bluuebunny/crossref_metadata_2025 huggingface dataset:
Computer‐aided placement of endosseous oral implants in patients after ablative tumour surgery: assessment of accuracy
Authors: Wagner Arne , Wanschitz Felix , Birkfellner Wolfgang , Zauza Konstantin , Klug Clemens , Schicho Kurt , Kainberger Franz , Czerny Christian , Bergmann Helmar , Ewers Rolf
Published: May 2003

Abstract: The objective of this study was to evaluate the feasibility and accuracy of a novel surgical computer‐aided navigation system for the placement of endosseous implants in patients after ablative tumour surgery. Pre‐operative planning was performed by developing a prosthetic concept and modifying the implant position according to surgical requirements after high‐resolution computed tomography (HRCT) scans with VISIT, a surgical planning and navigation software developed at the Vienna General Hospital. The pre‐operative plan was transferred to the patients intraoperatively using surgical navigation software and optical tracking technology. The patients were HRCT‐scanned again to compare the position of the implants with the pre‐operative plan on reformatted CT‐slices after matching of the pre‐ and post‐operative data sets using the mutual information‐technique. A total of 32 implants was evaluated. The mean deviation was 1.1 mm (range: 0–3.5 mm). The mean angular deviation of the implants was 6.4° (range: 0.4°– 17.4°, variance: 13.3°). The results demonstrate, that adequate accuracy in placing endosseous oral implants can be delivered to patients with most difficult implantologic situations.
Implant‐supported fixed cantilever prostheses in partially edentulous arches. A seven‐year prospective study
Authors: Romeo Eugenio , Lops Diego , Margutti Emilio , Ghisolfi Marco , Chiapasco Matteo , Vogel Giorgio
Published: May 2003

Abstract: The purpose of the following study was to evaluate the medium‐ to long‐term prognosis of implant‐supported cantilever fixed prostheses, and to establish to what degree this is influenced by factors such as length, type of cantilever (mesial or distal), and opposite dentition versus cantilever prostheses. This study was performed on a sample of 38 partially edentulous patients treated between January 1994 and March 2001 with 49 partial cantilever fixed prostheses supported by 100 implants. Marginal bone resorption (MBL) has been studied and used as a reference parameter to define therapeutic success. The MBL measurement was made possible by transposing X‐ray images of patients selected on a PC and then using a software program. Statistical analysis was carried out for possible correlation between peri‐implant bone resorption and the parameters considered in this study: length and type (mesial or distal) of cantilever and opposite dentition to cantilever prostheses. Seven years after loading cantilever prostheses, the overall cumulative implant survival rate (OCSR) was 97%, and the prostheses success rate is 98%. Mesial cantilever prostheses registered a lower success rate (97.1%) than distal cantilever prostheses (100%). Furthermore, a better prognosis was not observed when the opposite dentition of the prostheses comprised natural teeth, or fixed prostheses on natural teeth, when compared with the cases in which opposite teeth were implant‐supported fixed prostheses. The authors concluded that medium‐term prognosis of implant‐supported cantilever fixed prostheses and traditional implant‐supported fixed prostheses was comparable. However, a thorough pre‐treatment analysis of risk factors regarding implant‐supported prosthesis survival is important.
Bone contact, growth, and density around immediately loaded implants in the mandible of mini pigs
Authors: Nkenke Emeka , Lehner Bernhard , Weinzierl Konstanze , Thams Ulf , Neugebauer Jörg , Steveling Helmut , Radespiel‐Tröger Martin , Neukam Friedrich Wilhelm
Published: May 2003

Abstract: The aim of the study was to compare the bone mineral apposition rate (BMAR) of immediately loaded implants with an unloaded control during the early healing phase in the partially edentulous mandible. In seven mini pigs, three premolars and the first molar were removed in the left mandible. Three months later, five implants were installed. Four implants received a fixed provisional restoration and were loaded immediately. The most anterior implant was used as unloaded control. Polychromatic fluorescence labelling was performed to assess the BMAR. After 4 months, the implants were retrieved together with the adjacent bone. Histological specimens were prepared and subjected to a fluorescence microscopic and histomorphometric analysis. Two provisional restorations were found partially lost at the end of the observation period. One implant that had lost the splinting fixation showed soft connective tissue healing. The BMAR did not differ statistically significantly between loaded and unloaded implants and within the single groups during the observation period (BMARloaded days 14−42=1.8±0.2 μm/d, BMARloaded days 42−70=1.8±0.1 μm/d, BMARloaded days 70−98=1.6±0.1 μm/d, pBMARloaded days 14–42/42–70/70–98=0.156, BMARunloaded days 14−42=1.7±0.1 μm/d, BMARunloaded days 42−70=1.8±0.2 μm/d, BMARunloaded days 70−98=1.6±0.4 μm/d, pBMARunloaded days 14–42/42–70/70–98=0.368, pBMARloaded/unloaded days 14–42=0.073, pBMARloaded/unloaded days 42–70=0.098, pBMARloaded/unloaded days 70–98=0.262). Four months after implant placement, the bone‐to‐implant contact was 77.8±17.3% for the loaded and 78.0±5.8% for the unloaded implants (P=0.753). Immediate loading does not affect the bone mineral apposition rate when compared with unloaded implants. Rigid splinting seems to be the crucial factor for implant success. Uncontrolled masticatory forces can cause failure after partial loss of the provisional restoration.
Enzymatic degradation of collagen‐guided tissue regeneration membranes by periodontal bacteria
Authors: Sela Michael N. , Kohavi David , Krausz Emanuela , Steinberg Doron , Rosen Graciela
Published: May 2003

