Core continuing professional development (CPD) topics for the European dentist.

INTRODUCTION: In the context of free movement, EU-citizens need assurance that dental practitioners providing their care have a degree/license to practice that meets EU-standards and that they maintain their knowledge and skills through ongoing education. AIM: One aim of the 'DentCPD' project (HYPERLINK 'http://www.dentcpd.org' www.dentcpd.org) was to identify and agree essential CPD requirements for EU dentists. This paper reports the consensus process and outcomes. METHODS: Agreement on core components of CPD was achieved through a three stage process: an online survey of dental educators' (n = 143) views on compulsory topics; a paper-based questionnaire to practitioners (n = 411); leading to a proposal discussed at the Association for Dental Education (ADEE) 2011 Lifelong Learning special interest group (SIG). RESULTS: From the online survey and practitioner questionnaire, high levels of agreement were achieved for medical emergencies (89%), infection control (79%) and the medically compromised patient (71%). The SIG (34 attendees from 16 countries) concluded that these three CPD topics plus radiation protection should be core-compulsory and three CPD topics should be core-recommended (health and safety, pain management, and safeguarding children & vulnerable adults). They also agreed that the teaching of all topics should be underpinned by evidence-based dentistry. CONCLUSION: Building four core topics into CPD requirements and making quality-approved education and training available will ensure that all dentists have up-to-date knowledge and skills in topic areas of direct relevance to patient safety. In turn, this will contribute to patients having access to comparably high standards of oral health care across Europe.

Guidelines for the organisation of continuing professional development activities for the European dentist.

AIM: Free movement of dental professionals across the European Union calls for more uniform continuing education in dentistry to ensure up-to-date, high-quality patient care and patient safety. This article provides guidelines for the management and delivery of high-quality continuing professional development (CPD) by European dental schools and other CPD providers. METHOD: The guidelines are based on an extensive literature inventory, a survey of existing practices (both available as separate publications), discussions during meetings of the Association for Dental Education in Europe in 2011 and 2012 and debate amongst the members of the DentCPD project team representing six dental schools. RESULTS: On the basis of the literature review, survey and discussions, we recommend that (i) every dentist should be given the opportunity for CPD, (ii) providers should be quality-approved and impartial, (iii) educators should be approved, impartial, suitably trained, and with educational expertise, (iv) the mode of CPD delivery should suit the educational activity, with clear learning objectives or outcomes, (v) effort should be made to assess the learning, (vi) participant feedback should be collected and analysed to inform future developments and (vii) uniform use of the pan-European system of learning credit points (ECTS) should be implemented. CONCLUSION: Implementation of these guidelines should make dental CPD more transparent to all relevant parties and facilitate the transferability of earned credits across the European Union. It will also enable better quality control within dentistry, resulting in enhanced dental care and ultimately the improvement in patient safety.

Core continuing professional development (CPD) topics for the European dentist.

INTRODUCTION: In the context of free movement, EU-citizens need assurance that dental practitioners providing their care have a degree/license to practice that meets EU-standards and that they maintain their knowledge and skills through ongoing education. AIM: One aim of the 'DentCPD' project (HYPERLINK 'http://www.dentcpd.org' www.dentcpd.org) was to identify and agree essential CPD requirements for EU dentists. This paper reports the consensus process and outcomes. METHODS: Agreement on core components of CPD was achieved through a three stage process: an online survey of dental educators' (n = 143) views on compulsory topics; a paper-based questionnaire to practitioners (n = 411); leading to a proposal discussed at the Association for Dental Education (ADEE) 2011 Lifelong Learning special interest group (SIG). RESULTS: From the online survey and practitioner questionnaire, high levels of agreement were achieved for medical emergencies (89%), infection control (79%) and the medically compromised patient (71%). The SIG (34 attendees from 16 countries) concluded that these three CPD topics plus radiation protection should be core-compulsory and three CPD topics should be core-recommended (health and safety, pain management, and safeguarding children & vulnerable adults). They also agreed that the teaching of all topics should be underpinned by evidence-based dentistry. CONCLUSION: Building four core topics into CPD requirements and making quality-approved education and training available will ensure that all dentists have up-to-date knowledge and skills in topic areas of direct relevance to patient safety. In turn, this will contribute to patients having access to comparably high standards of oral health care across Europe.

