The molecular machinery behind lysosome biogenesis and the maintenance of the perinuclear aggregate of late endocytic structures is not well understood. A likely candidate for being part of this machinery is the small GTPase Rab7, but it is unclear whether this protein is associated with lysosomes or plays any role in the regulation of the perinuclear lysosome compartment. Previously, Rab7 has mainly been implicated in transport from early to late endosomes. We have now used a new approach to analyze the role of Rab7: transient expression of Enhanced Green Fluorescent Protein (EGFP)-tagged Rab7 wt and mutant proteins in HeLa cells. EGFP-Rab7 wt was associated with late endocytic structures, mainly lysosomes, which aggregated and fused in the perinuclear region. The size of the individual lysosomes as well as the degree of perinuclear aggregation increased with the expression levels of EGFP-Rab7 wt and, more dramatically, the active EGFP-Rab7Q67L mutant. In contrast, upon expression of the dominant-negative mutants EGFP-Rab7T22N and EGFP-Rab7N125I, which localized mainly to the cytosol, the perinuclear lysosome aggregate disappeared and lysosomes, identified by colocalization of cathepsin D and lysosome-associated membrane protein-1, became dispersed throughout the cytoplasm, they were inaccessible to endocytosed molecules such as low-density lipoprotein, and their acidity was strongly reduced, as determined by decreased accumulation of the acidotropic probe LysoTracker Red. In contrast, early endosomes associated with Rab5 and the transferrin receptor, late endosomes enriched in the cation-independent mannose 6-phosphate receptor, and the trans-Golgi network, identified by its enrichment in TGN-38, were unchanged. These data demonstrate for the first time that Rab7, controlling aggregation and fusion of late endocytic structures/lysosomes, is essential for maintenance of the perinuclear lysosome compartment. INTRODUCTIONThe "kiss-and-run" model for lysosome biogenesis proposes that maintenance of the lysosomal compartment depends on continuous fusions of late endocytic structures accompanied by fission events (Storrie and Desjardins, 1996). This model implies that, in addition to heterotypic fusions between late endosomes and lysosomes in the perinuclear region, there could also be continuous exchange within the lysosomal vesicle population (homotypic fusion). Indeed, evidence for fusions and bidirectional traffic of soluble material between lysosomes and late endosomes has been reported (Jahraus et al., 1994;Mullock et al., 1994;van Deurs et al., 1995;Futter et al., 1996;Storrie and Desjardins, 1996;Bright et al., 1997;Mullock et al., 1998).Several different molecules are part of the machinery responsible for vesicle docking and fusion, Rab GTPases and SNAREs being among the best studied (Rothman and Warren, 1994;Denesvre and Malhotra, 1996;Pfeffer, 1996Pfeffer, , 1999Olkkonen and Stenmark, 1997;Mayer, 1999;Waters and Pfeffer, 1999). Rab proteins are important regulators of membrane traffic on the biosynthetic ...

The aim of the present review is to evaluate the English language literature regarding factors associated with the loss of oral implants. An evidence-based format in conjunction, when possible, with a meta-analytic approach is used. The review identifies the following factors to be associated with biological failures of oral implants: medical status of the patient, smoking, bone quality, bone grafting, irradiation therapy, parafunctions, operator experience, degree of surgical trauma, bacterial contamination, lack of preoperative antibiotics, immediate loading, nonsubmerged procedure, number of implants supporting a prosthesis, implant surface characteristics and design. Excessive surgical trauma together with an impaired healing ability, premature loading and infection are likely to be the most common causes of early implant losses. Whereas progressive chronic marginal infection (peri-implantitis) and overload in conjunction with the host characteristics are the major etiological agents causing late failures. Furthermore, it appears that implant surface properties (roughness and type of coating) may influence the failure pattern. Various surface properties may therefore be indicated for different anatomical and host conditions. Finally, the histopathology of implant losses is described and discussed in relation to the clinical findings.

