bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendritic cells and fungi
Authors: BUENTKE EVA , SCHEYNIUS ANNIKA
Published: September 2003

Fungi comprise a group of microorganisms that in the past 20 years has become increasingly important as a cause of human disease. Few fungi are professional but instead opportunistic pathogens, and some fungi can even act as allergens. Dendritic antigen‐presenting cells function as a link between innate and adaptive immunity and are therefore important in recognition of pathogens. Effective defense requires the host to discriminate between different pathogens to induce an appropriate response. Signaling from different groups of microbes can be mediated via the Toll‐like receptors (TLRs), leading to activation of conserved host defense signaling pathways that control the expression of a variety of immune response genes. Different dendritic cells (DCs) express different patterns of recognition molecules, which indicate that they are more or less efficient when responding to certain pathogens. DCs have an important role in the induction of cell‐mediated immune responses to fungi, and the studies reviewed here show that fungi, or possibly fungi‐derived factors, provide a powerful activation stimulus to DCs, resulting in DC maturation with upregulation of co‐stimulatory molecules and production of cytokine patterns leading to different T cell responses. The possibility of using ex vivo‐generated DCs as therapeutic tools for restoring anti‐fungal immunity is a challenge for the future.
Radiographic bone density around immediately loaded oral implants
Authors: Barone Antonio , Covani Ugo , Cornelini Roberto , Gherlone Enrico
Published: September 2003

Abstract: Objectives: The aim of this study was to analyze the bone density around immediately loaded oral implants by a new volumetric CT scan (Maxiscan) and to compare it with that of unloaded implants.

Material and methods: Four patients with an age range from 44 to 65 years old were selected for this study. All the patients needed a prosthetic rehabilitation in partially edentulous posterior maxillas or mandibles. A total of 12 oral implants were placed in the four patients. Six of these implants were immediately loaded while six were left unloaded. Six months after placement, immediately loaded and unloaded oral implants were analyzed by a volumetric CT scan.

Results: The overall success rate in this study with immediately loaded oral implants was 100%. The radiological assessments showed that the mean densitometric profile, which is a measure of bone mineralization, was higher in the immediately loaded group than in the unloaded group. The differences observed between the two groups of oral implants (immediately loaded and unloaded) were statistically significant (P<0.05). The bone was significantly more dense around immediately loaded than unloaded oral implants on the basis of a radiological assessment.

Conclusion: The innovative aspect of this clinical study is to propose a new method to analyze the bone density, reducing the need for histological analysis from human biopsy.
Healing and osseointegration of submerged microtextured oral implants
Authors: Oh Tae‐Ju , Yoon Joongkyo , Meraw Stephen J. , Giannobile William V. , Wang Hom‐Lay
Published: September 2003

Abstract: The success of dental implants is primarily dependent upon the degree of osseointegration or bone‐to‐implant contact (BIC), possibly facilitated by a roughened implant surface. This study was performed to histologically evaluate the nature of osseointegration and bone healing of submerged microtextured implants in eight dogs. Three months following tooth extraction in the posterior mandibulae, three microtextured submerged implants were placed in each quadrant. Block biopsies were harvested at 4 and 16 weeks (four dogs each) following surgery, and histologic preparation was performed. Histomorphometric analysis demonstrated that % BIC value increased marginally from 40% at 4 weeks to 48% at 16 weeks, without a statistically significant difference. The first bone‐to‐implant contact (f‐BIC) at 16 weeks was significantly lower than the 4‐week f‐BIC (0.81 mm vs. 0.56 mm). In conclusion, this study found minimal change in BIC over time (from 4 to 16 weeks) in unloaded microtextured implants, while the mean f‐BIC value significantly increased during this same observation period.
Anorganic porous bovine‐derived bone mineral (Bio‐Oss®) and ePTFE membrane in the treatment of peri‐implantitis in cynomolgus monkeys
Authors: Schou Søren , Holmstrup Palle , Jørgensen Torben , Skovgaard Lene Theil , Stoltze Kaj , Hjørting‐Hansen Erik , Wenzel Ann
Published: September 2003

Abstract: The purpose of the present study was to evaluate the effect of anorganic porous bovine‐derived bone mineral (Bio‐Oss®) and expanded polytetrafluoroethylene (ePTFE) membrane in the treatment of peri‐implantitis. A total of 64 implants with a titanium plasma‐sprayed (TPS) surface was inserted in eight cynomolgus monkeys (Macaca fascicularis). After a 3‐month healing period with plaque control, experimental peri‐implantitis characterized by a bone loss of 4–6 mm was induced during a period of 9–18 months. Surgical treatment involving Bio‐Oss+membrane, Bio‐Oss, membrane, or a conventional flap procedure (control) only was carried out. The animals were sacrificed six months after treatment. Evaluation by clinical parameters, radiography including quantitative digital subtraction radiography, histology, and stereology demonstrated healthy peri‐implant tissue irrespective of the applied surgical procedure. However, the amount of re‐osseointegration and the total amount of bone (Bio‐Oss and regenerated bone) were significantly higher in defects treated with membrane‐covered Bio‐Oss as compared with the other three treatment procedures. A mean bone‐to‐implant contact of 36% was obtained within defects treated with membrane‐covered Bio‐Oss. The corresponding values for the three other treatment procedures were 13–23%. The Bio‐Oss particles were in general highly integrated within the regenerated bone, but the particles in the occlusal part of the defects were entirely surrounded by connective tissue irrespective of membrane coverage. The present study demonstrates that surgical treatment involving Bio‐Oss covered by an ePTFE membrane is a useful treatment modality of experimental peri‐implantitis around implants with a TPS surface in cynomolgus monkeys. However, the treatment outcome is not as encouraging as seen with membrane‐covered autogenous bone graft particles documented in a study with same experimental design.
Representative marketing‐oriented study on implants in the Austrian population. I. Level of information, sources of information and need for patient information
Authors: Tepper Gabor , Haas Robert , Mailath Georg , Teller Christoph , Zechner Werner , Watzak Georg , Watzek Georg
Published: September 2003

