Henning Lygre

Prosthodontic biomaterials and adverse reactions: a critical review of the clinical and research literature

Prosthodontic biomaterials include impression materials, luting cements, and restorative materials. They consist of metals and alloys, ceramics, and polymer materials and are retained in patients for <60 min or for decades. Oral release of compounds from biomaterials occurs, and adverse reactions may follow dental treatment. Especially in allergically vulnerable patients contact allergy may occur. There are reports from many different countries on contact allergy from gold/palladium alloys, components from polymer-based materials, chromium/cobalt alloys, and nickel. Notifications on adverse reactions in Norway, Sweden, and England are handled by a registry in which patient reactions and occupational exposure are recorded. Data from The Adverse Reaction Unit in Bergen and Umeaºhave been a most valuable basis in extending knowledge in a field of current interest in dentistry. A review of the clinical and research literature relating to prosthodontic biomaterials and adverse reactions shows that reliable methods seem necessary to expose the frequency of adverse reactions in general dentistry, including prosthodontic treatment.

Release and bioactivity of bone morphogenetic protein-2 are affected by scaffold binding techniques in vitro and in vivo

A low dose of 1μg rhBMP-2 was immobilised by four different functionalising techniques on recently developed poly(l-lactide)-co-(ε-caprolactone) [(poly(LLA-co-CL)] scaffolds. It was either (i) physisorbed on unmodified scaffolds [PHY], (ii) physisorbed onto scaffolds modified with nanodiamond particles [nDP-PHY], (iii) covalently linked onto nDPs that were used to modify the scaffolds [nDP-COV] or (iv) encapsulated in microspheres distributed on the scaffolds [MICS]. Release kinetics of BMP-2 from the different scaffolds was quantified using targeted mass spectrometry for up to 70days. PHY scaffolds had an initial burst of release while MICS showed a gradual and sustained increase in release. In contrast, NDP-PHY and nDP-COV scaffolds showed no significant release, although nDP-PHY scaffolds maintained bioactivity of BMP-2. Human mesenchymal stem cells cultured in vitro showed upregulated BMP-2 and osteocalcin gene expression at both week 1 and week 3 in the MICS and nDP-PHY scaffold groups. These groups also demonstrated the highest BMP-2 extracellular protein levels as assessed by ELISA, and mineralization confirmed by Alizarin red. Cells grown on the PHY scaffolds in vitro expressed collagen type 1 alpha 2 early but the scaffold could not sustain rhBMP-2 release to express mineralization. After 4weeks post-implantation using a rat mandible critical-sized defect model, micro-CT and Masson trichrome results showed accelerated bone regeneration in the PHY, nDP-PHY and MICS groups. The results demonstrate that PHY scaffolds may not be desirable for clinical use, since similar osteogenic potential was not seen under both in vitro and in vivo conditions, in contrast to nDP-PHY and MICS groups, where continuous low doses of BMP-2 induced satisfactory bone regeneration in both conditions. The nDP-PHY scaffolds used here in critical-sized bone defects for the first time appear to have promise compared to growth factors adsorbed onto a polymer alone and the short distance effect prevents adverse systemic side effects.

Leaching of organic additives from dentures in vivo

Samples of saliva were collected from subjects with dentures. These samples were collected both before the dentures were replaced and 1 week after the subjects had received their new dentures. Dibutylphthalate and phenyl benzoate were detected in the saliva samples with a gas-chromatography and a gas-chromatography/mass-spectrometry technique. We also quantified the dibutylphthalate in the saliva. In addition, in an in vitro study, we identified biphenyl leached from heat-cured denture base polymer plates. Our study suggests that subjects with dentures have higher contents of the above organic substances in saliva than subjects without dentures and that organic additives leach from new heat-cured dentures.

Leaching from denture base materials in vitro

Specimens made from denture base materials were leached in Ringer solution and in ethanol. The specimens comprised a heat-cured product processed in two different ways and two cold-cured materials. The organic compounds leaching from the specimens to the solutions were separated, identified, and quantified by a combined gas-chromatography and gas-chromatography/mass-spectrometry technique. Additives and degradation products, possibly made by free radical reactions, were released from the denture base materials. In Ringer solution only phthalates could be quantified. In ethanol solvent, biphenyl, dibutyl phthalate, dicyclohexyl phthalate, phenyl benzoate, and phenyl salicylate were quantified. In addition, copper was found in the ethanol solvent from one of the denture base materials. The amount of leachable organic compounds varies among different materials. Processing temperature influences the initial amount of leachable compounds.

