Therapeutic targeting of cathepsin C::from pathophysiology to treatment

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials

Penetration depths with an ultrasonic mini insert compared with a conventional curette in patients with periodontitis and in periodontal maintenance

Aim: The aim of the study was to test whether a slim Ultrasonic Tip reaches a more apical position when penetrating a periodontal pocket compared with the working blade of a conventional Gracey Curette in both untreated periodontitis and periodontal maintenance patients. Material and Methods: Twenty untreated and 15 periodontal maintenance patients were selected based on the presence of at least one site a pocket of >= 5 mm in each quadrant. Recordings were made at the four approximal sites of four experimental teeth in each patient. First, the probing pocket depth was measured with the Jonker Probe((R)). Second in randomized order, the penetration depth was assessed with an EMS PS Ultrasonic Tip and a Gracey Curette. Results: In the periodontitis group, the Ultrasonic Tip penetrated significantly deeper than the Jonker Probe and the Gracey Curette. In the maintenance group, no differences were observed. Comparing the penetration of the instruments between groups, as related to the Jonker Probe measurements, only in the periodontitis group did the Ultrasonic Tip reach a significantly more apical level. Conclusions: The results of the present study show that in untreated periodontitis patients, the Ultrasonic Tip penetrated the pocket deeper than the pressure-controlled probe and the Gracey Curette

Cyclosporin-induced gingival overgrowth: a clinical-epidemiological evaluation of 121 Italian renal transplant recipients

Background: Although other immunosuppressive agents have been recently introduced (e.g., tacrolimus), it has been calculated that in the next decade about 1 million people will still be taking cyclosporin (CsA). The association between gingival overgrowth (GO) and the use of CsA is still not clear. In the present study we evaluated the prevalence and the degree of GO in a group of Italian renal transplant patients and the possible relationship between gingival lesions and demographic, oral, systemic, and pharmacological variables. Methods: One hundred twenty-one renal transplant recipients receiving immunosuppressive therapy with CsA were evaluated in this study. Patients were classified in two groups. In the first (screening group), we included all those patients referred by the Parma University Renal Transplant Center for a general oral checkup, with no specific indications for GO. The second group (non-screening group) included all those patients who specifically had been referred to the Oral Pathology and Oral Medicine Unit because of GO. We considered the following variables: gender, daily CsA dose, duration of immunosuppressive treatment, CsA plasma concentration, concomitant use of another immunosuppressive agent (azathioprine), use of other GO inducers (calcium channel blockers, anti-epileptic drugs), oral hygiene scores, and other drugs taken at the time of oral examination. Results: Fisher’s exact test and chi square test demonstrated that in the screening group, duration of immunosuppressive treatment and oral hygiene scores were associated both with the prevalence and the high GO scores (P1 DIT <0.0001; P2 DIT = 0.0023; P1 hyg = 0.0084; P2 hyg = 0.0068). In the screening group, concomitant use of CsA and azathioprine is related to a low development degree of GO (P = 0.0088). In the non-screening group, we found a significant association between poor oral hygiene and high degree of GO (P = 0.0349). Conclusion: In addition to a probable genetic predisposition, duration of immunosuppressive treatment and oral hygiene status are the most important variables related to development and degree of GO during the use of CsA in this study