No abstract

Papillon–Lefèvre syndrome (PLS; OMIM 245000) is an autosomal recessive condition characterized by palmoplantar hyperkeratosis and periodontitis. In 1997, the gene locus for PLS was mapped to 11q14-21, and in 1999, variants in the cathepsin C gene (CTSC) were identified as causing PLS. To date, a total of 75 different disease-causing mutations have been published for the CTSC gene. A summary of recurrent mutations identified in Hungarian patients and a review of published mutations is presented in this update. Comparison of clinical features in affected families with the same mutation strongly confirm that identical mutations of the CTSC gene can give rise to multiple different phenotypes, making genotype–phenotype correlations difficult. Variable expression of the phenotype associated with the same CTSC mutation may reflect the influence of other genetic and/or environmental factors. Most mutations are missense (53%), nonsense (23%), or frameshift (17%); however, in-frame deletions, one splicing variant, and one 5′ untranslated region (UTR) mutation have also been reported. The majority of the mutations are located in exons 5–7, which encodes the heavy chain of the cathepsin C protein, suggesting that tetramerization is important for cathepsin C enzymatic activity. All the data reviewed here have been submitted to the CTSC base, a mutation registry for PLS at http://bioinf.uta.fi/CTSCbase/.

Periodontitis is caused by pathogenic subgingival microbial biofilm development and dysbiotic interactions between host and hosted microbes. A thorough characterization of the subgingival biofilms by deep amplicon sequencing of 121 individual periodontitis pockets of nine patients and whole metagenomic analysis of the saliva microbial community of the same subjects were carried out. Two biofilm sampling methods yielded similar microbial compositions. Taxonomic mapping of all biofilms revealed three distinct microbial clusters. Two clinical diagnostic parameters, probing pocket depth (PPD) and clinical attachment level (CAL), correlated with the cluster mapping. The dysbiotic microbiomes were less diverse than the apparently healthy ones of the same subjects. The most abundant periodontal pathogens were also present in the saliva, although in different representations. The single abundant species Tannerella forsythia was found in the diseased pockets in about 16–17-fold in excess relative to the clinically healthy sulcus, making it suitable as an indicator of periodontitis biofilms. The discrete microbial communities indicate strong selection by the host immune system and allow the design of targeted antibiotic treatment selective against the main periodontal pathogen(s) in the individual patients.

Our results demonstrate that PLS and HMS are phenotypic variants of the same disease and, additionally, exclude the presence of a putative genetic modifier factor within the CTSC gene that is responsible for the development of the two phenotypes. We suggest that this putative genetic modifier factor is located outside the CTSC gene, or alternatively, that the development of the different phenotypes is the consequence of different environmental or lifestyle factors.

Papillon-Lefévre syndrome (PLS; OMIM 245000) is a rare autosomal recessive condition characterized by symmetrical palmoplantar hyperkeratosis and periodontal inflammation, causing loss of both the deciduous and permanent teeth. PLS develops due to mutations in the cathepsin C gene, CTSC. Recently we have identified a Hungarian PLS family with two affected siblings. Direct sequencing of the coding regions of the CTSC gene revealed a novel seven-base deletion leading to frameshift and early stop codon in the fourth exon of the CTSC gene (c.681delCATACAT, p.T188fsX199). The affected family members carried the mutation in homozygous form, while the clinically unaffected family members carried the mutation in heterozygous form. The unrelated controls carried only the wild type sequence. In this paper we report a novel homozygous deletion of seven bases on the CTSC gene leading to the development of PLS. Since consanguineous marriage was unknown in the investigated family, the presence of the homozygous seven-base deletion of the CTSC gene may suggest that the parents are close relatives.

Fibers were spun from a mixture of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) solution of poly(lactic acid)(PLA) containing various amounts of amoxicillin (Amox) as the active component. Composition changes during spinning, structure, solubility, and the location of the drug were considered during the evaluation of drug release and microbial activity. The results showed that the composition of the material changes during the preparation procedure. The solubility of the drug in the components and that of the components in each other is limited, which results in the formation of several phases and the precipitation of the drug. The technology used results in the partitioning of the drug; some is located inside, while the rest is among the fibers. The wetting of the fibers or disks by the water-based dissolution media is poor, the penetration of the liquid into and the diffusion of the active component out of the device takes considerable time. Drug release takes place in one, burst-like step, only Amox located among the fibers dissolve and diffuse into the surrounding medium. The slow second stage of release claimed in the literature is less probable because the size of the Amox molecule is considerably larger than the holes creating the free volume of the polymer. The prepared device has antimicrobial activity, inhibits the growth of the two bacterial strains studied. The time scale of activity is short and corresponds to that of the release experiments and the burst-like behavior of the device. The results clearly prove that physical–chemical factors play a determining role in the effect and efficiency of medical devices prepared from electrospun fibers containing an active component.

Purpose: Electrospun PLA fiber devices were investigated in the form of fiber mats and disks. Metronidazole was used as an active agent; its concentration was 12.2 and 25.7 wt% in the devices. Methods: The structure was studied by X-ray diffraction and scanning electron microscopy, drug release by dissolution measurements, while the antimicrobial efficiency was tested on five bacterial strains. Results: The XRD study showed that the polymer was partially crystalline in both devices, but a part of metronidazole precipitated and was in the form of crystals among and within the fibers. Liquid penetration and dissolution were different in the two devices, they were faster in disks and slower in fiber mats, due to the morphology of the device and the action of capillary forces. Disks released the drug much faster than fiber mats. Although the release study indicated fast drug dissolution, the concentration achieved a plateau value in 24 hrs for the disks; the inhibition effect lasted much longer, 13 days for bacteria sensitive to metronidazole. The longer inhibition period could be explained by the slower diffusion of metronidazole located inside the fibers of the device. Conclusion: The results suggest that the devices may be effective in the treatment of periodontitis.

The structure-building component cetostearyl alcohol appeared to be the most convenient, thanks to its wettability and mechanical properties, which led to controlled drug release. With the use of ideal concentrations of components (10% surfactant, 40% structure-building component, 32 % lipid base, 15% antimicrobial agent and 3% polymer), sustained drug release can be provided up to nearly 3 weeks.