Abstract: Bacterial infection in the vicinity of guided tissue regeneration barrier membranes was shown to have a negative effect on the clinical outcomes of this increasingly used technique. Several oral and specifically periodontal bacteria were shown to adhere to such membranes in vivo and in vitro with a higher affinity to membranes constructed from collagen. The present study examined the role of periodontal bacteria and their enzymes in the degradation of commercially used collagen membranes. Degradation of two collagen membranes [BiomendTM (Calcitek®, Colla‐Tec Inc., Plainsboro, NJ) and Bio‐GideTM (Geistlich Biomaterials, Wolhousen, Switzerland)] labeled by fluorescein isothiocyanate was examined by measuring soluble fluorescence. Porphyromonas gingivalis, Treponema denticola and Actinobacillus actinomycetemcomitans and their enzymes were evaluated. Collagenase from Clostridium hystolyticum was used as a positive control. While whole cells of P. gingivalis were able to degrade both types of membranes, T. denticola could degrade Bio‐Gide membranes only and A. actinomycetemcomitans whole cells could degrade none of the membranes. Fractionation of P. gingivalis cells revealed that cell membrane associated proteases were responsible for the degradation of the two collagen membranes. In T. denticola, the purified major phenylalanine protease was found to be responsible for the degradation of Bio‐Gide membranes. These results suggest that proteolytic bacterial enzymes may take part in the degradation of collagen barrier membranes used for guided tissue regeneration.
Effects of hydroxyapatite‐coated and commercially pure titanium oral implant surfaces on compound nerve action potentials
Authors: Çehreli Murat C. , Onur Mehmet A. , Şahin Saime
Published: May 2003

Abstract: The aim of this study was to investigate the effects of hydroxyapatite‐coated and commercially pure titanium oral implants on nerve conduction. Isolated rat sciatic nerves were placed between two suction electrodes in a bath containing a tyrode solution. The implants were brought into intimate contact with the nerves and evoked compound action potentials (cAPs) were recorded before and after contact with the implants. The commercially pure titanium implants did not cause any change in cAPs. A gradual reduction in cAPs was observed for hydroxyapatite‐coated implants. However, this reduction was < 50% after an application time of 120 min. Recovery of the cAPs in this group was recorded after approximately 60 min. We conclude that, although intimate contact with hydroxyapatite‐coated implants leads to a reduction in cAPs in nerves in vitro, neither this surface nor a commercially pure titanium surface leads to irreversible neurotoxic effects.
In‐patient comparison of immediately loaded and non‐loaded implants within 6 months
Authors: Lorenzoni Martin , Pertl Christof , Zhang Kehao , Wegscheider Walther A.
Published: May 2003

Abstract: According to the Brånemark protocol, a stress‐free healing period is one of the most emphasised requirements for implant integration. Recent studies have encouraged a progressive shortening of the healing period and immediate loading has been proposed for the edentulous mandible. This prospective study evaluated the clinical outcomes of 14 immediately loaded FRIALIT‐2® implants compared with 28 non‐loaded controls in an in‐patient study. The results were based on clinical stability and on changes of bone level from implant placement to abutment connection 6 months after insertion. In the course of our investigation, seven patients with edentulous mandibles have been treated with 43 implants following an immediate‐loading protocol. Six FRIALIT‐2® implants were placed in the interforaminal region located at positions 34, 33, 32, 42, 43, 44. Bone level in relation to implant margin was measured and recorded. In order to obtain an in‐patient comparison of immediately loaded and non‐loaded implants, the ones at 33 and 43 were chosen to be immediately loaded by a Dolder‐bar retained overdenture. The implants in position 32, 34, 42 and 44 were covered and left to heal. After a healing period of 6 months, second stage surgery was carried out. The clinical criteria to be checked at this point were survival, Periotest values and marginal bone level at the loaded and non‐loaded implants. The mean Periotest value was −2.7 for the loaded and −5.6 for the non‐loaded implants. The Mann–Whitney U‐test showed that the difference was highly significant (P < 0.001). The mean bone level changes at prosthetic delivery were 0.9 mm resorption for the loaded implants and 0.33 mm for non‐loaded implants. The difference was highly significant (P < 0.001). No implant failures were observed up to the prosthetic restoration 6 months post insertion. The results of this investigation allowed for direct comparison of implant survival and clinical results between immediately loaded implants and standard implants. Clinical bone changes at the 6‐month evaluation demonstrated significantly higher crestal resorption around loaded implants. This fact was confirmed by higher median Periotest values (−3 vs. −6) of immediately loaded implants. According to the outcome of this study, immediate loading of two interforaminal implants with a Dolder‐bar resulted in an intimate bone apposition comparable with implants with submerged healing. Nevertheless, the coronal bone level as well as clinical stability (PTV) were significantly lower in the case of the immediately loaded implants. Future studies will be necessary to evaluate marginal bone resorption, Periotest values and clinical success rates of mandibular immediately loaded implants in the long‐term.
Morphology and dimensions of the mandibular jaw bone in the interforaminal region in patients requiring implants in the distal areas
Authors: Quirynen Marc , Mraiwa Nuri , Van Steenberghe Daniel , Jacobs Reinhilde
Published: May 2003

