Long-term stability of infrabony defects treated with enamel matrix derivative alone: A retrospective two-centre cohort study.

AIM: To assess the long-term stability of attachment gain in infrabony defects (IBDs) 10 years after regenerative treatment with an enamel matrix derivative (EMD) alone. MATERIALS AND METHODS: Two centres (Frankfurt [F] and Heidelberg [HD]) invited patients for re-examination 120 ± 12 months after regenerative therapy. Re-examination included clinical examination (periodontal probing depths (PPD), vertical clinical attachment level (CAL), plaque index (PlI), gingival index (GI), plaque control record, gingival bleeding index and periodontal risk assessment) and review of patient charts (number of supportive periodontal care [SPC] visits). RESULTS: Both centres included 52 patients (29 female; median baseline age: 52.0 years; lower/upper quartile: 45.0/58.8 years; eight smokers), each contributing one IBD. Nine teeth were lost. For the remaining 43 teeth, regenerative therapy showed significant CAL gain after 1 year (3.0; 2.0/4.4 mm; p < .001) and 10 years (3.0; 1.5/4.1 mm; p < .001) during which CAL remained stable (-0.5; -1.0/1.0 mm; p = 1.000) after an average SPC of 9 years. Mixed-model regression analyses revealed a positive association of CAL gain from 1 to 10 years with CAL 12 months post operation (logistic: p = .01) as well as a higher probability for CAL loss with an increasing vertical extent of a three-walled defect component (linear: p = .008). Cox proportional hazard analysis showed a positive association between PlI after 12 months and tooth loss (p = .046). CONCLUSION: Regenerative therapy of IBDs showed stable results over 9 years. CAL gain is associated with CAL after 12 months and decreasing initial defect depth in a three-walled defect morphology. Tooth loss is associated with PlI 12 months post operation. CLINICAL TRIAL NUMBER: DRKS00021148 (URL: https://drks.de).

Effect of Subgingival Instrumentation on Neutrophil Elastase and C-Reactive Protein in Grade B and C Periodontitis: Exploratory Analysis of a Prospective Cohort Study.

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.

Long-Term Results after Placing Dental Implants in Patients with Papillon-Lefèvre Syndrome: Results 2.5-20 Years after Implant Insertion.

AIM: A retrospective evaluation of patients with Papillon-Lefèvre syndrome (PLS) treated with dental implants to identify factors that may influence treatment outcomes. METHODS: All PLS patients with dental implants currently registered at the Department of Periodontology, Goethe-University Frankfurt (20-38 years; mean: 29.6 years), were recruited. Five patients from three families (two pairs of siblings) with a total of 48 dental implants (inserted in different dental institutions) were included with a follow-up time of 2.5-20 years (mean: 10.4 years). RESULTS: Implant failure occurred in three patients (at least 15 implants). Nearly all patients demonstrated peri-implantitis in more or less advanced stages; 60% of patients demonstrated bone loss ≥50% around the implants. Two patients did not follow any supportive therapy. CONCLUSIONS: Implants in PLS patients who did not follow any maintenance programme had a high risk of peri-implantitis and implant loss.

Ten-Year Stability of Clinical Attachment after Regenerative Treatment of Infrabony Defects and Controls.

BACKGROUND: A similar long-term stable clinical attachment level (CAL) of infrabony defects (IBDs) after regenerative treatment compared to control teeth would indicate a high level of stability resulting from the regenerative approach. METHODS: Patients with a regeneratively treated IBD were screened 120 ± 12 months postoperatively for eligibility for study participation, and were included if complete baseline and 12-month examinations (plaque (PlI), periodontal probing depth (PPD), CAL) were available and a respective control tooth could be identified. Re-examination included clinical examination (PPD, CAL, PlI/GI, bleeding on probing, plaque control record, gingival bleeding index). RESULTS: A total of 27 patients (16 females; age (median; lower/upper quartile): 57.0; 44.0/60.0 years; 6 smokers) contributed 27 IBDs (test), for each of which a control tooth was identified. Five test teeth (18.5%) were lost between 12 and 120 months. The remaining 22 test teeth revealed a significant CAL gain after 1 (2.5 mm; 1.0/4.0 mm, p < 0.0001) and 10 (2.5 mm; 0.5/3.5 mm, p < 0.0001) years, whereas control teeth were stable (1 year: 0.0 mm; 0.0/1.0 mm, p = 0.396; 10 years: 0.0 mm; -1.0/1.5 mm, p = 0.215). The study did not detect any significant CAL change between 1 and 10 years for test (-0.5 mm; -1.0/0.5 mm, p = 0.414) and control teeth (0.0 mm; -1.0/1.0 mm, p = 0.739). In 15 patients, test and control teeth revealed stable CAL values between 12 and 120 months. CONCLUSION: Regenerative treatment of IBDs exhibited stability comparable to non-surgically treated, periodontally reduced sites over a 10-year period.