Abstract: The number of dental implants inserted annually worldwide has been estimated to come close to a million. But the level of information available to patients about realistic, evidence‐based treatment options by implants is often enough more than fragmentary, and what is disseminated by the media and the industry does not always reflect evidence‐based empirical data. This survey of 1000 adults presented with 18 questions was designed to shed light on several points. These were (1) level of subjective patient information, (2) sources of information and prejudices, (3) future demand for implant treatment and target groups for patient information campaigns, and (4) potential misinformation, information deficits, discrepancies of information and how these come about. Of those questioned, 20% said unprompted that implants were a possibility to replace missing teeth. When prompted, 72% said that they knew about dental implants. Most of those questioned felt poorly informed about the options for replacing missing teeth and many knew less about implants than about other alternatives. The dentist was said to be the desired source of information, but 77% of those questioned reported that their dentists did not practice implant dentistry. More than 79% of those questioned did not know whether their dentist worked with implants. Forty‐four percent thought that implants should only be placed by specially trained doctors. Sixty‐one percent were of the opinion that dentists who provide implant dentistry were better qualified than their nonimplanting colleagues. Half of those questioned attributed implant failures to allergies and incompatibilities, the other half to poor medical care. Only 29% incriminated poor oral hygiene as a cause of implant failure. Future strategies should be geared to more professional public relations and patient information. Internationally operating qualified implant institutions could contribute much to balance discrepant information.
Representative marketing‐oriented study on implants in the Austrian population. II. Implant acceptance, patient‐perceived cost and patient satisfaction
Authors: Tepper Gabor , Haas Robert , Mailath Georg , Teller Christoph , Bernhart Thomas , Monov Gabriel , Watzek Georg
Published: September 2003

Abstract: Oral implantology is an established subspecialty of restorative dental and oral surgery. While an extensive body of evidence on the fundamentals of osseointegration and associated factors has been published, marketing‐oriented analyses based on representative public opinion polls of implant acceptance, patient‐perceived cost and patient satisfaction are scarce. In this study, an attempt was made to address these points by questioning a representative sample of 1000 adults in the household setting.

The interviewees were presented with 14 questions. Of those familiar with implants as one of the treatment alternatives, 61% reported they would accept implants if the need arose. Implant acceptance was highest among males and interviewees below the age of 30 years. The interest in implants increased with increasing family incomes. Four percent of those questioned already had implants. Twenty‐five percent knew someone who had undergone implant treatment. All those questioned found implant‐supported rehabilitation to be very expensive. Many of them blamed the dentists for the high cost. One detail was particularly evident: satisfaction among implanted patients was clearly higher than satisfaction rates perceived by them from what they were told about implants by others. First‐hand experiences with implants proved to be less biased than reported second‐hand information.
Influence of preimplant surgical intervention and implant placement on bone wound healing
Authors: Slotte Christer , Lundgren Dan , Sennerby Lars , Lundgren Anna Karin
Published: September 2003

Abstract: The aims of the present investigation were to study (1) the influence of preimplant (4 weeks) surgical intervention and (2) the influence of the implant placement per se on bone density and mineralized bone–implant contact (BIC) at implant sites in the rabbit jawbone. The experiment was performed in the edentulous area of the maxillas of 16 adult rabbits. In eight rabbits, the alveolar bone on the left side (test) was surgically exposed and a groove was prepared in the bone crest. Trabecular bone and marrow tissue were removed, and a bioabsorbable barrier membrane was placed to cover the groove. The right side underwent no treatment and served as the control. Four weeks later, a screw‐shaped titanium implant was placed transversally through the maxilla, penetrating both the test and the control areas. After another 4 weeks of healing, the animals were killed to obtain ground sections for histomorphometry. Untreated jaws from eight rabbits served as reference specimens. In the rabbits subjected to surgery, the areas (mm2) of both mineralized bone and marrow tissue were similar for test and control (4.9 ± 1.7 vs. 5.1 ± 2.2 and 6.3 ± 5.7 vs. 6.8 ± 5.7 for bone and marrow, respectively). The BIC (%) for all threads was significantly lower on the test side than on the control side (32.1 ± 27.7 vs. 47.7 ± 20.3). The bone density (%) of the total experimental area was similar for test and control (48.5 ± 12.1 vs. 46.5 ± 9.3), as was the bone density in the area within the implant thread valleys and their mirror areas (43.0 ± 13.9 vs. 41.3 ± 13.5, and 40.2 ± 11.0 vs. 40.3 ± 7.2 for thread area and mirror area, respectively). The bone density of the total experimental area in the untreated rabbits was 35.9 ± 5.2%. This value was significantly lower than the values in the total experimental areas (test and control) of the surgically treated rabbits. Similarly, the density of the reference area in the untreated rabbits was 25.4 ± 5.3%, which was also significantly lower than the bone density of the periimplant area of the surgically treated rabbits. We conclude that the surgical trauma caused by the placement of implants in the maxilla of rabbits significantly enhanced the bone density of the implant sites. Surgical intervention in the implant sites 4 weeks prior to the implant placements, however, did not further enhance bone density or BIC.
Effect of rhBMP‐2 on guided bone regeneration in humans
Authors: Jung Ronald E. , Glauser Roland , Schärer Peter , Hämmerle Christoph H. F. , Sailer Hermann F. , Weber Franz E.
Published: September 2003