Abstract: This study aimed to analyse variations in the mandibular interforaminal morphology in an attempt to identify potential risks or contraindications for surgery, especially implant installation, in this particular region. A total of 210 spiral computer tomography (CT) examinations of patients requiring endosseous implant installation in the lower jaw were re‐evaluated to explore anatomical variations in bone morphology (shape and contour), and to measure parameters concerning height, width and inclination of the bone in the symphyseal atrea. All measurements were performed on the cross‐sectional reformatted images mesial to the mental foramina. A lingual concavity (with a depth of 6 ± 2.6 mm) was observed in 2.4% of the jaws, with a remaining bone height in that area ranging from 4.2 to 11.9 mm. A clearly lingual tilted/inclined morphology was seen in 28.1% of jaws with a mean angle of 67.6 ± 6.5°, but a relatively constant width (> 8.8 mm). The remaining jaws (69.5%) showed a slight broadening in the caudal direction. The morphologic parameters were influenced neither by age nor by gender. In conclusion, mandibles with a lingual concavity or a severe slope of the lingual cortex might confer increased risks of lingual perforations during trepanation surgery or graft harvesting as well as fenestrations during implant installation. The detection frequency of such variations within the lower jaw seems to advocate a profound dissection of the lingual site and, in the case of some special treatment strategies, additional cross‐sectional radiography.
A conical implant–abutment interface at the level of the marginal bone improves the distribution of stresses in the supporting bone
Authors: Hansson Stig
Published: May 2003

Abstract: It has been hypothesized that marginal bone resorption may result from microdamage accumulation in the bone. In light of this, a dental implant should be designed such that the peak stresses arising in the bone are minimized. The load on an implant can be divided into its vertical and horizontal components. In earlier studies, it was found that the peak bone stresses resulting from vertical load components and those resulting from horizontal load components arise at the top of the marginal bone, and that they coincide spatially. These peak stresses added together produce a risk of stress‐induced bone resorption. Using axisymmetric finite element analysis it was found that, with a conical implant–abutment interface at the level of the marginal bone, in combination with retention elements at the implant neck, and with suitable values of implant wall thickness and modulus of elasticity, the peak bone stresses resulting from an axial load arose further down in the bone. This meant that they were spatially separated from the peak stresses resulting from horizontal loads. If the same implant–abutment interface was located 2 mm more coronally, these benefits disappeared. This also resulted in substantially increased peak bone stresses.
Solcoseryl, a tissue respiration stimulating agent, significantly enhances the effect of capacitively coupled electric field on the promotion of bone formation around dental implants
Authors: Ochi Morio , Wang Pao‐Li , Ohura Kiyoshi , Takashima Shigenori , Kagami Hiroyuki , Hirose Yukito , Kaku Tohru , Sakaguchi Kunihiko
Published: May 2003

Abstract: In the present study we examined the combined effect of application of a capacitively coupled electric field (CCEF) and the tissue respiration stimulating agent, Solcoseryl, on the promotion of bone formation around dental implants histologically and mechanically. After a dental implant was inserted into each femur of Japanese white rabbits, Solcoseryl (2 ml/kg) was administered intravenously in the ear vein and a CCEF was applied for 4 h per day for 14 days. The degree of bone formation on microscopic observation, bone contact ratio, bone surface area ratio, and the level of removal torque of the implant in the Solcoseryl‐ and CCEF‐treated group were significantly higher than the respective value in the control group, which had not been treated with Solcoseryl nor CCEF. Thus, the combination of CCEF stimulation and Solcoseryl effectively promoted the formation of new bone. It is suggested that the clinical use of a combination of CCEF stimulation and Solcoseryl for dental implants promotes osseointegration.
Maxillary sinus floor elevation surgery
Authors: Timmenga Nicolaas M. , Raghoebar Gerry M. , Van Weissenbruch Ranny , Vissink Arjan
Published: May 2003

Abstract: Although augmentation of the maxillary sinus floor with autogenous bone grafts has become a well established preimplantology procedure, its effect on the function of the maxillary sinus has not been the subject of prospective human studies. In this prospective study the effects of sinus floor augmentation on maxillary sinus performance were evaluated. Seventeen consecutive patients who were to undergo augmentation of the maxillary sinus floor with an iliac crest autogenous bone graft agreed to participate in this study. All patients were subject to (i) extensive anamnestic and clinical investigation on sinusitis, (ii) conventional radiography (Waters' projection) and (iii) unilateral endoscopic inspection of the maxillary sinus. This triad of evaluations was performed preoperatively, immediately preceding the augmentation procedure (the maxillary sinus to be inspected endoscopically was randomly selected), and at 3 (at insertion of the implants) and 9 months (at uncovering of implants) postaugmentation. None of the 17 patients showed clinical or radiological signs of actual sinus pathology preoperatively, though 5 patients had a history of an impeded sinus clearance. By contrast, unilateral endoscopic evaluation revealed pre‐existing subclinical mucosal pathology in two out of five patients with a history of sinus clearance impairment and in one out of the other 12 patients. At 3 months' postaugmentation, clinical and radiographical examination showed chronic maxillary sinusitis in one non‐compromised patient. Moreover, serial unilateral endoscopic evaluation revealed subclinical maxillary mucosal pathology in four other patients (two of whom had a history of an impeded sinus clearance), confirmed by Waters' projection in three of these four patients. At 9 months' postaugmentation, only subclinical maxillary mucosal pathology was detected endoscopically in two patients (one compromised, one non‐compromised patient), confirmed by Waters' projection in this last patient. Five implants were lost during the 9‐month observation period. As is obvious from this prospective evaluation, the effects of the augmentation procedure on maxillary sinus performance in patients without signs of maxillary sinusitis are of no clinical significance.
Ten‐year follow‐up in a maxillary sinus augmentation using anorganic bovine bone (Bio‐Oss). A case report with histomorphometric evaluation
Authors: Sartori Stefano , Silvestri M. , Forni F. , Icaro Cornaglia A. , Tesei P. , Cattaneo V.
Published: May 2003

