukin-1 (IL-1 alpha, IL-1 beta) or by tumour necrosis factor alpha (TNF alpha) was studied. 2. IL-1 alpha (1.5-6.0 ng ml-1) and IL-1 beta (30-300 pg ml-1), dose-dependently, stimulated PGE2 formation, in 24 h cultures, with IL-beta being the most potent agonist. 3. PHT (2.5-20 micrograms ml-1) did not induce PGE2 formation itself but potentiated IL-1 alpha- and IL-1 beta-induced PGE2 formation in the gingival fibroblasts in a manner dependent on the concentrations of both IL-1 and PHT. 4. IL-1 beta (0.1-1.0 ng ml-1) induced release of [3H]-arachidonic acid ([3H]-AA) from prelabelled fibroblasts that was potentiated by PHT (20 micrograms ml-1). 5. TNF-alpha (greater than or equal to 0.01 micrograms ml-1) significantly stimulated the biosynthesis of PGE2 by a process that was potentiated by PHT. 6. Addition of exogenous arachidonic acid (AA) (greater than or equal to 1 microM) caused an increase of PGE2 formation in the fibroblasts that was not potentiated by PHT (20 micrograms ml-1). 7. The results indicate that treatment with PHT results in upregulation of prostaglandin biosynthesis in gingival fibroblasts challenged with IL-1 or TNF alpha, at least partly due to enhanced level of phospholipase A2 activity.

Arachidonic Acid↗

PubMed1992

Enhanced prostaglandin biosynthesis in human gingival fibroblasts isolated from patients treated with phenytoin.

Prostaglandin E2 (PGE2) formation was studied in human gingival fibroblasts derived from three epileptic patients before and after 9 months of phenytoin (PHT) therapy. Interleukin 1 (IL-1 alpha; 0.3-6.0 ng/ml), (IL-1 beta; 10-1000 pg/ml) and tumour necrosis factor (TNF alpha; 0.01-0.1 microgram/ml) dose-dependently stimulated the formation of PGE2 in 24 h cultures. In fibroblasts, derived after 9 months of PHT therapy, IL-1 alpha, IL-1 beta and TNF alpha induced a significantly higher formation of PGE2 compared to that in fibroblasts derived before PHT therapy. IL-1 beta induced a significantly higher release also of 3H-arachidonic acid (3H-AA) from prelabelled PHT fibroblasts compared to that in prelabelled gingival fibroblasts isolated before the drug therapy. Addition of exogenous AA caused a spontaneous increase of PGE2 formation in PHT fibroblasts compared to that in fibroblasts isolated before the PHT treatment. The results indicate that PHT medication results in an upregulation of prostanoid formation in gingival fibroblasts partly due to an increased phospholipase A2 activity and partly due to an increased cyclooxygenase activity.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Levels of cyclosporin-A (CsA) in saliva in children after oral administration of the drug in mixture or in capsule form.

The cyclosporin-A (CsA) level in human unstimulated whole saliva was studied in 5 children, aged 9-16 yr, receiving the immunosuppressive drug CsA following renal allograft transplantation. The time-concentration relationship of CsA in saliva was determined in the children who were taking the drug orally in mixture form (n = 3) as well as in capsule form (n = 3). For the mixture, the median maximal level of CsA in whole saliva was 2867 ng/ml compared to 5.4 ng/ml for the capsule. The oral mucosal exposure of CsA during the dosage interval was approximately 130 times higher when the drug was administered in mixture form than in capsule form. The study demonstrates that gingival tissue is exposed to a considerable concentration of CsA throughout the dosage interval in patients taking CsA in mixture form. Therefore the vehicle in which the drug is administered should be considered in the pathogenesis of CsA-induced gingival overgrowth.

Administration, Oral↗

PubMed1991

Bradykinin B1 and B2 receptor agonists synergistically potentiate interleukin-1-induced prostaglandin biosynthesis in human gingival fibroblasts.

The interactions between bradykinin (BK) and interleukin-1 (IL-1) on prostaglandin formation in human gingival fibroblasts have been studied. IL-1 alpha and IL-1 beta stimulated prostaglandin E2 (PGE2) formation in the gingival fibroblasts with IL-1 beta being the most potent agonist. The effects of both IL-1 alpha and IL-1 beta on PGE2 biosynthesis was synergistically potentiated by BK, in a dose-related manner. The synergistic interaction between IL-1 beta and BK on PGE2 production was seen both with B1 (des-Arg9-BK) and B2 (BK, Lys-BK) BK receptor agonists. No synergistic interaction between BK and IL-1 beta was seen on arachidonic acid release. These data suggest that BK and IL-1 act in concert to enhance prostanoid formation in inflammatory lesions and that the level of interaction is distal to phospholipase activity.