Continuing professional development systems and requirements for graduate dentists in the EU: survey results from the DentCPD project.

INTRODUCTION: By maintaining skills and keeping dentists up-to-date, continuing professional development (CPD) supports safe clinical practice. However, CPD for dentists across Europe is not harmonised. AIM: One aim of the 'DentCPD' project (www.dentcpd.org) was to identify and agree essential CPD requirements for EU dentists. As part of the process, data were collected on existing approaches to CPD for EU dentists. This paper reports those findings. METHODS: Informed by a review of the literature and internet search, the CPD for Graduate Dentists questionnaire gathered data from dental educators on CPD systems, requirements, provision and accreditation in Europe. It sought opinion on mandatory CPD and e-learning. RESULTS: Responses were received from 143 individuals from 30 EU countries. About half the countries had a compulsory CPD system which typically included mandatory core topics. Elsewhere CPD was optional or based on recommended hours. University dental schools and professional dental associations were the most common CPD providers. National regulatory bodies were the most common accrediting body. Only 41% of respondents thought they knew the criteria for successful accreditation of CPD. Eighty-one percent agreed that 'CPD should be obligatory for all dentists'. CONCLUSION: These results present an overview of the status of CPD for EU dentists. Despite a notable trend towards regulated CPD systems, current requirements for dentists to engage in CPD show variation. The harmonisation of requirements would enhance both dentist mobility and safe clinical practice.

Continuing professional development systems and requirements for graduate dentists in the EU: survey results from the DentCPD project.

INTRODUCTION: By maintaining skills and keeping dentists up-to-date, continuing professional development (CPD) supports safe clinical practice. However, CPD for dentists across Europe is not harmonised. AIM: One aim of the 'DentCPD' project (www.dentcpd.org) was to identify and agree essential CPD requirements for EU dentists. As part of the process, data were collected on existing approaches to CPD for EU dentists. This paper reports those findings. METHODS: Informed by a review of the literature and internet search, the CPD for Graduate Dentists questionnaire gathered data from dental educators on CPD systems, requirements, provision and accreditation in Europe. It sought opinion on mandatory CPD and e-learning. RESULTS: Responses were received from 143 individuals from 30 EU countries. About half the countries had a compulsory CPD system which typically included mandatory core topics. Elsewhere CPD was optional or based on recommended hours. University dental schools and professional dental associations were the most common CPD providers. National regulatory bodies were the most common accrediting body. Only 41% of respondents thought they knew the criteria for successful accreditation of CPD. Eighty-one percent agreed that 'CPD should be obligatory for all dentists'. CONCLUSION: These results present an overview of the status of CPD for EU dentists. Despite a notable trend towards regulated CPD systems, current requirements for dentists to engage in CPD show variation. The harmonisation of requirements would enhance both dentist mobility and safe clinical practice.

The development of an exemplar e-module for the continuing professional development of European dentists.

AIM: To present the development of an exemplar e-module for dental continuing professional development (CPD) provided by dental schools and other dental educational providers. MATERIALS AND METHODS: The exemplar e-module covered the topic of 'Sterilisation and cross-infection control in the dental practice' as this is one of the most recommended topics for dental CPD in Europe. It was developed by a group of topic experts, adult learning and distance learning experts and a technical developer. Major concerns were pedagogy, interoperability, usability and cost reduction. Open-source material was used to reduce the cost of development. RESULTS: The e-module was pre-piloted in dental practitioners for usability and then evaluated by experts in the field and dental academics through an electronic questionnaire and an online presentation and discussion at the ADEE 2012 Special Interest Group on DentCPD-Lifelong learning. This facilitated refinement before final production. A Creative Commons License was implemented to ensure the developers' rights and facilitate wider distribution and access to CPD providers. DISCUSSION AND CONCLUSIONS: The e-module was developed according to well-defined pedagogical and technical guidelines for developing e-learning material for adult learners. It was structured to promote self-study by directing learners through their study, promoting interaction with the material, offering explanation and providing feedback. Content validity was ensured by extensive review by experts. The next step would be to expand the evaluation to practising dentists in various countries after relevant translations, and adaptations to local policies have been made.

Recommendations for the development of e-modules for the continuing professional development of European dentists.