Abstract: Several bone grafting materials have been used in sinus augmentation procedures. Bio‐Oss (deproteinized and sterilized bovine bone) has shown to have osteoconductive properties and no inflammatory or adverse responses have been published. In spite of these successful results, histologic data regarding bone augmentation using Bio‐Oss in humans is scarce. The purpose of this study was to analyse the amount of Bio‐Oss ossification in a case of maxillary sinus augmentation, recording and comparing histomorphometric data 8 months, 2 and 10 years after surgery. This long‐term histologic evaluation of retrieved specimens has been performed, comparing histomorfometric measures at different times. Eight months after surgery we observed in 20 different thin sections of the specimen a mean amount of bone tissue (including medullar spaces) of 29.8% (and 70.2% of Bio‐Oss) ± 2.6. At 2 years the bone tissue increased to 69.7% + 2.7 and 10 years after surgery it was 86.7% ± 2.8. The comparison of the means for each time has shown a highly significant increasing trend in bone formation associated with Bio‐oss resorption: at 8 months, 2 and 10 years.
Identification of organic eluates from four polymer‐based dental filling materials
Authors: Michelsen Vibeke Barman , Lygre Henning , Skålevik Rita , Tveit Anne Bjørg , Solheim Einar
Published: May 2003

Elution from polymer‐based dental filling materials may have a potential impact on the biocompatibility of the materials. Since information from the manufacturers about ingredients in the materials often is incomplete, analyses of eluates from the materials are necessary for a better knowledge about possible harmful compounds. The aim of this study was to identify organic eluates from polymerized samples of two composites, one compomer and one resin‐reinforced glass ionomer cement. Samples were immersed in ethanol or Ringer's solution. Organic leachables were analyzed by gas chromatography–mass spectrometry. Identification was confirmed with reference substances, if available. Among components detected were monomers, co‐monomers, initiators, stabilizers, decomposition products and contaminants. Thirty‐two substances were identified and 17 were confirmed with reference substances. From elution in Ringer's we identified 13 eluates from Tetric Ceram, 10 from Z250, 21 from Dyract and six from Fuji II LC; HEMA, HC and CQ were found in all samples. From elution in ethanol 12 eluates from Tetric Ceram, 18 eluates from Z250, 19 from Dyract and 10 from Fuji II LC were identified. The diversity of eluates from the four materials under study is demonstrated. Owing to variation between the materials, the biocompatibility including the allergenic potential may be different.
Interaction of triclosan with eukaryotic membrane lipids
Authors: Lygre Henning , Moe Grete , Skålevik Rita , Holmsen Holm
Published: May 2003

The possibility that triclosan and PVM/MA (polyvinylmethyl ether/maleic acid) copolymer, additives to dentrifrices, could interact with eukaryotic membrane lipids was studied by two methods: first, by determining the pressure/molecular area isotherms at 37°C of glycerophospholipid monolayers, using the Langmuir technique; and second, by phase‐transition parameters in liposomes of the same lipids, using differential scanning calorimetry (DSC). Triclosan interacted, in a concentration‐independent manner, with monolayers of saturated phosphatidylcholines (PC; i.e. markers of the outer membrane leaflet of eukaryotic cells). Triclosan and PVM/MA copolymer mixtures were shown to clearly interact in a concentration‐dependent manner with PC. Triclosan was found to interact with liposomes of saturated and unsaturated phosphatidylcholines and phosphatidylserines (PS; i.e. markers of the inner membrane leaflet of eukaryotic cells), and saturated ethanolamines (PE; i.e. markers of the inner membrane leaflet of eukaryotic cells), resulting in a decrease of the lipid melting temperature (Tm). PVM/MA copolymer changed the Tm of PS, PC, and PE in different manners. By adding PVM/MA or triclosan–PVM/MA copolymer mixtures to 1‐stearoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphoserine (SOPS) no lipid transitions were detected. A biphasic change of the PC transition temperature resulted when triclosan or triclosan PVM/MA copolymer mixtures were added, indicating domain formation and change of the lipid polymorphism.
Masseter thickness, endurance and exercise‐induced pain in subjects with different vertical craniofacial morphology
Authors: Farella Mauro , Bakke Merete , Michelotti Ambra , Rapuano Alessia , Martina Roberto
Published: May 2003

The aim of the study was to compare neuromuscular features of the masseter muscle in subjects with different vertical craniofacial morphology. Fifteen short‐faced (mandibular plane‐Frankfurt plane angle < 15°) and 15 normal‐ to long‐faced (mandibular plane–Frankfurt plane angle ≥ 23°) male students participated. The thickness of the masseter was assessed by ultrasonography. Onset and endurance of exercise pain were recorded during sustained biting at a level of 15% of maximum voluntary contraction and 30 µV electromyographic activity. Pain and fatigue was measured on visual analog scales before and after the biting, as well as before and after 10 min chewing. Statistical comparison showed that the masseter muscle was significantly thicker (+15%) in the short‐faced than the normal‐ to long‐faced subjects. The pain onset time and endurance time were also consistently shorter in short‐faced subjects, whereas the intensity of pain and fatigue did not differ significantly between the two groups. Multiple stepwise regression showed positive influence from the mandibular plane inclination and the masseter thickness on the pain onset time and endurance time. The present findings support the concept that subjects with different craniofacial morphology show neuromuscular differences.
Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of oligodontia
Authors: Mostowska Adrianna , Kobielak Agnieszka , Biedziak Barbara , Trzeciak Wieslaw H.
Published: May 2003

