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Background: Assessment of the effect of subgingival instrumentation (SI) on systemic inflammation in periodontitis grades B (BP) and C (CP). Methods: In this prospective cohort study, eight BP and 46 CP patients received SI. Data were collected prior to and 12 weeks after SI. Blood was sampled prior to, one day, 6, and 12 weeks after SI. Neutrophil elastase (NE), C-reactive protein (CRP), leukocyte count, lipopolysaccharide binding protein, interleukin 6 (IL-6) and IL-8 were assessed. Results: Both groups showed significant clinical improvement. NE was lower in BP than CP at baseline and 1 day after SI, while CRP was lower in BP than CP at baseline (p < 0.05). NE and CRP had a peak 1 day after SI (p < 0.05). Between-subjects effects due to CP (p = 0.042) and PISA (p = 0.005) occurred. Within-subjects NE change was confirmed and modulated by grade (p = 0.017), smoking (p = 0.029), number of teeth (p = 0.033), and PISA (p = 0.002). For CRP between-subjects effects due to BMI (p = 0.008) were seen. Within-subjects PISA modulated the change of CRP over time (p = 0.017). Conclusions: In untreated CP, NE and CRP were higher than in BP. SI results in better PPD and PISA reduction in BP than CP. Trial registration: Deutsches Register Klinischer Studien DRKS00026952 28 October 2021 registered retrospectively.

To evaluate the stability of attachment achieved in infrabony defects by regenerative treatment over 60 ± 12 months compared to control teeth.Patients treated regeneratively in at least one infrabony defect between 2004 and 2010 were screened for this retrospective cohort study. Complete examinations available for baseline, 12 and 60 ± 12 months after surgery, and a respective control tooth without treatment, provided eligibility for analysis.Twenty-seven patients (age 58 ± 11.7 years; 12 females, five smokers) were included, each contributing one infrabony defect and one control tooth. Regenerative therapy resulted in significant attachment gain (2.7 ± 1.6 mm; p 0.001) after 1 and (3.0 ± 2.2 mm; p 0.001) 5 years. Control teeth were stable (vertical probing attachment level [PAL-V] change: 1 year: 0 ± 0.8 mm; 5 years: -0.2 ± 1.2 mm). The study did not detect any significant change of PAL-V from 1 to 5 years after surgery for regenerative (-0.3 ± 2.4 mm) and control teeth (-0.2 ± 1.4 mm). Multivariate analysis associated smoking and generalized recurrence of periodontitis (amount of sites with PPD 5 mm) with attachment loss.PAL-V achieved by regenerative therapy in infrabony defects is as stable over 5 years as periodontally reduced but gingivally healthy or gingivitis sites. Smoking and periodontitis recurrence are associated with attachment loss.

BACKGROUND AND OBJECTIVE Long-term tooth retention is the ultimate goal of periodontal therapy. Aim of this study was to evaluate tooth loss (TL) during 10 years of supportive periodontal therapy (SPT) in periodontal compromised patients and to identify factors influencing TL on patient level. MATERIAL AND METHODS Patients were re-examined 120 ± 12 months after active periodontal therapy. TL and risk factors [smoking, initial diagnosis, SPT adherence, interleukin-1 polymorphism, cardiovascular diseases, age at baseline, bleeding on probing (BOP), change of practitioner, insurance status, number of SPT, marital and educational status] influencing TL on patient level were assessed. RESULTS One-hundred patients (52 female, mean age 65.6 ± 11 years) lost 121 of 2428 teeth (1.21 teeth/patient; 0.12 teeth/patient/y) during 10 years of SPT. Forty-two of these were lost for periodontal reasons (0.42 teeth/patient; 0.04 teeth/patient/y). Significantly more teeth were lost due to other reasons (P