Abstract: The aim of the present clinical study was to test whether or not the addition of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) to a xenogenic bone substitute mineral (Bio‐Oss®) will improve guided bone regeneration therapy regarding bone volume, density and maturation. In 11 partially edentulous patients, 34 Brånemark implants were placed at two different sites in the same jaw (five maxillae, six mandibles) requiring lateral ridge augmentation. The bone defects were randomly assigned to test and control treatments: the test and the control defects were both augmented with the xenogenic bone substitute and a resorbable collagen membrane (Bio‐Gide®). At the test sites, the xenogenic bone substitute mineral was coated with rhBMP‐2 in a lyophilization process. Following implant insertion (baseline), the peri‐implant bone defect height was measured from the implant shoulder to the first implant–bone contact. After an average healing period of 6 months (SD 0.17, range 5.7–6.2), the residual defects were again measured and trephine burs were used to take 22 bone biopsies from the augmented regions. The healing period was uneventful except for one implant site that showed a wound dehiscence, which spontaneously closed after 4 weeks. Later at reentry, all implants were stable. At baseline, the mean defect height was 7.0 mm (SD 2.67, range 3–12 mm) at test and 5.8 mm (SD 1.81, range 3–8 mm) at control sites. At reentry, the mean defect height decreased to 0.2 mm (SD 0.35, range 0–1 mm) at test sites (corresponding to 96% vertical defect fill) and to 0.4 mm (SD 0.66, range 0–2 mm) at the control site (vertical defect fill of 91%). Reduction in defect height from baseline to reentry for both test and control sites was statistically significant (Wilcoxon P<0.01). Histomorphometric analysis showed an average area density of 37% (SD 11.2, range 23–51%) newly formed bone at test sites and 30% (SD 8.9, range 18–43%) at control sites. The fraction of mineralized bone identified as mature lamellar bone amounted to 76% (SD 14.4, range 47.8–94%) at test compared to 56% (SD 18.3, range 31.6–91.4%) at control sites (paired t‐test P<0.05). At BMP‐treated sites 57% (SD 16.2, range 29–81%) and at control sites 30% (SD 22.6, range 0–66%) of the surface of the bone substitute particles were in direct contact with newly formed bone (paired t‐test P<0.05). It is concluded that the combination of the xenogenic bone substitute mineral with rhBMP‐2 can enhance the maturation process of bone regeneration and can increase the graft to bone contact in humans. rhBMP‐2 has the potential to predictably improve and accelerate guided bone regeneration therapy.
Correlation of insertion torques with bone mineral density from dental quantitative CT in the mandible
Authors: Beer Andreas , Gahleitner André , Holm Anders , Tschabitscher Manfred , Homolka Peter
Published: September 2003

Abstract: Objective: The aim of this study was to establish a correlation between bone mineral density measured preoperatively with dental computed tomography (CT), and insertion torque of screw‐shaped dental implants.

Material and methods: In eight human mandibles obtained postmortem, bone mineral density (BMD) was measured with dental quantitative CT (DQCT) and correlated with insertion torque values at 45 implant sites during insertion of screw‐shaped dental implants (Brånemark System MKIII, Nobel Biocare, AB, Göteborg, Sweden).

Results: A significant correlation (r=0.86, P<0.001) between BMD and torque values was observed, indicating that local BMD at a specific implant position is related to the supportive capacity of the jawbone. BMD exhibited no correlation with bone height or position.

Conclusion: The noninvasive assessment of BMD using a DQCT scan employing a low‐dose protocol may be used to estimate expected primary stability depending on BMD, implant type and preparation procedure. These data may therefore help the surgeon to select the optimum implant position, implant type and operation technique.
Implant stability and histomorphometry: a correlation study in human cadavers using stepped cylinder implants
Authors: Nkenke Emeka , Hahn Michael , Weinzierl Konstanze , Radespiel‐Tröger Martin , Neukam Friedrich Wilhelm , Engelke Klaus
Published: September 2003