Tooth development is regulated through a series of reciprocal interactions between the dental epithelium and mesenchyme and requires protein products of a number of genes. It has been reported that selective tooth agenesis is associated with mutations in human MSX and PAX9 genes. Mutational analysis of the two genes was performed in 25 individuals with familial or sporadic form of permanent tooth agenesis. Single‐stranded conformational polymorphism analysis revealed no mutations in the entire coding sequence of the MSX1 gene. In PAX9, a novel, heterozygous G151A transition in the sequence encoding the paired domain of the PAX9 protein was detected in a patient with agenesis of third molars, second premolars and incisors, but not in her parents, the remaining patients or 162 individuals with normal dentition. This is the first de novo mutation described in PAX9. Our results support the view that mutations in PAX9 could constitute a causative factor of oligodontia. We hypothesize that the G151A transition in PAX9 might be responsible for the sporadic form of tooth agenesis in this patient.
Dentin caries activity status related to hardness and elasticity
Authors: Zheng Lei , Hilton Joan F. , Habelitz Stefan , Marshall Sally J. , Marshall Grayson W.
Published: May 2003

This research tested the hypothesis that active and arrested carious dentin lesions have distinct structural characteristics and differ in atomic force microscopy‐based nano‐mechanical properties of the identifiable zones found in hydrated coronal carious lesions. Eight carious molars were used in this study. After longitudinally bisecting all the samples through the centers of carious lesions, they were divided into two subgroups: moderately active caries and arrested caries. The samples were highly polished and stained by caries detector, which allowed identification of four zones: pink, light pink, transparent and apparently normal. The mechanical properties were studied wet using atomic force microscopy. The results show that both groups contained the same zones, regardless of activity status, and different zones have different mechanical properties. Generally, the more demineralized outer zones (pink, light pink) were larger and the mechanical properties of the zones were lower for moderately active caries. For arrested caries, the transparent zone occupied a larger portion of the lesion and the reduced elastic modulus was not significantly different from the underlying normal zone, although its hardness was lower than the apparently normal zone.
Effect of lipopolysaccharides on vascular endothelial growth factor expression in mouse pulp cells and macrophages
Authors: Botero Tatiana M. , Mantellini Maria G. , Song Wenying , Hanks Carl T. , Nör Jacques E.
Published: May 2003

Vascular endothelial growth factor (VEGF), a potent pro‐angiogenic factor, might regulate the neovascularization observed in the pulp of teeth with deep caries. The purpose of this in vitro study was to evaluate the effect of bacterial lipopolysaccharides (LPS) on VEGF expression in dental pulp cells. Mouse odontoblast‐like cells (MDPC‐23) or undifferentiated pulp cells (OD‐21) were exposed to 0–20 µg ml−1Escherichia coli LPS or 0–80 µg ml−1Prevotella intermedia LPS. As controls, mouse macrophages or gingival fibroblasts were exposed to LPS, since these cells are known to secrete VEGF. The VEGF expression was evaluated by reverse transcriptase polymerase chain reaction or enzyme‐linked immunosorbent assay. The baseline expression levels of VEGF protein were higher in MDPC‐23 and OD‐21 than in fibroblasts or macrophages. Vascular endothelial growth factor protein expression was upregulated in MDPC‐23 and macrophages exposed to E. coli LPS, but not in OD‐21 cells or fibroblasts. Higher concentrations of P. intermedia LPS were required to induce VEGF expression in MDPC‐23 cells. Treatment with LPS did not affect VEGF expression at the mRNA level in any of the cells evaluated. These results demonstrate that bacterial LPS upregulates VEGF expression in odontoblast‐like cells and macrophages, and suggest that the regulation of VEGF expression occurs primarily at a post‐transcriptional level.
Dentin sialoprotein isoforms: detection and characterization of a high molecular weight dentin sialoprotein
Authors: Qin Chunlin , Brunn Jan C. , Baba Otto , Wygant James N. , McIntyre Bradley W. , Butler William T.
Published: May 2003

Dentin sialoprotein (DSP) is a glycoprotein accounting for 5–8% of the dentin non‐collagenous proteins. The cDNA sequence predicts that rat DSP has 13 potential casein kinase phosphorylation sites and six potential N‐linked glycosylation sites. However, its total phosphorylation level, as well as the nature and locations of the carbohydrate moieties, are unknown. Our findings in the present study show that rat DSP has 6.2 phosphates per molecule and that the majority of carbohydrates are attached to the protein through N‐linked glycosylations. During our separation of dentin non‐collagenous proteins with ion‐exchange chromatography, we observed high molecular weight components eluting late in the salt gradient that were recognized by anti‐DSP antibodies. We have purified these high molecular weight components using a monoclonal anti‐DSP antibody affinity column. Data from amino acid analysis, phosphate level measurements and Edman degradation of tryptic peptides unequivocally proved that the very acidic, high molecular weight components are isoforms of DSP (designated HMW‐DSP). Deglycosylation analysis indicates that the slower migration rate of HMW‐DSP on SDS‐PAGE results from its higher level of carbohydrate modifications.
Polymer structure of a light‐cured resin composite in relation to distance from the surface
Authors: Asmussen Erik , Peutzfeldt Anne
Published: May 2003

The aim of the investigation was to study the polymer structure of a light‐cured resin composite in relation to the distance from the irradiated surface. Ten cylinders (4 × 8 mm) of composite were light‐cured in a mold at 580 mW cm−2 for 40 s. The cylinders were expressed from the mold and, after 1 wk of dry storage at 37°C, embedded in dental stone. Grinding parallel to the long axis of the cylinders on carborundum paper exposed the resin composite. The Wallace hardness in relation to distance from the irradiated surface was measured before and after 1 d of ethanol storage. Before ethanol storage and at distances from the surface of 0.5–3.5 mm, no difference in hardness was recorded. The ethanol storage gave rise to a softening of the resin composite. The softening recorded at 3.0–3.5 mm was significantly more pronounced than the softening taking place at 0.5–2.5 mm. This result was explained by a slower polymerization occurring at the greater distances from the irradiated surface, resulting in a polymer with reduced crosslink density.
Dualistic actions of cromakalim and new potent 2H‐1,4‐benzoxazine derivatives on the native skeletal muscle KATP channel
Authors: Tricarico Domenico , Barbieri Mariagrazia , Antonio Laghezza , Tortorella Paolo , Loiodice Fulvio , Camerino Diana Conte
Published: May 2003