Aim Assessment of the effect of nonsurgical periodontal therapy on haematological parameters in patients with grades B (BP) and C periodontitis (CP). Methods Eight BP and 46 CP patients received full-mouth periodontal debridement within 48 h, if positive for Aggregatibacter actinomycetemcomitans with adjunctive systemic antibiotics (4 BP, 17 CP). Clinical data were collected prior and 12 weeks after periodontal therapy. Blood was sampled prior to and 1 day as well as 6 and 12 weeks after the first SD visit. Erythrocyte count, haemoglobin value, haematocrit (HCT), mean erythrocyte volume (MCV), mean corpuscular haemoglobin (MCH), MCH concentration (MCHC), platelets (PLT) and heat shock protein 27 (Hsp27) were assessed. Results Both groups showed significant clinical improvement (p p ≤ 0.005) and Hsp27 increased noticeably at 1 day (p Conclusion Based on multivariate analysis, periodontal diagnosis (BP/CP) was not associated with haematological parameters measured in this study or serum Hsp27. In CP, nonsurgical periodontal therapy improved MCHC 12 weeks after SD. Also in CP Hsp27 was increased 1 day after SD.

This study aims to evaluate long-term stability of attachment achieved in infrabony defects (IBDs) by regenerative treatment.All patients who had received regenerative treatment for at least one IBD between 2004 and 2010 were screened for this retrospective case series. If complete examinations (plaque/gingival index, probing depth [PD], vertical clinical attachment level [CAL-V]) were available for patients at baseline and 12 months after surgery, they were invited for reexamination 60 ± 12 months after surgery. Reexamination involved testing for interleukin (IL)-1 polymorphism and counting number of supportive periodontal treatment (SPT) visits. Forty-one patients (24 males and 17 females; age, median: 62.0 years, lower/upper quartile: 49.8/68.3 years; six smokers, and 9 IL-1 positive) were included for analysis, each contributing one IBD.Regenerative therapy resulted in significant attachment gain after 1 (median: -3 mm, lower/upper quartile: -1.5/-4 mm; P0.001) and 5 (median: -3 mm, lower/upper quartile: -1.9/4.5 mm; P0.001) years. The study failed to detect median change of CAL-V from 1 to 5 years after surgery (median: 0 mm; lower/upper quartile: -1/1.5 mm; P = 0.84). Multiple regression analysis identified that number of SPT visits is correlated with CAL-V gain from 1 to 5 years after surgery. IL-1 polymorphism and percentage of sites with PD6 mm at 5-year reexamination are correlated with CAL-V loss from 1 to 5 years after surgery.CAL-V achieved by regenerative therapy in IBDs may have retained stability over 5 years. Frequent SPT is associated with stability. IL-1 polymorphism and generalized reinfection are associated with less stability.

This study aims to analyze factors influencing treatment results in aggressive (AgP) and chronic (ChP) periodontitis. ChP [probing pocket depth (PPD) ≥ 3.5 mm, attachment loss ≥ 5 mm at >30 % of sites; age > 35 years] and AgP (clinically healthy; PPD ≥ 3.5 mm at >30 % of sites, radiographic bone loss ≥ 50 % at 2 teeth; age ≤ 35 years) were examined prior and 3 months after nonsurgical therapy according to the full-mouth disinfection concept. Adjunctive systemic antibiotics were used if Aggregatibacter actinomycetemcomitans had been detected at baseline. In 31 ChP (12 female, 10 smokers; 4,808 sites) and 28 AgP (16 female, 9 smokers; 4,769 sites), overall mean PPD reductions were less favorable in AgP (0.9 ± 0.5 mm) than in ChP (1.3 ± 0.4 mm; p = 0.033). PPD reductions and relative vertical probing attachment level gain were more favorable at sites with initial PPD ≥ 6 mm, bleeding on probing, and for adjunctive systemic antibiotics. Furthermore, PPD reductions were more favorable for increased baseline tooth mobility and maxillary teeth, whereas AgP, female sex, and multirooted teeth were associated with less favorable PPD reduction. Regarding PPD reduction, AgP responded less favorably to nonsurgical treatment than ChP.

Papillon-Lefevre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low-cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss-of-function mutation in CTSC, indicating that they suffer from a PLS-like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.