Retrospectively analysed tooth loss in periodontally compromised patients: Long-term results 10 years after active periodontal therapy-Patient-related outcomes.

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 < .001). Smoking, baseline severity of periodontitis, non-adherent SPT, positive interleukin-1 polymorphism, marital and educational status, private insurance, older age at baseline and BOP, small number of SPT were identified as patient-related risk factors for TL (P < .05). CONCLUSION: During 120 ± 12 months of SPT, only a small number of teeth was lost in periodontally compromised patients showing the positive effect of a well-established periodontal treatment concept. The remaining risk for TL should be considered using risk-adopted SPT allocation.

Effect of nonsurgical periodontal therapy on haematological parameters in grades B and C periodontitis: an exploratory analysis.

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 < 0.05). Using univariate analysis, MCV was noticeably lower in CP than BP at all examinations, HCT only at baseline. For CP, MCHC was noticeably higher 12 weeks after SD than at baseline and 1 day (p ≤ 0.005) and Hsp27 increased noticeably at 1 day (p < 0.05). Repeated measures analysis of variance revealed African origin to be associated with lower MCV and female sex with lower MCHC. 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.

Five-year stability of clinical attachment after regenerative treatment of infrabony defects compared to controls.

AIM: To evaluate the stability of attachment achieved in infrabony defects by regenerative treatment over 60 ± 12 months compared to control teeth. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Consequences of cathepsin C inactivation for membrane exposure of proteinase 3, the target antigen in autoimmune vasculitis.

Membrane-bound proteinase 3 (PR3m) is the main target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis, a systemic small-vessel vasculitis. Binding of ANCA to PR3m triggers neutrophil activation with the secretion of enzymatically active PR3 and related neutrophil serine proteases, thereby contributing to vascular damage. PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis. We first studied neutrophilic PR3 from 24 patients with Papillon-Lefèvre syndrome (PLS), a genetic form of CatC deficiency. PLS neutrophil lysates showed a largely reduced but still detectable (0.5-4%) PR3 activity when compared with healthy control cells. Despite extremely low levels of cellular PR3, the amount of constitutive PR3m expressed on the surface of quiescent neutrophils and the typical bimodal membrane distribution pattern were similar to what was observed in healthy neutrophils. However, following cell activation, there was no significant increase in the total amount of PR3m on PLS neutrophils, whereas the total amount of PR3m on healthy neutrophils was significantly increased. We then explored the effect of pharmacological CatC inhibition on PR3 stability in normal neutrophils using a potent cell-permeable CatC inhibitor and a CD34+ hematopoietic stem cell model. Human CD34+ hematopoietic stem cells were treated with the inhibitor during neutrophil differentiation over 10 days. We observed strong reductions in PR3m, cellular PR3 protein, and proteolytic PR3 activity, whereas neutrophil differentiation was not compromised.

Long-Term Stability After Regenerative Treatment of Infrabony Defects: A Retrospective Case Series.

BACKGROUND: This study aims to evaluate long-term stability of attachment achieved in infrabony defects (IBDs) by regenerative treatment. METHODS: 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. RESULTS: Regenerative therapy resulted in significant attachment gain after 1 (median: -3 mm, lower/upper quartile: -1.5/-4 mm; P <0.001) and 5 (median: -3 mm, lower/upper quartile: -1.9/4.5 mm; P <0.001) 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 PD >6 mm at 5-year reexamination are correlated with CAL-V loss from 1 to 5 years after surgery. CONCLUSIONS: 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.

Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome.

Papillon-Lefèvre 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.

Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles.

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.

Subgingival plaque sampling after combined mechanical and antibiotic nonsurgical periodontal therapy.

AIM: This study aimed to make a comparison of two sampling strategies of subgingival plaque after combined mechanical-antibiotic periodontal therapy. METHODS: Thirty patients (18 female) suffering from aggressive (n = 12) or generalised severe chronic (n = 18) periodontitis were included. Aggregatibacter actinomycetemcomitans had been detected subgingivally in all prior to anti-infective therapy (AT) and combined mechanical-antibiotic AT had been rendered. After AT clinical examinations were performed and subgingival plaque was sampled from the same four sites as prior to AT (ASPRE) as well as from the four deepest sites after AT (DEEP). Per patient two pooled samples (ASPRE/DEEP) were generated and analysed for A. actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola using a commercial 16S rRNA test. RESULTS: ASPRE failed to detect A. actinomycetemcomitans, DEEP detected A. actinomycetemcomitans only in two patients (7 %). Only for T. forsythia DEEP (53 %) provided higher detection frequencies than ASPRE (27 %; p = 0.005). Detection frequencies of P. gingivalis and T. denticola ranged from 47 to 53 %. CONCLUSION: After combined mechanical-antibiotic AT sampling the deepest sites revealed higher detection rates. Combined mechanical-antibiotic AT suppresses A. actinomycetemcomitans to a higher extent than P. gingivalis, T. forsythia and T. denticola.

Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.

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.

An extraordinary form of the Melkersson-Rosenthal syndrome successfully treated with the tumour necrosis factor-α blocker adalimumab.

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.

Clinical results after nonsurgical therapy in aggressive and chronic periodontitis.

AIM: This study aims to analyze factors influencing treatment results in aggressive (AgP) and chronic (ChP) periodontitis. METHODS: 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. RESULTS: 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. CONCLUSION: Regarding PPD reduction, AgP responded less favorably to nonsurgical treatment than ChP.

Enamel matrix derivative in propylene glycol alginate for treatment of infrabony defects with or without systemic doxycycline: 12- and 24-month results.

BACKGROUND: This aim of this study is to compare regenerative therapy of infrabony defects with and without administration of post-surgical systemic doxycycline (DOXY) 12 and 24 months after therapy. METHODS: In each of 57 patients, one infrabony defect (depth ≥ 4 mm) was treated regeneratively using enamel matrix derivative at two centers (Frankfurt am Main and Heidelberg). By random assignment, patients received either 200 mg DOXY per day or placebo (PLAC) for 7 days after surgery. Twelve and 24 months after surgery, clinical parameters (probing depths [PDs] and vertical clinical attachment level [CAL-V]) and standardized radiographs were obtained. Missing data were managed according to the last observation carried forward. RESULTS: Data of 57 patients (DOXY: 28; PLAC: 29) were analyzed (26 males and 31 females; mean age: 52 ± 10.2 years; 13 smokers). In both groups, significant (P <0.01) PD reduction (DOXY: 3.7 ± 2.2 mm; PLAC: 3.4 ± 1.7 mm), CAL-V gain (DOXY: 2.7 ± 1.9 mm; PLAC: 3.0 ± 1.9 mm), and bone fill (DOXY: 1.6 ± 2.7 mm; PLAC: 1.8 ± 3.0 mm) were observed 24 months after surgery. However, the differences between both groups failed to be statistically significant (PD: P = 0.574; CAL-V: P = 0.696; bone fill: P = 0.318). CONCLUSIONS: Systemic DOXY, 200 mg/day for 7 days, after regenerative therapy of infrabony defects did not result in better PD reduction, CAL-V gain, or radiographic bone fill compared with PLAC 12 and 24 months after surgery, which may be attributable to low power and, thus, random chance.

NSP4 is stored in azurophil granules and released by activated neutrophils as active endoprotease with restricted specificity.

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.

Long-term results after treatment of periodontitis in patients with Papillon-Lefèvre syndrome: success and failure.

AIM: Retrospective evaluation of periodontal status in patients with Papillon-Lefèvre syndrome (PLS) observed for ≥10 years; identification of factors that may influence treatment outcome; and reporting of the outcome of dental implants in four PLS patients. METHODS: All PLS patients currently registered at the Department of Periodontology, Goethe-University Frankfurt with a follow-up ≥10 years (13-33 years; mean 22 years) were recruited. Eight patients (aged 17-46 years) from five families (three pairs of siblings) were included. RESULTS: After comprehensive periodontal therapy in eight PLS patients, teeth were retained in only two. In six patients, all teeth were extracted, almost entirely due to periodontal reasons. In four patients, teeth were prosthodontically restored with implants. Currently, three patients already show peri-implantitis. CONCLUSIONS: In some PLS patients, periodontitis may be arrested by: combined mechanical and antibiotic periodontal treatment; extraction of severely diseased teeth; oral hygiene instructions; intensive maintenance therapy; and microbiological monitoring and treatment of the infection with Aggregatibacter actinomycetemcomitans. Implants in PLS patients who did not follow any maintenance programme have a high risk of peri-implantitis and implant loss. Treatment of PLS patients has always to be considered as high-risk cases.

Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis.

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 < 0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL-6 were significantly (p < 0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p < 0.001). A significant difference was observed regarding change of serum elastase 12 weeks after SRP between AgP and ChP (p = 0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth. CONCLUSION: SRP results in serum elastase reduction in AgP but not in ChP.

Regenerative therapy of infrabony defects with or without systemic doxycycline. A randomized placebo-controlled trial.

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 < 0.001) PPD reduction (DOXY: 3.87 ± 1.44 mm; PLAC: 3.67 ± 1.30 mm) and PAL-V gain (DOXY: 3.11 ± 1.50 mm; PLAC: 3.32 ± 1.83 mm) were observed. However, the differences failed to be statistically significant (PPD: 0.20; p = 0.588; PAL-V: 0.21; p = 0.657). CONCLUSIONS: Two hundred milligram systemic DOXY administered for 7 days after therapy of infrabony defects with EMD failed to result in better PPD reduction and PAL-V gain compared with PLAC which may be due to low power (50%) and, thus, random chance.