New 2H‐1,4‐benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP‐sensitive K+ channels (KATP) of native rat skeletal muscle fibres by using the patch‐clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituents such as methyl (–CH3), ethyl (–C2H5) or propyl (–C3H7) groups, while maintaining pharmacophore groups critical for conferring agonist properties.

The effects of these molecules were compared with those of cromakalim in the presence or absence of internal ATP (10−4 M). In the presence of internal ATP, all the compounds increased the macropatch KATP currents. The order of potency of the molecules as agonists was −C3H7 (DE50=1.63 × 10−8 M) >−C2H5 (DE50=1.11 × 10−7 M)>–CH3 (DE50=2.81 × 10−7 M)>cromak‐slim (DE50= 1.42 × 10−5 M). Bell‐shaped dose–response curves were observed for these compounds and cromakalim indicating a downturn in response when a certain dose was exceeded.

In contrast, in the absence of internal ATP, all molecules including cromakalim inhibited the KATP currents. The order of increasing potency as antagonists was cromakalim (IC50=1.15 × 10−8 M)–CH3 (IC50=2.6 × 10−8 M)>–C2H5 (IC50=4.4 × 10−8 M)>–C3H7 (IC50=1.68 × 10−7 M) derivatives.

These results suggest that the newly synthesized molecules and cromakalim act on muscle KATP channel by binding on two receptor sites that have opposite actions. Alternatively, a more simple explanation is to consider the existence of a single site for potassium channel openers regulated by ATP which favours the transduction of the channel opening. The alkyl chains at position 2 of the 2H‐1,4‐benzoxazine nucleus is pivotal in determining the potency of benzoxazine derivatives as agonists or antagonists.

British Journal of Pharmacology (2003) 139, 255–262. doi:10.1038/sj.bjp.0705233
Conventional‐type protein kinase C contributes to phorbol ester‐induced inhibition of rat myometrial tension
Authors: Kim Bokyung , Kim Yoon‐Sun , Ahn Jiyun , Kim Junghwan , Cho SungIl , Won Kyung‐Jong , Ozaki Hiroshi , Karaki Hideaki , Lee Sang‐Mok
Published: May 2003

Phorbol ester decreases muscle tension in the rat myometrium, and the effect is more potent in late‐pregnant myometrium than in nonpregnant myometrium. In the present study, we have examined the contribution of protein kinase C (PKC) isoforms to the phorbol ester‐induced inhibition of tension in rat uterine smooth muscle.

Thymeleatoxin (THX), a selective activator of conventional‐type PKC (cPKC), and 12‐deoxyphorbol 13‐isobutyrate (DPB), an activator of pan PKC, inhibited the tension induced by high K+, and inhibitions were significantly increased in pregnant myometrium compared to nonpregnant myometrium. The inhibition by DPB and THX of high K+‐induced tension was significantly attenuated when PKC was downregulated by long‐term pretreatment with THX and inhibited by Go6976, a cPKC inhibitor.

Of the cPKCs, PKCα is predominantly expressed in the rat myometrium, as detected by Western blot analysis. The expression of PKCα gradually increases from the beginning of gestation, reaching a maximum at day 21 of pregnancy. Treatment with DPB induced PKCα to translocate from the cytosol to the membrane in the pregnant myometrium. PKCɛ and PKCζ, other dominant PKC isoforms in the rat myometrium, decrease during gestation, reaching a minimum in late pregnancy.

These results suggest that cPKC may be at least partly involved in the PKC‐mediated inhibition of muscle tension in the rat myometrium.

British Journal of Pharmacology (2003) 139, 408–414. doi:10.1038/sj.bjp.0705237
Low endotoxemia prevents the reduction of gastric blood flow induced by NSAIDs: role of nitric oxide
Authors: Calatayud Sara , Canet Amparo , Bello Regina , Hernández Carlos , Martí Miguel , Barrachina M Dolores
Published: May 2003

The role of nitric oxide (NO) in the effects of low endotoxemia on gastric damage and blood flow has been evaluated in indomethacin‐treated rats.

Pretreatment (−1 h) with endotoxin (40 μg kg−1) reduced gastric damage induced by indomethacin (20 mg kg−1) in conscious rats.

Endotoxin prevented the reduction in gastric blood flow (laser Doppler flowmetry) induced by indomethacin in pentobarbital‐anaesthetised rats.

Pretreatment with an NO‐synthase (NOS) inhibitor (L‐NAME, 1 mg kg−1) reversed the protective effect of endotoxin on gastric blood perfusion.

Endotoxin did not modify the expression of mRNA for endothelial NOS or inducible NOS in the gastric corpus when evaluated 1 h postinjection. However, a 3.8‐fold increase in inducible NOS mRNA and a 61% reduction in endothelial NOS mRNA were observed in the gastric corpus 4 h after endotoxin administration.

Evaluation of both total and Ca2+‐dependent NOS activity by analysing the rate of conversion of L‐arginine to L‐citrulline in gastric corpus homogenates showed no differences between animals treated with endotoxin and those treated with saline 1 or 4 h beforehand. Ca2+‐independent NOS activity was almost non‐apparent in control as well as in endotoxin‐treated rats at all the time points analysed.