Papillon-Lefèvre syndrome (PLS) is characterised by aggressively progressive periodontitis combined with palmo-plantar hyperkeratosis. It is caused by "loss of function" mutations in the cathepsin C gene. The hypothesis behind this study is that PLS patients' polymorphonuclear leukocytes (PMNs) produce more proinflammatory cytokines to compensate for their reduced capacity to neutralize leukotoxin and to eliminate Aggregatibacter actinomycetemcomitans. Production of more interleukin (IL)-8 would result in the attraction of more PMNs. The aim of this study was to evaluate the cytokine profile in PLS patients' blood cultures. Blood was sampled from eight PLS patients (one female) from six families (antiinfective therapy completed: six; edentulous: two) with confirmed cathepsin C mutations and deficient enzyme activity. Nine healthy males served as controls. Whole blood cultures were stimulated with highly pure lipopolysaccharide (LPS) from Escherichia coli R515 and IL-1β plus tumor necrosis factor (TNF)-α. Thereafter, release of IL-1β (stimulation: LPS and LPS plus adenosine triphosphate), IL-6, IL-8, interferon-inducible protein (IP)-10, and interferon (IFN)-γ (stimulation: LPS, IL-1β/TNFα) were detected by ELISA. Medians of cytokine release were, with the exception of IP-10, slightly higher for PLS than for controls' cultures. None of these differences reached statistical significance. Increased production of IL-1β, IL-6, IL-8, IP-10, or IFNγ as a significant means to compensate for diminished activity and stability of polymorphonuclear leukocyte-derived proteases could not be confirmed in this study. Cytokine profiles in blood cultures may not be used to identify PLS patients.

Objective: To compare the subgingival microbiota of aggressive and chronic periodontitis (ChP) using single-site and pooled plaque samples. Methods: In 60 patients with aggressive or ChP, subgingival plaque was sampled from the four deepest pockets using two sterile paper points simultaneously. One paper point from each pocket was put in a separate transport vial, the second was pooled with the three other paper points of a respective patient. The content of each vial was analysed for Aggregatibacter actinomycetemcomitans, Tannerella forsythensis, Porphyromonas gingivalis, and Treponema denticola. Results: Pooled plaque samples detected higher numbers for all tested pathogens than single-site samples. Detection frequencies were similar for both strategies. Using single-site samples, A. actinomycetemcomitans detection rate was statistically significantly a higher in aggressive than in ChP (p=0.01). A. actinomycetemcomitans was found in higher numbers, the other pathogens in lower numbers in aggressive than in ChP. Neither presence nor absence of one of the tested bacteria had sufficient positive or negative predictive value for aggressive periodontitis. Conclusion: A. actinomycetemcomitans was detected in higher numbers and frequency in aggressive than in ChP. Its detection may confirm the clinical diagnosis and influence therapy. As a diagnostic test, its sensitivity and predictive value was low.

Generation of the soluble interleukin-6 receptor (sIL-6R) is a prerequisite for pathogenic IL-6 trans-signaling, which constitutes a distinct signaling pathway of the pleiotropic cytokine interleukin-6 (IL-6). Although in vitro experiments using ectopically overexpressed IL-6R and candidate proteases revealed major roles for the metalloproteinases ADAM10 and ADAM17 in IL-6R shedding, the identity of the protease(s) cleaving IL-6R in more physiological settings, or even in vivo, remains unknown. By taking advantage of specific pharmacological inhibitors and primary cells from ADAM-deficient mice we established that endogenous IL-6R of both human and murine origin is shed by ADAM17 in an induced manner, whereas constitutive release of endogenous IL-6R is largely mediated by ADAM10. Although circulating IL-6R levels are altered in various diseases, the origin of blood-borne IL-6R is still poorly understood. It has been shown previously that ADAM17 hypomorphic mice exhibit unaltered levels of serum sIL-6R. Here, by quantification of serum sIL-6R in protease-deficient mice as well as human patients we also excluded ADAM10, ADAM8, neutrophil elastase, cathepsin G, and proteinase 3 from contributing to circulating sIL-6R. Furthermore, we ruled out alternative splicing of the IL-6R mRNA as a potential source of circulating sIL-6R in the mouse. Instead, we found full-length IL-6R on circulating microvesicles, establishing microvesicle release as a novel mechanism for sIL-6R generation.