Arachidonic Acid↗

PubMed1991

Immunohistological study of neuronal markers in inflamed gingiva obtained from children with Down's syndrome.

The histological appearance of the gingiva in children with Down's syndrome (DS) was studied with special reference to inflammatory involvement and innervation. A dense infiltration of inflammatory cells was seen in the propria of most of the DS patients, including a few polymorphonuclear leucocytes. A hyperplasia of the epithelium was also found. The innervation of the gingiva was studied using immunohistochemistry. Nerve fibers as well as nerve bundles immunoreactive to neurofilament (NF) were seen in the propria, while occasionally intraepithelial NF fibers were observed. Calcitonin gene-related peptide (CGRP)-immunoreactive fibers and fiber bundles were also visualized, but they were less abundant than NF fibers. The density of NF and CGRP fibers and fiber bundles was estimated by semiquantitative evaluation. A higher density of NF and CGRP immunoreactive structures was observed in the propria of DS patients compared to the control subjects, while no obvious alteration was seen in their distribution in the propria. In addition, sparsely distributed fibers immunoreactive to peptide histidine isoleucine amide (PHI) and vasoactive intestinal polypeptide (VIP) fibers as well as neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were seen, mainly surrounding blood vessels. A few substance P (SP) fibers were also found, mostly close to the epithelium. No obvious differences of these sparsely distributed fibers were seen in the DS patients compared to controls. Thus, a profound inflammatory involvement of the gingiva of DS patients is seen concomitant with a hyperinnervation of the presumed sensory component of the gingival innervation. In contrast, no alterations were seen in the density of neuronal markers related to autonomic nerve fibers. The sensory hyperinnervation observed is probably not specifically related to DS, but may be due to a sprouting of afferent nerves induced by the inflammatory reaction. However, factors released from the sensory afferents could contribute to the gingival inflammation seen in DS.

Adolescent↗

PubMed1991

Craniofacial growth in bone marrow transplant recipients treated with growth hormone after total body irradiation.

The effect of growth hormone (GH) treatment on craniofacial development was studied in five children exhibiting growth retardation following bone marrow transplantation. Linear and angular measurements were made on lateral radiographic cephalograms taken prior to the start of GH treatment and after an average treatment time of 1.2 yr. The results showed that the mean growth increments of mandibular length in the GH treated children, exceeded the corresponding values of the control group by 150% during the period of investigation. It is suggested that this dimensional increase in the patients was due to GH stimulation on the chondral growth process in the mandibular condyles.

Adolescent↗

PubMed1991

Influence of phenytoin on cytoplasmic free Ca2+ level in human gingival fibroblasts.

Influence of 5,5-diphenylhydantoin (phenytoin; PHT) on the cytoplasmic free Ca2+ concentration, [Ca2+]i, was studied in fura 2 loaded adherent monolayers of human gingival fibroblasts derived from three patients before and after 9 months of PHT therapy. In the patient where gingival overgrowth developed during PHT medication (responder), addition of PHT to gingival fibroblasts derived before PHT medication induced a transient extracellular Ca2+ dependent increase in [Ca2+]i. In a non-responder patient, where gingival overgrowth did not develop during the same period of PHT therapy, addition of PHT to gingival fibroblasts derived before the start of medication did not significantly affect [Ca2+]i. Under extracellular Ca2+ deficient conditions, addition of PHT to serum-starved fibroblasts derived from the two categories of patients before the medication resulted in an increase in [Ca2+]i. In fibroblasts derived from the responder patient during PHT medication, in contrast to those from the non-responders (n = 2), the basal level of [Ca2+]i was significantly decreased. The results indicate that, in the cases studied, there is a relationship between PHT induced alterations in [Ca2+]i in gingival fibroblasts and the clinical development of gingival overgrowth.

Calcium↗

PubMed1991

Retrospective study of children with hypophosphatasia with reference to dental changes.

In the present retrospective study different dental and medical parameters have been analyzed in 17 Swedish children with established hypophosphatasia (HP). It was demonstrated that the basis for the establishment of the diagnosis varied among different dentists and physicians, and that the diagnostic parameters studied among the children varied. The most reliable parameters for HP included raised levels of phosphoethanolamine in urine, and clinical and radiologic findings associated with the legs. These findings were found among the children more often than lowered values of alkaline phosphatase in serum. Histologic analysis of an extracted tooth made a valuable diagnostic complement. It is concluded that a better diagnostic uniformity is recommended. In a well functioning collaboration with well defined tasks, both dentists and physicians can contribute to a reliable diagnosis.

Adolescent↗