AIMS: To provide evidence-based and peer-reviewed recommendations for the development of dental continuing professional development (CPD) learning e-modules. METHODS: The present recommendations are consensus recommendations of the DentCPD project team and were informed by a literature research, consultations from e-learning and IT expert, discussions amongst the participants attending a special interest group during the 2012 ADEE meeting, and feedback from the evaluation procedures of the exemplar e-module (as described in a companion paper within this Supplement). The main focus of these recommendations is on the courses and modules organised and offered by dental schools. RESULTS AND DISCUSSION: E-modules for dental CPD, as well as for other health professionals' continuing education, have been implemented and evaluated for a number of years. Research shows that the development of e-modules is a team process, undertaken by academics, subject experts, pedagogists, IT and web designers, learning technologists and librarians. The e-module must have clear learning objectives (outcomes), addressing the learners' individual needs, and must be visually attractive, relevant, interactive, promoting critical thinking and providing feedback. The text, graphics and animations must support the objectives and enable the learning process by creating an attractive, easy to navigate and interactive electronic environment. Technology is usually a concern for learners and tutors; therefore, it must be kept simple and interoperable within different systems and software. The pedagogical and technological proficiency of educators is of paramount importance, yet remains a challenge in many instances. CONCLUSIONS: The development of e-courses and modules for dental CPD is an endeavour undertaken by a group of professionals. It must be underpinned by sound pedagogical and e-learning principles and must incorporate elements for effective visual learning and visual design and a simple, consistent technology.

Effect of directorial intervention on web-based student feedback.

UNLABELLED: The Medical Faculty of the University of Helsinki decided to employ a web-based evaluation system as an integral and essential part of all courses beginning in the autumn term of 2006. OBJECTIVES: To analyse the effects of the intervention on dental students' web-based responses at the University of Helsinki, Finland. SUBJECTS AND METHODS: A previously developed web-based tool was used for all preclinical and clinical courses from the beginning of the 2006-2007 academic year. We analysed data sets of student feedback for all courses before (2005-2006) and after (2006-2007) the intervention. We then compared the quantity and quality of the students' feedback for the six standardised questions used in the evaluation, and calculated the means and standard deviations of values obtained with a Likert scale. The students' assessments in the open questions were categorised according to key issues. RESULTS: Implementation of the system resulted in a considerable increase in student feedback: the mean response rate for the preclinical phase rose from 59% (SD 15.0; range 25-80) before the intervention to 90% (SD 9.6; range 72-100) after it. In the clinical phase, the response rates more than doubled from 34% (SD 15.9; range 9-69) to 73% (SD 12.9; range 45-100). The students' assessments showed no significant change despite the marked rise in response rates. The educators' positive attitude towards the students was appreciated (4.2-4.3) whereas the general goals for the courses in the clinical phase seemed unclear to the students (3.4) (P < 0.05). CONCLUSIONS: Web-based evaluation as an integral part of all courses in the dental curriculum proved successful: shortly after the intervention, we observed a considerable increase in student feedback with no significant change in quality.

Dental findings in diabetic adults.

The dental status of dentate diabetic adults (n = 299) and its associations with diabetes-related factors was explored in Tehran, Iran. Presence of diabetes-related complications made no difference in mean values of DMFT, but was associated with a higher number of decayed and missing teeth, and fewer filled teeth. Higher level of HbA1c was associated with higher DMFT for men, but not for women. In conclusion, the results suggest a possible association between the level of metabolic control of diabetes mellitus and cumulative caries experience.

Gold sodium thiomalate activates latent human leukocyte collagenase.

Gold sodium thiomalate, a drug used widely in the therapy of rheumatoid arthritis, was found to be an activator of latent human polymorphonuclear leukocyte collagenase. The activation was demonstrated by two distinct and independent collagenase assays: by recording with a spectrophotometer at 227 nm the enzyme-induced increase in ultraviolet difference absorbance of native type I collagen connected to the cleavage of collagen at 37 degrees C [(1986) Eur. J. Biochem. 156, 1-4] and by SDS-polyacrylamide gel electrophoresis analysis of formation of specific products of collagen resulting from collagenase cleavage at 25 degrees C. Activation of latent collagenase by gold sodium thiomalate appeared to be of the same magnitude as by the known activator phenylmercuric chloride.

Collagenase in synovitis of rheumatoid arthritis.

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.

Latent human leukocyte collagenase can be activated by gold thioglucose and gold sodium thiomalate, but not by auranofin.