Low endotoxemia preserves blood perfusion and protects the gastric mucosa against the deleterious effects of indomethacin through the endogenous NO release. NO synthesis in response to endotoxin does not involve the inducible NOS, but probably depends on the post‐translational/biochemical regulation in vivo of a Ca2+‐dependent NOS, most probably endothelial NOS.

British Journal of Pharmacology (2003) 139, 263–270. doi:10.1038/sj.bjp.0705239
Mechanism of kinin release during experimental acute pancreatitis in rats: evidence for pro‐ as well as anti‐inflammatory roles of oedema formation
Authors: Griesbacher Thomas , Rainer Irmgard , Tiran Beate , Fink Edwin , Lembeck Fred , Peskar Bernhard A
Published: May 2003

Kinin B2 receptor antagonists or tissue kallikrein (t‐KK) inhibitors prevent oedema formation and associated sequelae in caerulein‐induced pancreatitis in the rat. We have now further investigated the mechanism of kinin generation in the pancreas.

Kinins were elevated in the pancreatic tissue already before oedema formation became manifest. Peak values (421±59 pmol g−1 dry wt) were reached at 45 min and remained elevated for at least 2 h; a second increase was observed at 24 h. Pretreatment with the B2 receptor antagonist icatibant abolished kinin formation, while post‐treatment was ineffective.

Total kininogen levels were very low in the pancreas of controls, but increased 75‐fold during acute pancreatitis. This increase was absent in rats that were pretreated with icatibant.

During pancreatitis, t‐KK‐like and plasma kallikrein (p‐KK)‐like activity in the pancreas, as well as trypsinogen activation peptide (TAP) increased significantly. Icatibant pretreatment further augmented t‐KK about 100‐fold, while p‐KK was significantly attenuated; TAP levels remained unaffected.

Endogenous protease inhibitors (α1‐antitrypsin, α2‐macroglobulin) were low in normal tissues, but increased 45‐ and four‐fold, respectively, during pancreatitis. This increase was abolished when oedema formation was prevented by icatibant.

In summary, oedema formation is initiated by t‐KK; the ensuing plasma protein extravasation supplies further kininogen and active p‐KK to the tissue. Concomitantly, endogenous protease inhibitors in the oedema fluid inhibit up to 99% of active t‐KK. Our data thus suggest a complex interaction between kinin action and kinin generation involving positive and negative feedback actions of the inflammatory oedema.

British Journal of Pharmacology (2003) 139, 299–308. doi:10.1038/sj.bjp.0705247
The neuromedin B receptor antagonist, BIM‐23127, is a potent antagonist at human and rat urotensin‐II receptors
Authors: Herold Christopher L , Behm David J , Buckley Peter T , Foley James J , Wixted William E , Sarau Henry M , Douglas Stephen A
Published: May 2003

The functional activity of the peptidic neuromedin B receptor antagonist BIM‐23127 was investigated at recombinant and native urotensin‐II receptors (UT receptors). Human urotensin‐II (hU‐II) promoted intracellular calcium mobilization in HEK293 cells expressing the human UT (hUT) or rat UT (rUT) receptors with pEC50 values of 9.80±0.34 (n=6) and 9.06±0.32 (n=4), respectively. While BIM‐23127 alone had no effect on calcium responses in either cell line, it was a potent and competitive antagonist at both hUT (pA2=7.54±0.14; n=3) and rUT (pA2=7.70±0.05; n=3) receptors. Furthermore, BIM‐23127 reversed hU‐II‐induced contractile tone in the rat‐isolated aorta with a pIC50 of 6.66±0.04 (n=4). In conclusion, BIM‐ 23127 is the first hUT receptor antagonist identified to date and should not be considered as a selective neuromedin B receptor antagonist.

British Journal of Pharmacology (2003) 139, 203–207. doi:10.1038/sj.bjp.0705251
Pharmacology and direct visualisation of BODIPY‐TMR‐CGP: a long‐acting fluorescent β2‐adrenoceptor agonist
Authors: Baker Jillian G , Hall Ian P , Hill Stephen J
Published: May 2003

Fluorescence techniques offer a way to circumvent several problems associated with many radioligand binding and functional assays and the need for large numbers of cells. Fluorescent ligands also offer the advantage of allowing real time direct visualisation of ligand – receptors interactions. A fluorescent analogue of CGP 12177 (BODIPY‐TMR‐CGP) has thus been evaluated as a β2‐adrenoceptor ligand in CHO‐K1 cells expressing the human β2‐adrenoceptor.

Studies of 3H‐cAMP accumulation showed that BODIPY‐TMR‐CGP stimulated an increase in cAMP accumulation and cyclic AMP response element (CRE)‐mediated gene transcription with an EC50 of 21–28 nM. Both of these responses were antagonised by the selective β2‐adrenoceptor antagonist ICI 118551.

Binding studies with 3H‐CGP 12177, and functional studies of CRE‐regulated gene transcription showed that the BODIPY‐TMR‐CGP interaction with the human β2‐adrenoceptor is of very long duration.

Visualisation of the binding of BODIPY‐TMR‐CGP to single living mammalian cells was clearly demonstrated by confocal microscopy and showed that this ligand was able to selectively label cell surface β2‐adrenoceptors in living CHO‐K1 cells transfected with the human β2‐adrenoceptor with an apparent KD of 27 nM. Studies with cells expressing a β2‐adrenoceptor–green fluorescent protein (GFP) fusion protein provided further strong evidence that BODIPY‐TMR‐CGP was binding to the β2‐adrenoceptor.

