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AIM: The autosomal-recessive Papillon-Lefèvre 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. [ABSTRACT FROM AUTHOR]

When ultrasonic disintegration of bacteria was employed to liberate intracellular beta-lactamases there was rapid and irreversible inactivation of the type-Id beta-lactamase from Pseudomonas aeruginosa. Various type-V beta-lactamases (PSE-2, 3 and 4) from P. aeruginosa, as well as Enterobacter cloacae type-Ia beta-lactamase were much less affected by sonication. None of the beta-lactamases was inactivated by French Press disruption. We suggest that French Press disruption should be the method of choice for the release of beta-lactamases, unless the enzyme in question is known to be unaffected by ultrasonic treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To measure directly the thickness of the palatal mucosa using sharp cannulas and to evaluate potential correlations with gender and body mass index (BMI). METHOD AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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. [ABSTRACT FROM AUTHOR]

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)., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

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.

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.

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.

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., (© 2020 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Membrane-bound proteinase 3 (PR3 m ) is the main target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis, a systemic small-vessel vasculitis. Binding of ANCA to PR3 m 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 PR3 m 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 PR3 m 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 PR3 m on PLS neutrophils, whereas the total amount of PR3 m 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 PR3 m , cellular PR3 protein, and proteolytic PR3 activity, whereas neutrophil differentiation was not compromised., (© 2018 Seren et al.)

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.

Background: Nonunion of the scaphoid as a result of proximal fractures, failed surgical reconstruction, and especially avascular fragment necrosis are possible indications of vascularized bone grafts. Various techniques of vascularized (pedicled and free) grafts have been described. Pedicled grafts from the direct vicinity of the wrist provide several benefits. Harvest-site morbidity is reduced and preserved graft perfusion, without the need for blood vessel anastomosis, may lead to an improved consolidation., Methods: A common pedicled vascularized bone graft for reconstruction of the scaphoid was first described by C. Zaidemberg and colleagues in 1991. We describe 49 consecutive patients, who underwent vascularized bone-grafting, pedicled on the 1.2 intercompartmental, supraretinacular artery in a modified technique based on Zaidemberg's description. The fixation of the bone graft was performed by Kirschner wires., Results: A consolidation was detected in 37 cases, and 9 cases showed a persistent nonunion (3 patients did not follow up). According to the classification of Herbert, 44 patients had a nonunion grade D2 or higher, of which 36 patients showed a bony consolidation (8 non-consolidated). Complications occurred in individual cases (1x intraoperative fracture of the radius, 4x transient irritations of the superficial branch of the radial nerve). A loss in the range of motion of the affected wrist was frequent. An indication for a pedicled graft was seen if the preoperative contrast-enhanced MRI showed an impaired perfusion of scaphoid fragments., Discussion: The more advanced the changes in MRI, the more frequently treatment failed. The vascularized bone graft from the dorsal distal radius described by C. Zaidemberg et al. is one of several ways to address a circulation-impaired nonunion of the scaphoid.

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., (© 2015 FEBS.)

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., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

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.

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.

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., (2014 BMJ Publishing Group Ltd.)

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.

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.

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.