Gold thioglucose and gold sodium thiomalate were shown to be potent activators of latent human leukocyte collagenase. No activation by auranofin was noted. The activation may proceed through the action of gold on the essential sulfhydryl groups of latent enzyme and, thereby, mimick the action of the known organomercurial activators.

Tetracycline inhibition and the cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. A review article.

Tetracyclines have recently been shown to inhibit the activity of some but not all mammalian matrix metalloproteinases believed to mediate periodontal destruction. However, the specificity of this effect, which could have significant therapeutic implications for different periodontal diseases, has not been examined in detail. Doxycycline and 4-de-dimethylaminotetracycline (CMT-1) have been tested in vitro for their ability to inhibit human neutrophil and fibroblast interstitial collagenases and collagenase in human gingival crevicular fluid (GCF). The GCF samples were obtained from systemically healthy and insulin-dependent diabetic adult periodontitis patients and from localized juvenile periodontitis (LJP) patients. The concentrations of these 2 tetracyclines required to inhibit 50% of the collagenase activity (IC50) were found to be 15 to 30 microM for human neutrophil collagenase and for collagenase in GCF of systemically healthy and diabetic adult periodontitis patients. These concentrations approximate the tetracycline levels observed in vivo during treatment with these drugs. In contrast, human fibroblast collagenase and GCF collagenase from LJP patients were both relatively resistant to tetracycline inhibition; the IC50 for doxycycline and CMT-1 for these 2 sources of collagenase were 280 and 500 microM, respectively. Based on these and other findings, we propose the following: 1) that systemic levels of tetracycline may inhibit connective tissue breakdown by inhibiting neutrophil collagenase; 2) that tetracyclines do not inhibit fibroblast-type collagenase, which may help explain their lack of effect on normal connective tissue remodeling; 3) that tetracycline inhibition of collagenases may serve to identify the cellular origin of the enzyme; and 4) that tetracyclines can also prevent the oxidative activation of latent human procollagenases.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of gingival crevicular fluid and salivary interstitial collagenases in human periodontal diseases.

Interstitial collagenases (matrix metalloproteinase-1, EC 3.4.24.7), isolated from extracts of inflamed human gingiva, gingival crevicular fluid and saliva were characterized for their molecular weight, proteolytic and non-proteolytic activation and substrate specificity against soluble collagen types I, II and III. All three collagenases had Mr of 70 K. The enzymes existed predominantly in a latent form that could be activated by aminophenylmercuric acetate, gold thioglucose and hypochlorous acid. Among serine proteases tested, trypsin, chymotrypsin, neutrophil cathepsin G and a combination of trypsin and human gingival fibroblast prostromelysin activated gingival and salivary interstitial collagenases. Plasmin and plasma kallikrein, however, were relatively ineffective activators. The collagenases degraded soluble type I and II collagens at apparently equal rates but considerably faster than they did type III collagen. These findings suggest that the characteristics of interstitial collagenases found in inflamed human gingiva, gingival crevicular fluid and saliva are consistent with those of human neutrophil interstitial collagenase rather than the fibroblast-type interstitial collagenase. Thus, neutrophils are suggested to be the main source of such enzymes in inflamed human gingiva, crevicular fluid and saliva during adult periodontitis.

Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases.

Tetracyclines have recently been shown to inhibit the activity of mammalian matrix metalloproteinases, i.e. type I collagenase (MMP-1) and type IV collagenase/gelatinase (MMP-2). The specificity of this effect, however, has not been examined in detail. In the present study, doxycycline (a clinically widely used commercial tetracycline) and 4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial collagenases, which are distinct gene products, as well as collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic adult periodontitis patients. The concentrations of these two tetracyclines, required to inhibit 50% of the collagenase activity (IC50), were found to be 15-30 microM for purified human neutrophil collagenase as well as collagenase in gingival crevicular fluid of adult periodontitis patients and diabetic adult periodontitis patients, thus approximating in vivo therapeutic tetracycline levels. In contrast, the fibroblast collagenase and collagenase in gingival crevicular fluid of patients with juvenile periodontitis were relatively resistant to tetracycline inhibition: the IC50 for doxycycline and CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Reactive oxygen species as regulators of human neutrophil and fibroblast interstitial collagenases.