Background Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor. Aim We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood. Methods To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients. Results Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37. Conclusions Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease. Electronic supplementary material The online version of this article (doi:10.1186/s13023-014-0148-y) contains supplementary material, which is available to authorized users.

Whereas neutrophil elastase, cathepsin G, and proteinase 3 have been known as granule-associated serine proteases of neutrophils for decades, a fourth member, called neutrophil serine protease 4 (NSP4), was just recently described and provisionally characterized. In this study, we identified NSP4 as a novel azurophil granule protein of neutrophils by Western blot analyses of subcellular fractions as well as by RT-PCR analyses of neutrophil precursors from human bone marrow. The highest mRNA levels were observed in myeloblasts and promyelocytes, similar to myeloperoxidase, a marker of azurophil granules. To determine the extended sequence specificity of recombinant NSP4, we used an iterative fluorescence resonance energy transfer–based optimization strategy. In total, 142 different peptide substrates with arginine in P1 and variations at the P1′, P2′, P3, P4, and P2 positions were tested. This enabled us to construct an α1-proteinase inhibitor variant (Ile-Lys-Pro-Arg−/−Ser-Ile-Pro) with high specificity for NSP4. This tailor-made serpin was shown to form covalent complexes with all NSP4 of neutrophil lysates and supernatants of activated neutrophils, indicating that NSP4 is fully processed and stored as an already activated enzyme in azurophil granules. Moreover, cathepsin C was identified as the activator of NSP4 in vivo, as cathepsin C deficiency resulted in a complete absence of NSP4 in a Papillon-Lefèvre patient. Our in-depth analysis of NSP4 establishes this arginine-specific protease as a genuine member of preactivated serine proteases stored in azurophil granules of human neutrophils.

AIM: Assessment of the effect of non-surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. METHODS: Overall, 31 ChP and 29 AgP were examined clinically prior to and 12 weeks after SRP (subgingival scaling of all pockets within 2 days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12 weeks after the first SRP visit. Serum elastase, C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed. RESULTS: At baseline, serum elastase, CRP, and LBP were significantly (p

Aim Comparison of regenerative therapy of infrabony defects with and without administration of postsurgical systemic doxycycline (DOXY). Methods In each of 61 patients one infrabony defect was treated with enamel matrix derivative (EMD), EMD plus filler or membrane at two centres. By random assignment patients received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery. Prior to and 6 months after surgery probing pocket depths (PPD) and vertical attachment level (PAL-V) were obtained. Results Fifty-four patients (DOXY: 27; PLAC: 27) were re-examined after 6 months and had been treated exclusively with EMD. Seven to 8 days after surgery 81% of defects in both groups showed complete flap closure. In both groups significant (p

This case report describes the clinical and microbiologic long-term outcome 5 years after periodontal therapy of two siblings diagnosed with Papillon-Lefèvre syndrome (PLS) and tinea capitis.In 2005, two brothers diagnosed with PLS and tinea capitis began periodontal treatment. Both of them showed premature mobility of the primary dentition, markedly increased probing depths, and subgingival Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans; Aa). Initial therapy consisted of scaling and root planing based on the concept of full-mouth disinfection, extraction of periodontally hopeless deciduous teeth, and systemic antibiotics. Reevaluation of clinical parameters revealed a dramatic improvement. After that, the patients were enrolled in a stringent maintenance program. Microbiologic monitoring was performed 1 and 5 years after treatment.Five years after initial treatment, the periodontal situation was stable in both patients. Residual deciduous teeth, with the exception of one tooth, could be retained and no further teeth were lost. Further disease progression on the previously involved teeth was controlled, and development of periodontitis on erupting teeth was prevented for a period of 5 years.Even periodontally affected deciduous teeth can be treated successfully in patients with PLS. Suppression of Aa and a stringent maintenance program are of high importance.