The aim of the present study was to determine the correlation between the primary stability of dental implants placed in edentulous maxillae and mandibles, the bone mineral density and different histomorphometric parameters. After assessing the bone mineral density of the implant sites by computed tomography, 48 stepped cylinder screw implants were installed in four unfixed human maxillae and mandibles of recently deceased people who had bequeathed their bodies to the Anatomic Institute I of the University of Erlangen‐Nuremberg for medical–scientific research. Peak insertion torque, Periotest values and resonance frequency analysis were assessed. Subsequently, histologic specimens were prepared, and bone‐to‐implant contact, the trabecular bone pattern factor (TBPf), the density of trabecular bone (BV/TV) and the height of the cortical passage of the implants were determined. The correlation between the different parameters was calculated statistically. The mean resonance frequency analysis values (maxilla 6130.4±363.2 Hz, mandible 6424.5±236.2 Hz) did not correlate with the Periotest measurements (maxilla 13.1±7.2, mandible –7.9±2.1) and peak insertion torque values (maxilla 23.8±2.2 N cm, mandible 45.0±7.9 N cm) (P=0.280 and 0.193, respectively). Again, no correlations could be found between the resonance frequency analysis, the bone mineral density (maxilla 259.2±124.8 mg/cm3, mandible 349.8±113.3 mg/cm3), BV/TV (maxilla 19.7±8.8%, mandible 34.3±6.0%) and the TBPf (maxilla 2.39±1.46 mm−1, mandible –0.84±3.27 mm−1) (P=0.140 and 0.602, respectively). However, the resonance frequency analysis values did correlate with bone‐to‐implant contact of the oral aspect of the specimens (maxilla 12.6±6.0%, mandible 35.1±5.1%) and with the height of the crestal cortical bone penetrated by the implants in the oral aspect of the implant sites (maxilla 2.1±0.7 mm, mandible 5.1±3.7 mm) (P=0.024 and 0.002, respectively). The Periotest values showed a correlation with the height of the crestal cortical bone penetrated by the implants in the buccal aspect of the implant sites (maxilla 2.5±1.2 mm, mandible 5.4±1.2 mm) (P=0.015). The resonance frequency analysis revealed more correlations to the histomorphometric parameters than the Periotest measurements. However, it seems that the noninvasive determination of implant stability has to be improved in order to give a more comprehensive prediction of the bone characteristics of the implant site.
Ceramic hydroxyapatite coating on titanium implants drives selective bone marrow stromal cell adhesion
Authors: Torensma Ruurd , Ter Brugge Petra J. , Jansen John A. , Figdor Carl G.
Published: September 2003

Abstract:
The aim of this study was to determine the cell characteristics that regulate implant osseointegration. The heterogeneity of bone marrow stromal cells obtained from 11 donors was assessed by measuring the expression of a large panel of adhesion molecules. Large differences in expression of adhesion molecules were detected depending on the culture conditions used. Cells cultured in fetal bovine serum induced the expression of different adhesion molecules from cells cultured in human serum. Donor‐to‐donor variation was determined by measuring the expression of adhesion molecules for stromal cells obtained from different donors that were processed identically. Fat adherent cells but also loose bone marrow cells showed large differences in expression of some but not all adhesion molecules. The flow cytometric data demonstrated large heterogeneity in expression of adhesion molecules, and this heterogeneity was influenced by culture conditions and varied from donor to donor. This demonstrates that the implant encounters different cell types, which could lead to different levels of integration. Surprisingly, in vitro only a subfraction of bone marrow stromal cells attached to titanium coated with ceramic hydroxyapatite. Adaptation of all cell types present in heterogeneous bone marrow to a coated surface is apparently not possible. Differential binding was not caused by aberrant staining of the stromal cells as the results were confirmed with bone marrow cells obtained from transgenic GFP mice. These results demonstrate that hydroxyapatite ceramics are selective in cell recruitment from the bone marrow, explaining the differences found in vivo for these coatings compared with titanium.
Critical review of immediate implant loading
Authors: Gapski Ricardo , Wang Hom‐Lay , Mascarenhas Paulo , Lang Niklaus P.
Published: September 2003

Background: Implant dentistry has become successful with the discovery of the biological properties of titanium. In the original protocol, studies have advocated a 2‐stage surgical protocol for load‐free and submerged healing to ensure predictable osseointegration. However, the discomfort, inconvenience, and anxiety associated with waiting period remains a challenge to both patients and clinicians. Hence, loading implant right after placement was attempted and has gained popularity among clinicians. Issues/questions related to this approach remain unanswered. Therefore, it is the purpose of this review article to (1) review and analyze critically the current available literature in the field of immediate implant loading and (2) discuss, based on scientific evidence, factors that may influence this treatment modality.

Material and Methods: Literature published over the past 20 years was selected and reviewed. Findings from these studies were discussed and summarized in the tables. The advantages and disadvantages associated with immediate implant loading were analyzed. Factors that may influence the success of immediate implant loading, including patient selection, type of bone quality, required implant length, micro‐ and macrostructure of the implant, surgical skill, need for achieving primary stability/control of occlusal force, and prosthesis guidelines, were thoroughly reviewed and discussed.

