Gingival crevicular fluid vascular endothelial cell growth factor and platelet-derived growth factor-BB release profile following the use of perforated barrier membranes during treatment of intrabony defects: a randomized clinical trial.

BACKGROUND AND OBJECTIVE: Perforated barrier membranes open channels between the suprabony and intrabony compartments of the defect, which could allow for more physiologic cellular interactions between different components of the periodontium during guided tissue regeneration surgery. To test this assumption, this study was designed to evaluate levels of vascular endothelial cell growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in gingival crevicular fluid during the early stages of healing of localized intrabony defects treated with perforated membranes (PMs) or non-PMs, as compared with open flap debridement. MATERIAL AND METHODS: Thirty non-smoking patients with severe chronic periodontitis participated in this prospective, randomized and single blinded trial. Each patient contributed one interproximal defect that was randomly assigned to the PM group (n = 10), occlusive membrane (OM) group (n = 10) or open flap debridement (OFD) group (n = 10). Plaque index, gingival index, probing depth, clinical attachment level and the intrabony depth of the defect were measured at baseline and reassessed at 6 and 9 mo after therapy. Gingival crevicular fluid samples were collected on days 1, 3, 7, 14, 21 and 30 d after therapy for the changes in VEGF and PDGF-BB levels. RESULTS: During the early stages of healing (1, 3 and 7 d), the mean VEGF and PDGF-BB concentrations at sites treated with PMs and OFD peaked with a statistically significant difference as compared with the OM-treated group. VEGF and PDGF-BB levels at sites treated with PMs and OFD were not statistically different. Growth factor levels decreased sharply in the samples obtained at days 21 and 30 with non-significant differences between the three groups. Nine months after therapy, the PM-treated group showed a statistically significant improvement in probing depth, clinical attachment level and intrabony defect compared to the OM and OFD groups. CONCLUSIONS: Within the limits of the present study, one can conclude that PM coverage of periodontal defects is associated with initial gingival crevicular fluid growth factor upregulation that could improve the clinical outcomes of guided tissue regeneration surgery.

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

Sublocalization of the Papillon-Lefevre syndrome locus on 11q14-q21.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive form of palmoplantar ectodermal dysplasia, characterized by palmoplantar hyperkeratosis and severe early-onset periodontitis. The presence of severe periodontitis distinguishes PLS from other palmoplantar keratodermas. As part of our efforts to study the genetic basis of periodontitis susceptibility, we performed a genome-wide search to identify major loci for PLS in 44 individuals (14 affected) from 10 consanguineous PLS families. We have identified evidence for linkage of a PLS gene on 11q14-q21. A maximum two-point logarithm of the odds (LOD) score of 8.24 was obtained for D11S1367 at a recombination fraction of theta=0.00. Multipoint analysis resulted in a LOD score of 10.45 and placed the gene for PLS within a 4-5 cM genetic interval. This genetic interval, flanked by D11S4197 and D11S931, contains more than 50 cDNAs and 200 expressed sequence tags (ESTs). This refinement of the candidate region for a PLS gene is in agreement with other recent reports of linkage for PLS to chromosome 11q14-q21 and should help in identification of the gene for PLS.

A short-term study of the effects of SBHAN, a novel compound, on gingival inflammation in the beagle dog.

Unique hydroxyl ion-modulating compounds based on the amino acid glycine have been developed that possess both antimicrobial and pro-healing properties. The purpose of the present study was to determine the effects of one of these compounds, 8.5% (w/v) sodium N, N-bis-2 (hydroxylethyl) aminoacetate (SBHA) with 0.3% (w/v) NaOH (SBHAN) on ligature-induced gingival inflammation in the beagle dog. Fifteen purebred beagle dogs were subjected to a 14-day oral hygiene regimen, consisting of manual scaling and daily toothbrushing with plain pumice. Gingival inflammation was then initiated by tying ligatures around 12 study teeth per dog and by placing the dogs on water-softened dog chow. After 30 days, ligatures were removed, dogs were placed on a hard diet and randomly assigned to five treatment groups by the flip of two coins. The five treatments included: 1) distilled, pyrogen-free water; 2) 8.5% (w/v) SBHAN; 3) 4.3% (w/v) SBHAN; 4) 0.12% chlorhexidine; and 5) 8.5% SBHA (w/v) (SBHAN without added NaOH). Solutions were placed in opaque spray bottles to shield their identity from the examiner. Treatment consisted of a daily aerosol application of 2 ml of each solution in a calibrated spray bottle to the affected teeth. The following measures were taken from the dogs at baseline (after hygienic phase), 30 days after initiation of gingival inflammation (before ligature removal), and 2 weeks and 4 weeks after ligature removal: 1) plaque index (PI); 2) gingival index (GI); 3) probing depths (PD); 4) relative attachment levels (RAL); and 5) gingival crevicular fluid volume (GCF). Analysis of subgingival plaque for anaerobic and aerobic colony forming units/ml was also performed at each time point. Gingival biopsies were performed, sectioned and stained with hematoxylin and eosin to quantify the inflammatory cell infiltrate (ICI). After ligature placement, increases were observed in PI, GI, PD, RAL, GCF, aerobic and anaerobic subgingival microbial counts, and ICI. After ligature removal, spontaneous resolution of gingival inflammation and plaque accumulation around the teeth of all dogs was observed with any treatment. Statistical analysis (Tukey's pairwise comparisons) of the mean PI, GI, PD, RAL, ICI, and GCF after 4 weeks of treatment with each agent, however, revealed that 8.5% SBHAN was significantly (P < 0.05) more effective than water, 4.3% SBHAN, or 8.5% SBHA in reducing PI, GI, PD, and GCF, but not RAL or ICI. Moreover, 0.12% chlorhexidine was more effective than water, 4.3% SBHAN, or 8.5% SBHA at reducing GI, PD, and GCF, but not PI, RAL, or ICI. No adverse reactions to the SBHAN were observed visually or histologically in any of the dogs during the course of the investigation. These data suggest that further investigation in a larger study population of the potential of SBHAN as an anti-gingivitis compound is warranted.

Coinheritance of two rare genodermatoses (Papillon-Lefèvre syndrome and oculocutaneous albinism type 1) in two families: a genetic study.

The co-occurrence of two rare recessive genetic conditions in apparently unrelated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultaneously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syndrome and type 1 oculocutaneous albinism. The families were tested for mutations in the causative genes, cathepsin C (CTSC) and tyrosinase (TYR), respectively, by direct sequencing. To assess the relationship of the two families, both families were tested for polymorphisms at eight microsatellite markers spanning both CTSC and TYR loci. Independent mutations (c.318-1G-->A and c.817G-->C/p.W272C) were identified in CTSC and TYR, respectively, that were shared by the affected individuals in both families. The two affected genes lie close together on chromosome bands 11q14.2-14.3, and studies with linked genetic markers suggested that the families shared a small chromosomal segment carrying both mutations that had been transmitted intact from a remote common ancestor. The co-occurrence of the two rare diseases in multiple families depends on their shared chromosomal location, but not on any shared pathogenic mechanism.