The aim of this review was to offer a critical evaluation of the literature and to provide the clinician with scientifically-based diagnostic criteria for monitoring the implant condition. The review presents the current opinions on definitions of osseointegration and implant failure. Further, distinctions between failed and failing implants are discussed together with the presently used parameters to assess the implant status. Radiographic examinations together with implant mobility tests seem to be the most reliable parameters in the assessment of the prognosis for osseointegrated implants. On the basis of 73 published articles, the rates of early and late failures of Brånemark implants, used in various anatomical locations and clinical situations, were analyzed using a metanalytic approach. Biologically related implant failures calculated on a sample of 2,812 implants were relatively rare: 7.7% over a 5-year period (bone graft excluded). The predictability of implant treatment was remarkable, particularly for partially edentulous patients, who showed failure rates about half those of totally edentulous subjects. Our analysis also confirmed (for both early and late failures) the general trend of maxillas, having almost 3 times more implant losses than mandibles, with the exception of the partially edentulous situation which displayed similar failure rates both in upper and lower jaws. Surgical trauma together with anatomical conditions are believed to be the most important etiological factors for early implant losses (3.60% of 16,935 implants). The low prevalence of failures attributable to peri-implantitis found in the literature together with the fact that, in general, partially edentulous patients have less resorbed jaws, speak in favour of jaw volume, bone quality, and overload as the three major determinants for late implant failures in the Brånemark system. Conversely, the ITI system seemed to be characterized by a higher prevalence of losses due to peri-implantitis. These differences may be attributed to the different implant designs and surface characteristics. On the basis of the published literature, there appears to be a number of scientific issues which are yet not fully understood. Therefore, it is concluded that further clinical follow-up and retrieval studies are required in order to achieve a better understanding of the mechanisms for failure of osseointegrated implants.

In the present animal experiment, analyses and comparisons were made between the structure and composition of clinically healthy supraalveolar soft tissues adjacent to implants and teeth. 5 beagle dogs were used. The right mandibular premolar region was selected in each dog for placement of titanium implants, while the left mandibular premolar region served as control. Extractions of the mandibular premolars were preformed, healing allowed, following which titanium fixtures were installed in the edentolous premolar region. Abutment connection was carried out 3 months later. After another 2 months of healing, plaque control was initiated and maintained for 8 weeks. At the end of the plaque control period, clinical examinations were performed and biopsies harvested from the implant site and the contralateral premolar tooth region. Following fixation and decalcification, all tissue samples were embedded in EPON and examined by histometric and morphometric means. The result from the analyses demonstrated that the periimplant mucosa which formed at titanium implants following abutment connection had many features in common with gingival tissue at teeth. Thus, like the gingiva, the peri-implant mucosa established a cuff-like barrier which adhered to the surface of the titanium abutment. Further, both the gingiva and the peri-implant mucosa had a well-keratinized oral epithelium which was continuous with a junctional epithelium that faced the enamel or the titanium surface. In the periimplant mucosa, the collagen fibers appeared to commence at the marginal bone and were parallel with the abutment surface. All gingival and periimplant units examined were free from infiltrates of inflammatory cells. It was suggested that under the conditions of study, both types of soft tissues, gingiva and periimplant mucosa, have a proper potential to prevent subgingival plaque formation.

Guided bone regeneration (GBR) is commonly used in combination with the installment of titanium implants. The application of a membrane to exclude non‐osteogenic tissues from interfering with bone regeneration is a key principle of GBR. Membrane materials possess a number of properties which are amenable to modification. A large number of membranes have been introduced for experimental and clinical verification. This prompts the need for an update on membrane properties and the biological outcomes, as well as a critical assessment of the biological mechanisms governing bone regeneration in defects covered by membranes. The relevant literature for this narrative review was assessed after a MEDLINE/PubMed database search. Experimental data suggest that different modifications of the physicochemical and mechanical properties of membranes may promote bone regeneration. Nevertheless, the precise role of membrane porosities for the barrier function of GBR membranes still awaits elucidation. Novel experimental findings also suggest an active role of the membrane compartment per se in promoting the regenerative processes in the underlying defect during GBR, instead of being purely a passive barrier. The optimization of membrane materials by systematically addressing both the barrier and the bioactive properties is an important strategy in this field of research.