Results and Conclusion: Various studies have demonstrated the feasibility and predictability of this technique. However, most of these articles are based on retrospective data or uncontrolled cases. Randomized, prospective, parallel‐armed longitudinal human trials are primarily based on short‐term results and long‐term follow‐ups are still scarce in this field. Nonetheless, from available literature, it may be concluded that anatomic locations, implant designs, and restricted prosthetic guidelines are key to ensure successful outcomes. Future studies, preferably randomized, prospective longitudinal studies, are certainly needed before this approach can be widely used.
Ridge preservation following tooth extraction using a polylactide and polyglycolide sponge as space filler: a clinical and histological study in humans
Authors: Serino Giovanni , Biancu Salvatore , Iezzi Giovanna , Piattelli Adriano
Published: September 2003

Abstract: Background: The placement of different graft materials and/or the use of occlusive membranes to cover the extraction socket entrance are techniques aimed at preserving/reducing alveolar ridge resorption. The use of grafting materials in fresh extraction sockets has, however, been questioned because particles of the grafted material have been found in alveolar sockets 6–9 months following their insertion.

Aim: The aims of the study were to (i) evaluate whether alveolar ridge resorption following tooth extraction could be prevented or reduced by the application of a bioabsorbable polylactide–polyglycolide sponge used as a space filler, compared to natural healing by clot formation, and (ii) evaluate histologically the amount and quality of bone tissue formed in the sockets, 6 months after the use of the bioabsorbable material.

Material and methods: Thirty‐six patients, undergoing periodontal therapy, participated in this study. All patients were scheduled for extraction of one or more compromised teeth. Following elevation of full‐thickness flaps and extraction of teeth, measurements were taken to evaluate the distance between three landmarks (mesio‐buccal, mid‐buccal, disto‐buccal) on individually prefabricated stents, and the alveolar crest. Twenty‐six alveolar sockets (test) were filled with a bioabsorbable polylactide–polyglycolide acid sponge (Fisiograft®), while 13 sockets (controls) were allowed to heal without any filling material. The flaps were sutured with no attempt to achieve primary closure of the surgical wound. Re‐entry for implant surgery was performed 6 months following the extractions. Thirteen biopsies (10 test and three control sites) were harvested from the sites scheduled for implant placement.

Results: The clinical measurements at 6 months revealed, in the mesial‐buccal site, a loss of bone height of 0.2 mm (1.4 SD) in the test and 0.6 mm (1.1 SD) in the controls; in the mid‐buccal portion a gain of 1.3 mm (1.9 SD) in the test and a loss of 0.8 mm (1.6 SD) in the controls; and in the distal portion a loss of 0.1 mm (1.1 SD) in the test and of 0.8 (1.5 SD) mm in the controls. The biopsies harvested from the test sites revealed that the new bone formed at 6 months was mineralized, mature and well structured. Particles of the grafted material could not be identified in any of the 10 test biopsies. The bone formed in the control sites was also mature and well structured.

Conclusion: The results of this study indicate that alveolar bone resorption following tooth extraction may be prevented or reduced by the use of a bioabsorbable synthetic sponge of polylactide–polyglycolide acid. The quality of bone formed seemed to be optimal for dental implant insertion.
A bioactive bone cement containing Bis‐GMA resin and A–W glass‐ceramic as an augmentation graft material on mandibular bone
Authors: Fujimura Kazuma , Bessho Kazuhisa , Okubo Yasunori , Segami Natsuki , Iizuka Tadahiko
Published: September 2003

Abstract: The potential of a bioactive bone cement (BABC) as an onlay graft material for the mandible with and without the periosteum was investigated in rabbits. Its matrix consists of bisphenol‐α‐glycidyl methacrylate (Bis‐GMA) and triethylene‐glycol dimetacrylate (TEGDMA) and its filler is silane‐treated CaO–SiO2–P2O5–MgO–CaF2 glass (A–W glass‐ceramic) powder. The BABC was pasted onto the mandible under the periosteum in Group 1, and onto the mandible with the periosteum removed in Group 2 and allowed to set in situ. In both groups, the cement–bone interface was filled by new bone at 4, 12 and 48 weeks, and bone grew from adjacent bone tissue into the cement–soft tissue interface at 12 and 48 weeks. There were no differences in the rate of bone formation between the groups. The shearing strength increased progressively from 0.25±0.10 MPa (mean±SD) at week 1 to 7.98±0.62 MPa at week 48. The results suggest that the BABC has good handling properties, a high bonding strength and good biocompatibility, and that it has potential for clinical application as a substitute material for autogenous bone transplantation.
The anchorage of Brånemark and ITI implants of different lengths. I. An experimental study in the canine mandible
Authors: Bernard Jean‐Pierre , Szmukler‐Moncler Serge , Pessotto Stéphane , Vazquez Lydia , Belser Urs C.
Published: September 2003