To measure directly the thickness of the palatal mucosa using sharp cannulas and to evaluate potential correlations with gender and body mass index (BMI).Thirty-three participants (19 women) 23 to 41 years of age (27.8 +/- 4.1) were examined. Mucosal thickness from maxillary left canine to left second molar was measured at defined sites under local anesthesia using single-use cannulas with silicone stops. The cannulas were evaluated on video images.The mean thickness of the palatal mucosa was lowest in the first molar areas (4.39 +/- 1.05 mm), increased considerably in the canine/premolar regions, and was highest in the second molar areas (5.75 +/- 1.78 mm). Women exhibited higher mucosal thickness values than men in all tooth regions (P.05 for the canine and the molar regions). Multivariate analysis revealed a relation of palatal mucosal thickness to gender and BMI.The thickness of the palatal mucosa is characterized by variations that correlate with tooth regions, gender, and BMI. Direct measurements with sharp cannulas provide higher thickness values than measurements with blunt periodontal probes or ultrasonographic measurements. This finding is important particularly with regard to the hard palate as a donor site for connective tissue grafts.

Aim: The autosomal-recessive Papillon-Lefevre syndrome (PLS) is characterized by severe aggressive periodontitis, combined with palmoplantar hyperkeratosis, and is caused by mutations in the Cathepsin C (CTSC) gene. This study aimed to identify CTSC mutations in different PLS phenotypes, including atypical forms and isolated pre-pubertal aggressive periodontitis (PAP). Material and Methods: Thirteen families with different phenotypes were analysed by direct sequencing of the entire coding region and the regulatory regions of CTSC. The function of novel mutations was tested with enzyme activity measurements. Results: In 11 of 13 families, 12 different pathogenic CTSC mutations were found in 10 typical PLS patients, three atypical cases and one PAP patient. Out of four novel mutations, three result in protein truncation and are thus considered to be pathogenic. The homozygous c.854C>T nucleotide exchange (p.P285L) was associated with an almost complete loss of enzyme activity. The observed phenotypic heterogeneity could not be associated with specific genotypes. Conclusions: The phenotypic variability of the PLS associated with an identical genetic background may reflect the influence of additional genetic or environmental factors on disease characteristics. CTSC mutation analyses should be considered for differential diagnosis in all children suffering from severe aggressive periodontitis.

Objective: Report of clinical and microbiological periodontal findings before and 6 months after treatment of two siblings with Papillon–Lefevre syndrome (PLS) and tinea capitis. Methods: Two brothers, RG 3 years and NG 5 years of age, were referred for treatment due to premature mobility of their deciduous teeth. Probing depths (PPD), attachment levels (PAL-V), and furcation involvements were examined clinically. Panoramic radiographs were taken. Subgingival plaque samples within the deepest pocket of each tooth were taken and analysed by real-time polymerase chain reaction (PCR) for Actinobacillus actinomycetemcomitans (AA), Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Fusobacterium nucleatum, and Prevotella intermedia. One-stage full-mouth scaling and extraction of hopeless teeth were performed under general anaesthesia, followed by systemic amoxicillin and metronidazole for 7 days. Clinical and microbiological analyses were performed 6 months after treatment. Results: Before treatment, both siblings had exhibited PPD of up to 13 mm, Class III furcation defects at four teeth, and marginal suppuration. AA was detected in both patients and at all teeth at levels ranging from 3.0 × 102 to 5.1 × 106. Both patients exhibited palmar and plantar hyperkeratosis. Seven teeth were extracted from RG, and nine from NG. Six months after treatment, PPD had been reduced to ≤5 mm. AA was not detected in any of the remaining teeth. Conclusion: Even periodontally affected deciduous teeth of PLS patients can be treated successfully. Suppression of AA to below detection level seems to be of high significance.