The effects of various reactive oxygen species on latent human neutrophil and fibroblast-type interstitial collagenases were studied. Latent human neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous acid and hydrogen peroxide and less efficiently by the serine proteinases trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate latent human neutrophil collagenase. The activation of latent human neutrophil collagenase by hypochlorous acid and hydrogen peroxide corresponded to the activation obtained with the other known non-proteolytic activators phenylmercuric chloride and gold thioglucose. The activation by hydrogen peroxide was inhibited by mannitol and desferoxamine, suggesting a localized Fenton-type reaction to be responsible for the generation of hydroxyl radical and/or hydroxyl radical-like reactive oxygen pathway of neutrophil procollagenase does not involve plasmin and plasma kallikrein, which are efficient proteolytic activators of latent fibroblast-type procollagenase (proMMP-1). Fibroblast procollagenase was also slightly activated by hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to prefer non-proteolytic means of activation and reactive oxygen species can be regarded as potent activators in vivo. Synovial-fluid neutrophils from rheumatoid arthritis patients were found to release collagenase in 30% active form when compared to same patients' peripheral blood neutrophils, which released collagenase in completely latent form. This may indicate that the triggering of neutrophil at the site of inflammation in vivo involves initial oxidative activation of collagenase upon the degranulation process.

Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases.

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8-specific chair-side test.

BACKGROUND AND OBJECTIVE: With current periodontal diagnostic tools it is difficult to identify susceptible individuals or sites at risk. The aim of this study was to evaluate the efficacy of the matrix metalloproteinase (MMP)-8-specific chair-side dip-stick test in longitudinally monitoring the periodontal status of smoking (S) and nonsmoking (NS) patients with chronic periodontitis, using their gingival crevicular fluid (GCF) MMP-8 concentrations. MATERIAL AND METHODS: Clinical parameters, MMP-8 test results and concentrations were monitored in 16 patients after initial treatment and in 15 patients after scaling and root planing (SRP), every other month, over a 12-mo time period. Progressing and stable sites, and sites with exceptionally high MMP-8 concentrations, were analysed in smokers and nonsmokers. RESULTS: SRP reduced the mean GCF MMP-8 levels, test scores, probing depth (PD), attachment loss (AL) and bleeding on probing (BOP). In sites of periodontal disease progression, the distribution of MMP-8 concentrations was broader than in stable sites, indicating a tendency for elevated concentrations in patients with periodontal disease. The mean MMP-8 concentrations in smokers were lower than in nonsmokers, but in smokers' and nonsmokers' sites with progressive disease, MMP-8 concentrations were similar. Sites with exceptionally elevated MMP-8 concentrations were clustered in smokers who also showed a poor response to SRP. In these sites, the MMP-8 concentration did not decrease with SRP and these sites were easily identified by the MMP-8 test. CONCLUSION: Persistently elevated GCF MMP-8 concentrations may indicate sites at risk, as well as patients with poor response to conventional periodontal treatment (e.g. SRP). MMP-8 testing may be useful as an adjunct to traditional periodontal diagnostic methods during the maintenance phase.

Relationship of collagenase and cathepsin G activity in gingival crevicular fluid.

Human neutrophil cathepsin G has been identified as a potent proteolytic activator of latent human neutrophil collagenase in vitro. In order to examine the role of cathepsin G in the activation mechanism of latent human neutrophil collagenase in vivo, gingival crevicular fluid was collected from periodontal pockets of patients with adult periodontitis and the relationship of cathepsin G to the proportion of endogenously active collagenase and total collagenase activity was determined. The changes in these parameters were monitored before and after periodontal therapy and compared to control values obtained for periodontal sites without clinical signs of inflammation or increased pocket depth. A significant decrease in cathepsin G and collagenase activity in gingival crevicular fluid collected from initially deep periodontal pockets was observed in response to scaling and root planing (P less than 0.025, Wilcoxon signed rank test). Also the proportion of endogenously active collagenase decreased (P less than 0.05). There was a significant correlation of cathepsin G and total collagenase activity. However, no correlation of cathepsin G activity and endogenously active collagenase was observed. The results indicate the existence of several distinct activation pathways for latent human neutrophil collagenase in vivo and suggest that, apart from cathepsin G, other proteolytic activation cascades and/or non-proteolytic activation pathways participate in the activation of latent human neutrophil collagenase in vivo.