Abstract: The anchorage of machined Brånemark and ITI TPS‐coated implants of various lengths was investigated in an animal model. Brånemark fixtures 7 and 10 mm long and ITI implants 6 and 10 mm long were inserted in the mandible of dogs and were reverse‐torqued after 3 months of healing. The failing mode was different for the two implant systems. For the ITI implants, loosening coincided with the peak reverse‐torque values. For the Brånemark fixtures, two reverse‐torque values were identified and recorded, a ‘start to rotate’ and a peak value. The ‘start to rotate’ values for the 7 and 10 mm Brånemark fixtures were 36.67 and 38.57 Ncm, respectively, the peak values were 61.88 and 69.13 Ncm. The increase in implant length from 7 to 10 mm did not significantly improve the anchorage. The mean reverse‐torque values for the 6‐ and 10‐mm ITI implants were 104.66 and 192.25 Ncm, respectively; the difference was statistically significant. The mean removal torque of the 6‐mm ITI implant was higher than the 7‐ and 10‐mm Brånemark implants. It is suggested that the distinct anchorage magnitude and the distinct loosening patterns registered for both implant systems might be related to the various surface states. The latter might account for the different failure tendencies mentioned in the literature for short Brånemark and ITI implants.
Ratio of immature cornified envelopes does not correlate with parakeratosis in inflammatory skin disorders
Authors: Hirao Tetsuji , Terui Tadashi , Takeuchi Izuho , Kobayashi Hiromi , Okada Mikiko , Takahashi Motoji , Tagami Hachiro
Published: September 2003

Abstract:  We have previously established a non‐invasive method to evaluate the maturity of cornified envelopes (CEs), and have reported the appearance of immature CEs in the stratum corneum (SC) with poor barrier function, such as the SC of the face. The purpose of the present study was to evaluate CEs in inflammatory skin disorders, and to clarify the relationship between the appearance of the immature CEs and parakeratosis, which is often used as a marker for defective keratinization in inflammatory skin disorders.

Cornified envelopes in the outermost SC of involved areas of psoriasis vulgaris (PV) and atopic dermatitis (AD) were strikingly heterogeneous, and consisted of immature CEs stained with anti‐involucrin and mature CEs stained with Nile red, whereas CEs of the uninvolved areas were relatively homogeneous, exhibiting mature phenotype. The ratio of immature CEs was significantly higher in the involved areas of PV and AD than that in the corresponding uninvolved areas, suggesting that defective CE maturation may, at least in part, account for the inflammatory disorders.

Simultaneous evaluation of CE maturity and parakeratosis was carried out by a combination of involucrin immunostaining and nuclear staining of detergent‐dissociated corneocytes. In the involved area of PV, four types of corneocytes in regard to the combination of involucrin staining and nuclear remnant were observed, while both immature CEs and parakeratosis were more often detected in the involved areas of PV than in the uninvolved areas or the upper arm of healthy subjects as a normal control. Thus, corneocytes with involucrin‐positive immature CEs were not always associated with parakeratosis at the cellular level. In the involved areas of PV, the ratio of immature CEs and that of parakeratosis were heterogeneous, depending on the cases, and no correlation between the ratios was observed. Inter‐individual and intraindividual variations in CE maturity were also suggested by the heterogeneous localization of involucrin in the psoriatic epidermis as examined by immunohistochemistry. In addition, in the face of healthy subjects, four types of corneocytes were similarly detected, and the ratio of immature CEs was significantly higher than that of parakeratosis. These results obviously suggest that the maturation of CEs and disappearance of nuclei are differentially regulated in the epidermis.
Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin test
Authors: Caproni M. , Volpi W. , Macchia D. , Giomi B. , Manfredi M. , Campi P. , Cardinali C. , D'Agata A. , Fabbri P.
Published: September 2003

Abstract:  In approximately one‐third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high‐affinity IgE receptor and/or against IgE can be detected and a wheal‐and‐flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum‐evoked histamine‐release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL‐4, IL‐5, IFN‐γ), chemokines and chemokine receptors (IL‐8, CCR3, CXCR3), and adhesion molecules (ICAM‐1, VCAM‐1, ELAM‐1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22–57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control.

In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL‐4 and IL‐5 could only be observed in lesional skin, while IFN‐γ showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL‐8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system.
Human epidermal energy metabolism is functionally anaerobic
Authors: Ronquist Gunnar , Andersson Anders , Bendsoe Niels , Falck Bengt
Published: September 2003

Abstract:  We have reported that epidermal Langerhans cells possess an H+‐extruding mechanism signalling their existence in an anaerobic environment. This study highlights the energy metabolism of human epidermis. In their habitual state the keratinocytes contain more lactate than do most other cell types. Their lactate production in vitro is vigorous and independent of oxygen and most of it is released to the medium. Autoincubation of the epidermis under starved conditions resulted in a 30% increase of lactate, indicating ongoing glycogenolysis. Iodoacetate inhibited lactate production by > 90%. Energy charge values were low, approximately 0.82, and comparable with those previously reported for smooth muscle. Moreover, the overwhelming majority of the keratinocytic mitochondria had an appearance markedly deviating from those in the Langerhans cells, melanocytes and fibroblasts, and, above all, were characterized by an enormous reduction of the inner membrane. This structure is in all probability incompatible with an effective oxidative metabolism of glucose. We conclude that epidermal energy metabolism is predominantly anaerobic in spite of the formal presence of mitochondria. The high production of lactate obviously demands extracellular transport pathways for rapid elimination of this organic acid. An extracellular space complying with such a demand emerges on electron microscopy when an isotonic glutaraldehyde‐based fixative is used. The prevailing view regarding the size of the extracellular space is based on the common use of hypotonic fixatives, such as Karnovski's fixative, which causes gross cellular swelling and concomitant near total elimination of the extracellular space, leaving interstices with a diameter significantly smaller than that allowing fluid flow.
New mechanism for amino acid influx into human epidermal Langerhans cells: L‐dopa/proton counter‐transport system
Authors: Falck Bengt , Bendsoe Niels , Ronquist Gunnar
Published: September 2003