To evaluate the clinical effects of topical subgingival application of a doxycycline gel compared to conventional mechanical debridement in supportive periodontal therapy.37 patients with residual or recurring periodontitis after systematic periodontal treatment at two centers (Heidelberg, Frankfurt) participated in this study. They had to exhibit at least one single-rooted tooth with either a probing depth (PPD) = 5 mm and bleeding-on-probing (BOP) or with PPDor = 6 mm. The patients were randomly assigned to one of the two different treatment regimes: DOXY (exclusively subgingival application of a 14% doxycycline gel) or SRP (scaling and root planing with a sonic scaler). Clinical examinations (plaque index [P1I], PPD, vertical relative attachment level [RAL-V], gingival index [GI]) were performed before, 3, and 6 months after therapy.In 37 patients (19 female), aged 30-76 years with a total of 168 teeth were treated (DOXY: 79; SRP: 89). Six months after therapy, both groups exhibited statistically significant (P0.001) reductions of PPD (DOXY: -1.43 +/- 0.22 mm; SRP: -1.14 +/- 0.18 mm) and gains of RAL-V (DOXY: 0.79 +/- 0.22 mm; SRP: 0.72 +/- 0.19 mm). Multilevel regression analyses, considering the therapy of different numbers of teeth in different patients, failed to show statistically significant differences concerning PPD reduction and RAL-V gain between both therapies (DOXY/SRP). For both therapies, PPD reduction was significantly better in deeper pockets (PPDor = 7 mm) than in shallow pockets (PPD: 5-6 mm).

Background: Topical application of active substances offers an additional option in periodontal therapy. The aim of this study was to examine the influence of the administration of a novel, biodegradable 14% doxycycline gel on microbiological findings, in connection with scaling and root planing. Methods: One hundred ten patients in three centers (Frankfurt and Heidelberg, Germany; Nijmegen, The Netherlands) with moderate to advanced periodontitis were evaluated in this randomized, double-masked, split-mouth clinical trial. In each patient, three test teeth were randomly assigned to one of three treatment modalities: 1) scaling and root planing (SRP) alone; 2) SRP with subgingival placebo gel (VEH); or 3) SRP and 14% doxycycline gel (DOX). Subgingival plaque samples were analyzed at baseline and 3 and 6 months after therapy for Actinobacillus actinomycetemcomitans (A.a.), Tannerella forsythensis (T.f.), Porphyromonas gingivalis (P.g.), and Treponema denticola (T.d.) using a RNA probe. Samples from 10 patients were tested for resistance against doxycycline, amoxicillin/clavulanic acid, cefoxitin, clindamycin, and metronidazole using agar diffusion testing. Results: The largest decrease in pathogens was found after 3 months, with the most pronounced differences between DOX and SRP (P

With the help of so-called controlled release delivery systems, the half-life period of locally administered antibiotics in gingival crevicular fluid (GCF) can be extended significantly. The aim of this study was to characterize the delivery profile of a new one-component 14% doxycycline free amine gel for local application. Pharmacokinetics of doxycycline (DOXY) were analyzed in GCF, saliva, and serum.Twenty patients with persisting or recurring pockets (probing depthsor = 5 mm and bleeding on probing) after mechanical treatment (surgical or non-surgical) took part in the study. In each patient 1 periodontal defect was treated with DOXY gel. Samples of GCF, saliva, and serum were obtained before application of DOXY gel; 15 minutes after application; at 2 and 5 hours; and at 1, 2, 3, 4, 7, 9, and 11 days after application. Separation and quantitative measurement of DOXY was performed with high performance liquid chromatography and UV detection at lambda = 260 nm.Coefficients of variation were lower than 2% (intraassay) and 4% (interassay), respectively. For concentrations between 50 to 1000 microg/ml, we found a linear relationship between expected and measured DOXY values (linear coefficient of correlation: r = 0.998). Within the first 5 hours after application, concentration of DOXY in GCF (maximum after 15 minutes 19.97 +/- 5.85 mg/ml) and saliva (maximum after 15 minutes 17.83 +/- 2.84 mg/ml) was similar. Then concentration fell to a lower level (28.90 +/- 19.44 microg/ml) compared to GCF (577.41 +/- 127.34 microg/ml) after 3 days. Up to 10 days after application, the concentration of DOXY in GCF was 34.24 microg/ml. With the exception of 1 patient, all serum samples were DOXY-negative.1) After subgingival application of biodegradable 14% doxycycline gel, mean doxycycline levels in GCF that exceeded 16 microg/ml could be maintained for at least 12 days. Thus, the antimicrobial agent may be classified as a controlled release device. 2) The antibiotic effect was limited mainly to the subgingival sites of application of the doxycycline gel. 3) The doxycycline gel possesses the pharmacokinetic and clinical properties to deliver efficacious levels of antibiotics to the periodontal pocket and to maintain these levels for at least 1 week without the need of further drug retention by a periodontal dressing.