BODIPY‐TMR‐CGP is therefore a long‐acting fluorescent β2‐adrenoceptor agonist that can be used to label β2‐adrenoceptors in the plasma membrane of living cells.

British Journal of Pharmacology (2003) 139, 232–242. doi:10.1038/sj.bjp.0705287
Vaginal birth after Caesarean section: A survey of practice in Australia and New Zealand
Authors: Dodd Jodie , A. Crowther Caroline
Published: May 2003

Aims: Women with a single prior Caesarean section (CS) in a subsequent pregnancy will be offered either a planned elective repeat CS or vaginal birth after Caesarean (VBAC). Recent reports of VBAC have highlighted risks of increased morbidity, including uterine rupture, and adverse infant outcome. A survey of practice was sent to fellows and members of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists to determine current care for women in a subsequent pregnancy with a single prior CS, and to assess variations by length and type of obstetric practice.

Methods: Questions asked about the safety of VBAC, induction of labour with a uterine scar, and requirements to conduct VBAC and elective repeat CS.

Results: A total of 1641 surveys were distributed, with 1091 (67%) returned, 844 from practicing obstetricians (51% of college membership). Almost all respondents (96%) agreed or strongly agreed that VBAC should be presented as an option to the woman, varying from 90% where the indication for primary CS was breech, 88% for fetal distress, and 55% for failure to progress. Forty percent of respondents agreed or strongly agreed that VBAC was the safest option for the woman, and associated with fewer risks than CS. In contrast, 44% of respondents disagreed or strongly disagreed that VBAC was the safest option for the infant, and opinions varied as to whether risks of VBAC outweighed those of CS for the infant. Almost two‐thirds of practitioners would offer induction of labour to a woman with a prior CS in a subsequent pregnancy, one‐third indicating a willingness to use vaginal prostaglandins, and 77% syntocinon. Most respondents preferred to conduct VBAC in a level two or three hospital (86%); required the availability within 30 min of an anaesthetist (81%), a neonatologist (84%), and operating theatre (97%); recommended continuous electronic fetal heart rate monitoring (86%); intravenous access (90%); and routine group and hold (79%) during labour. For an elective repeat CS, most practitioners request routine blood for group and hold (78%), a neonatologist in theatre (77%), the use of an in‐dwelling urinary catheter (96%), and the use of intraoperative antibiotics (82%).

Conclusions: Most obstetricians indicated VBAC to be the safest option for the woman, but were less certain about benefits and risks for the infant. The consensus of practice is to present VBAC as an option and induce labour if needed. Vaginal birth after Caesarean is preferred in a level two or three hospital, with an anaesthetist, neonatologist and operating theatre available within 30 min. The use of continuous electronic fetal heart rate monitoring and intravenous access are recommended. In planned CS, a neonatologist in theatre is preferred, and an in‐dwelling urinary catheter and intraoperative antibiotics will be used.
Ankylosis and bone destruction of joints in type II collagen‐induced arthritis in different strains of mice
Authors: Ito Jun
Published: May 2003

Objective: To evaluate the differences in the clinical and histological findings in various strains of mice with collagen‐induced arthritis.

Methods: We induced arthritis in several strains of mice of DBA/1, B10.RIII, and B10.Q with bovine type II collagen. The arthritis was evaluated clinically and histologically.

Results: The incidence of arthritis was higher in DBA/1 mice than in B10.RIII and B10.Q mice. Severity in terms of the presence of ankylosis was greater in B10.RIII and B10.Q mice than in DBA/1 mice. Histological findings presented severe bone destruction and bony ankylosis in B10.RIII mice. At 22 weeks after injection of collagen, B10.RIII mice showed bony ankylosis of the ankle joints, in which new bone formations occurred at the corners of the joints.

Conclusion: Ankylosis and bone destruction were observed at higher rates in B10.RIII and B10.Q mice than in DBA/1 mice.
Five‐and‐a‐half year study of 107 patients with septic arthritis in a general hospital in Singapore
Authors: Rahman M Matiur , Leong Khai Pang , Edwards Christopher J , Chng Hiok Hee
Published: May 2003

Introduction: Septic arthritis (SA) damages synovial joints and causes considerable morbidity and mortality. We wanted to explore the patterns of presentation, risk factors, causative organisms and outcome of SA in Singapore. In particular, we were interested to see if increasing numbers of drug‐resistant organisms were changing the presentation and outcome of SA.

Materials and methods: Patients with SA were identified using the computerized discharge diagnosis records. We retrospectively reviewed the case records of 107 patients with SA admitted from January 1995 to June 2000 to the Tan Tock Seng Hospital, Singapore.

Results: Amongst the patients studied, 42% were above 60 years of age, 51.4% experienced fever and 47% demonstrated an elevated eythrocyte sedimentation rate. The knee joint was the commonest joint involved (64.5%). Pre‐existent joint disease was present in 27.1% and prosthetic joints in 11.2%. Skin infection preceded SA in 19.6% of individuals and large numbers had coexistent medical diseases (43%) with diabetes (29%) and chronic cardiovascular disease. Staphylococcus aureus was the leading causative organism (51.7% of synovial fluid cultures) and 22.6% of these were methicillin‐resistant Staphylococcus aureus (MRSA). Seven patients died (6.5%) and 62.3% had incomplete recovery. Using logistic regression, Staphylococcus aureus bacteraemia, isolation of Staphylococcus aureus from the synovial fluid and previous history of SA were shown to be independent risk factors for poorer outcome.

Conclusion: Septic arthritis remains an important cause of morbidity and mortality. We have identified clinical factors that may predict poorer outcomes in patients with SA.