Abstract:  We have characterized a stereospecific transport mechanism for L‐dopa into human epidermal Langerhans cells (LCs). It is different from any other amino acid transport system. It is highly concentrative, largely pH‐independent, and independent of exogenous Na+, glucose and oxygen, and fuelled by a renewable intracellular energy source inhibited by iodoacetate but not by arsenate. We propose that the mechanism is a unidirectional L‐dopa/proton counter‐transport system. We have recently demonstrated anaerobic glycolysis in human epidermis, which substantiates the need of proton pumps for resident LCs. The findings prompt a re‐evaluation of the profound changes LCs undergo when exposed to oxygen in aerobic culture. L‐dopa is not metabolized by LCs but can rapidly be dislocated to the intercellular space by certain extracellular amino acids, i.e. LCs can profit by L‐dopa in a dualistic way, altogether a remarkable biological phenomenon.
Disruption of the suprabasal keratin network by mutation M150T in the helix initiation motif of keratin 10 does not affect cornified cell envelope formation in human epidermis
Authors: Akiyama M. , Takizawa Y. , Sawamura D. , Matsuo I. , Shimizu H.
Published: September 2003

Abstract:  Keratin 10 (K10) is known to be tightly bound to the cornified cell envelope (CCE) and this binding is thought to play an important role in enhancing the structural integrity of the cornified cells. Bullous congenital ichthyosiform erythroderma (BCIE) is a genetic disorder of keratinization caused by gene mutations in the conserved sequences of keratin 1 (K1) or K10, which leads to abnormal suprabasal keratin network assembly. In BCIE patients' skin, the keratin network abnormalities make the upper spinous and granular keratinocytes fragile and result in blister formation. However, the exact pathomechanism of the hyperkeratosis seen in BCIE is still unknown. The involvement of the CCE in the pathomechanism of hyperkeratosis in BCIE is controversial. Abnormal CCE assembly may cause hyperkeratosis as reported in cases of lamellar ichthyosis. Binding of K10 to CCE is thought to be a vital connection between the suprabasal keratin filament network and CCE. We hypothesize that abnormal suprabasal keratin assembly caused by either K1 or K10 mutations can disrupt CCE formation, resulting in the hyperkeratosis observed in BCIE. To clarify whether K10 and keratin network defects affect CCE formation in vivo, the ultrastructural and immunohistological features of CCE were studied in the epidermis of two Japanese BCIE patients from two independent families carrying an identical missense mutation M150T in the helix initiation motif of K10. Ultrastructurally, a 15‐nm‐thick, dense, normal‐appearing CCE was formed at the cell periphery of the keratinized epidermal cells. Light and electron microscopic immunolabeling revealed that the major CCE precursor proteins, involucrin and loricrin, were normally distributed and restricted to CCE of the epidermis. Immunofluorescent labeling showed that epidermal TGases, TGase 1, TGase 2 and TGase 3, were expressed normally in the epidermis. These findings suggest that a normal CCE is formed during the process of human epidermal keratinization, even if the suprabasal keratin filament network is disrupted as with this particular K10 mutation, M150T in BCIE.
Long‐term growth arrest of PUVA‐treated fibroblasts in G2/M in the absence of p16INK4a, p21CIP1 or p53
Authors: Ma W. , Hommel C. , Brenneisen P. , Peters T. , Smit N. , Sedivy J. , Scharffetter‐Kochanek K. , Wlaschek M.
Published: September 2003

Abstract:  Premature aging of the skin is a prominent side‐effect of psoralen photoactivation, a therapy used for different skin disorders. Recently, we demonstrated that treatment of fibroblasts with 8‐methoxypsoralen and ultraviolet A irradiation resulted in growth arrest with morphological and functional changes reminiscent of replicative senescence. To further elucidate the underlying molecular mechanisms, we analysed the cell‐cycle phases of the growth‐arrested fibroblasts. After PUVA treatment, fibroblasts arrested in G2/M, in contrast to spontaneously senesced fibroblasts arresting in a cell‐cycle phase with many features similar to G1. To address the role of the cell‐cycle controlling genes p16INK4a, p21CIP1 and p53, we analysed the expression of these genes. p16INK4a, p21CIP1 and p53 protein levels increased substantially with different time kinetics in growth‐arrested fibroblasts. Because p16INK4a, p21CIP1 and p53 are involved in replicative senescence, we applied the PUVA regimen to fibroblasts deficient in either of these genes. p16INK4a, p21CIP1 and p53 null mutant fibroblast strains underwent growth arrest with a senescent phenotype similar to wild‐type human fibroblasts. Based on these results, we propose that redundant or alternate pathways are involved in the response of dermal fibroblasts to PUVA treatment resulting in a phenocopy of replicative senescence in vitro.
Topical minoxidil counteracts stress‐induced hair growth inhibition in mice
Authors: Arck Petra Clara , Handjiski Bori , Peters Eva M. J. , Hagen Evelin , Klapp Burghard F. , Paus Ralf
Published: September 2003