Evaluation of the clinical effect of topical application of doxycycline adjunctive to non-surgical periodontal therapy.A total of 111 patients suffering from untreated or recurrent moderate to severe periodontitis at 3 different centers (Heidelberg, Frankfurt, Nijmegen) were treated in this double-blind split-mouth study. In each patient, 3 different treatment modalities were assigned randomly to 3 test teeth: scaling and root planing alone (SRP), SRP with subgingival vehicle control (VEH), and SRP with subgingival application of a newly developed biodegradable 15% doxycycline gel (DOXI). At baseline, clinical parameters were measured at all single rooted teeth using a reference splint: PlI, PPD, relative attachment level (RAL-V), GI. 3 strata were generated according to baseline PPD: (i) 5-6 mm, (ii) 7-8 mm, (iii)or =9 mm. Not more than 50% active smokers were allowed to each stratum. 3 and 6 months after therapy re-examination was performed by examiners blinded to baseline data and test sites. The statistical comparison of RAL-V gain and PPD reduction between the treatments was based on a repeated measures ANOVA with correction according to HuynhFeldt. The comparison of SRP versus DOXI was considered as the main study question.110 patients finished the 3 months and 108 the 6 months examination. The study did not show adverse effects of VEH or DOXI except for one singular inflammation that occurred 2 months after application of the doxycycline gel. DOXI provided statistically significantly more favorable PPD reduction (SRP: -2.4+/-1.4 mm, VEH: -2.7+/-1.6 mm, DOXI: -3.1+/-1.2 mm; SRP versus DOXI p=0.0001, VEH versus DOXI p=0.0066) and RAL-V gain (SRP: 1.6+/-1.9 mm, VEH: 1.6+/-2.2 mm, DOXI: 2.0+/-1.7 mm; SRP versus DOXI p=0.027, VEH versus DOXI p=0.038) than SRP and VEH after 6 months.Adjunctive topical subgingival application of a biodegradable 15% doxycycline gel was safe and provided more favorable RAL-V gain and PPD reduction than SRP alone and VEH. Thus, by use of topical doxycycline the threshold for surgical periodontal therapy might be moved toward deeper pockets.

Melkersson-Rosenthal syndrome (MRS) is a rare granulomatous inflammatory disease characterised by the triad of orofacial oedema, facial nerve palsy and furrowed tongue. We describe the case of a 29-year-old patient suffering from an oligosymptomatic form of the disease with orofacial oedema, cobblestone pattern on the buccal mucosa and swelling of the tongue, accompanied by intermittent fatigue, influenza-like symptoms, intermittent tinnitus and acute hearing loss. An increase of several autoimmune-associated antibodies was also detected. Treatment with prednisolone, azathioprine or methotrexate failed to adequately control all symptoms in the long term. In the absence of a specific and well-established therapy for MRS, treatment with adalimumab was administered. Under adalimumab, total remission of all symptoms was achieved, indicating that tumour necrosis factor-α blockers are a promising therapeutic option for patients with Melkersson-Rosenthal syndrome.