Abstract:  Stress has long been suspected as a possible cause of hair loss in various species, even though convincing experimental evidence has not been available. Recently, we have shown in a murine model that sonic stress alters hair growth and cycling in vivo, and have postulated the existence of a ‘brain‐hair follicle axis’ (BHA). In order to study whether a clinically available and widely used topically active hair growth stimulator mitigates stress‐triggered hair growth inhibition in this stress model, we have applied a 5% minoxidil solution. Female CBA/J mice were depilated and randomized in to two groups: control (n = 20) and sonic stress (n = 20). These groups were further divided and either treated daily with 5% minoxidil solution or vehicle alone. The stress group was exposed to sonic stress for 24 h starting 14 days after anagen induction by depilation. All mice were sacrificed 16 days after the depilation and assessed by quantitative histomorphometry. Sonic stress significantly increased the number of hair follicles with apoptotic cells and inhibited intrafollicular keratinocyte proliferation. In addition, the number of clusters of perifollicular MHC class II+ cells and degranulated perifollicular mast cells was significantly enhanced in the stressed mice. In accordance with previous findings, all stressed mice showed an advanced hair cycle progression towards catagen. All of these stress‐induced hair growth inhibitory changes along the BHA were down‐regulated by topical minoxidil application. This encourages one to explore clinically whether topical minoxidil is a safe and effective pharmacologic tool for the management of stress‐associated telogen effluvium in humans.
Age‐dependent generation of reactive oxygen species in the skin of live hairless rats exposed to UVA light
Authors: Yasui H. , Sakurai H.
Published: September 2003

Abstract:  Aging proceeds by highly complicated biochemical processes, in which the involvement of the reactive oxygen species (ROS) and free radicals has been implicated. Although the relationship between UV‐induced photoaging and ROS generation has been proposed, it has been difficult to establish direct proof of the generation of ROS in the skin under UV exposure. Recently, we reported finding endogenously generated ROS in the skin of live mice after UVA light exposure by a method of in vivo chemiluminescent detection, in which superoxide anion radical (·O2–) and singlet oxygen species (1O2) are contributed. In light of the results, we tried to understand the age‐dependent changes in ROS generation in the skin of hairless rats under UVA exposure. Chemiluminescent levels due to ROS in the untreated and UVA‐exposed skin decreased age dependently, and the signal intensities in old rats were significantly lower than those in young rats. However, the ratios of chemiluminescent intensities in the UVA‐exposed skin to those in the untreated skin were significantly enhanced in an age‐dependent manner. These results suggest that the antioxidative ability against ROS generation in the skin, possessed by antioxidant enzymes and low molecular weight antioxidants, is lowered age dependently.
Internalization via plasmalemmal vesicles: a route for antidesmoplakin autoantibodies into cultured human keratinocytes
Authors: Cauza Karla , Hinterhuber Gabriele , Mann Ulrike , Horvat Reinhard , Rappersberger Klemens , Wolff Klaus , Foedinger Dagmar
Published: September 2003

Abstract:  Recently, autoantibodies to desmoplakin I and II have been identified in a subset of patients with a severe form of erythema multiforme. These autoantibodies recognize a specific peptide sequence at the carboxy terminal domain of desmoplakin I and II responsible for interaction with keratin filaments. Desmoplakins are major constitutive proteins of the inner dense desmosomal plaque of keratinocytes and are entirely localized within the cells. With the assumption of pathogenecity for circulating autoantibodies, the question arose how antidesmoplakin autoantibodies enter keratinocytes. Utilizing immunhistochemical procedures for cell motility and time kinetic studies at the light‐ and electron‐microscopic level, we found that autoantibodies are bound at the cell surface of cultured human keratinocytes, internalized via plasmalemmal vesicles, and are found consecutively within tubulo‐vesicular structures inside the cells. At the same time, a fraction of antibodies can be detected at the inner dense desmosomal plaques. Immunogold labeling reveals internalization of autoantibodies in small non‐coated plasmalemmal vesicles positive for caveolin. These observations indicate that vesicular transport may represent a relevant biological mechanism for antidesmoplakin autoantibodies to enter keratinocytes and allow access to their corresponding antigenic target in vivo.
Carbohydrate expression and modification during keratinocyte differentiation in normal human and reconstructed epidermis
Authors: Méhul Bruno , Corre Christophe , Capon Catherine , Bernard Dominique , Schmidt Rainer
Published: September 2003

Abstract:  Using fluorescein isothiocyanate (FITC)‐labeled lectins we were able to demonstrate the presence of specific carbohydrate moieties in normal human and reconstructed epidermis. Evidence is provided that in both cases the strongly reduced lectin staining at the level of the stratum corneum is the result of a hindered accessibility of the lectins in this lipid‐rich hydrophobic environment. Isolated corneocytes and purified cornified envelopes (CEs) exhibited clearly glycosylated structures reacting with distinct lectins. The presence of glycosidase activity, particularly in the upper layers of the epidermis characterized by an acidic environment (pH 5.5), indicates that modifications of the sugar residues might be important in epidermal homeostasis, barrier behavior and desquamation. Absent or strongly reduced glycosidase activity in the stratum corneum of reconstructed epidermis with an impaired pH gradient could be in part responsible for the reduced barrier function and the lack of desquamation in this model.