Intramolecular hydrogen bonding in articaine can be related to superior bone tissue penetration: A molecular dynamics study

Local anesthetics (LAs) are drugs that cause reversible loss of nociception during surgical procedures. Articaine is a commonly used LA in dentistry that has proven to be exceptionally effective in penetrating bone tissue and induce anesthesia on posterior teeth in maxilla and mandibula. In the present study, our aim was to gain a deeper understanding of the penetration of articaine through biological membranes by studying the interactions of articaine with a phospholipid membrane. Our approach involves Langmuir monolayer experiments combined with molecular dynamics simulations. Membrane permeability of LAs can be modulated by pH due to a titratable amine group with a pKa value close to physiological pH. A change in protonation state is thus known to act as a lipophilicity switch in LAs. Our study shows that articaine has an additional unique lipophilicity switch in its ability to form an intramolecular hydrogen bond. We suggest this intramolecular hydrogen bond as a novel and additional solvent-dependent mechanism for modulation of lipophilicity of articaine which may enhance its diffusion through membranes and connective tissue.

Interaction of ibuprofen with eukaryotic membrane lipids.

With the versatility of the molecular mechanism of amphiphilic drugs there is the possibility that ibuprofen could interact with eukaryotic model membrane lipids. Using the Langmuir technique, we first determined the pressure/molecular area isotherms of glycerophospholipids monolayers at 37°C, and, second, using differential scanning calorimetry (DSC), phase transition parameters in liposomes of the same lipids. Ibuprofen interacted in a concentration‐independent manner with monolayers of saturated phosphatidylcholines (PC, i.e. markers of the outer membrane leaflet of eukaryotic cells). Ibuprofen was found to interact with liposomes of saturated and unsaturated phosphatidylcholines and ‐serines (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). A lowering of the lipid melting temperature (Tm) and a change of enthalpy (ΔH) of the gel to liquid‐crystalline phase transitions of liposomes were detected.

Leaching of additives and degradation products from cold-cured orthodontic resins

Unstimulated saliva was collected from orthodontic patients and subjected to combined gas-chromatography and gas-chromatography/mass-spectrometry analyses. Saliva was collected before insertion of removable orthodontic appliances made of cold-cured resins. Saliva was then collected 1-2 months after insertion of the appliances and 1 week after they had been removed. Phenyl benzoate (PB) and phenyl salicylate (PS) were identified in pooled saliva samples from patients wearing the appliances. Biphenyl and 2-methoxy-4-hydroxy-benzophenone in addition to PB and PS were identified in a study with in vitro specimens made of orthodontic resin. The leaching of compounds from these test specimens processed by a powdering technique and a pre-mix technique was compared.

Interaction of articaine hydrochloride with prokaryotic membrane lipids

Objective. Local anesthetics are the most commonly used drugs in dentistry, with a wide range of effects, including antimicrobial activity. High antimicrobial effects have recently been reported on oral microbes from articaine hydrochloride, revealed by the minimum inhibitory concentration and minimal bactericidal concentration. Additionally, articaine has recently been used as an alkaline component in endodontic materials with a proposed antibacterial activity. However, the detailed mechanisms of action have not been discussed. Material and Methods. We determined the Langmuir surface pressure/molecular area isotherms of prokaryotic lipid monolayers, as well as the phospholipid phase transitions, by employing differential scanning calorimetry on unilamellar prokaryotic liposomes (bilayers). Results. Articaine hydrochloride was found to interact with the prokaryotic membrane lipids in both monolayers and bilayers. An increase of the phospholipid molecular area of acidic glycerophospholipids as well as a decrease in phase transition temperature and enthalpy were found with increasing articaine hydrochloride concentration. The thermodynamic changes by adding articaine hydrochloride to prokaryotic membrane lipids are potentially related to the effects observed from antimicrobial peptides resulting from membrane insertion, aggregate composition, pore formation, and lysis. Conclusion. Interaction of articaine hydrochloride with prokaryotic membrane lipids is indicated. Hence, further research is necessary to gain insight into where these compounds exert their effects at the molecular level.

A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students

Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher’s role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components.

Management of periodontal disease in patients using calcium channel blockers – gingival overgrowth, prescribed medications, treatment responses and added treatment costs

OBJECTIVES Gingival overgrowth (GO) is an adverse drug reaction in patients using calcium channel blockers (CCBs). Little is known about the effects of CCBs on the management of periodontal diseases. The aim of this study was to assess how the use of CCBs affects the long-term supportive treatment and outcomes in patients undergoing periodontal therapy. METHODS All patients using CCBs during the initial treatment and/or the supportive periodontal therapy (SPT) were selected from a periodontal practice. Patients were scored using a Gingival Overgrowth Index (GOI). The effects of CCB types and dosages were assessed in terms of the frequency and the severity of GO, treatment responses, substitutions and extra treatment costs. Mean values, Standard Deviation (SD) and range were calculated. The Mann-Whitney test was used to assess statistically significant differences (p < 0.05) for GO between patients with good and poor oral hygiene, differences between before and after terminating or replacing the CCBs, possible differences between drug dosages (Dihydropyridine 5 mg and 10 mg) and differences between three drug combinations (CCB and inhibitors of the renin-angiotensin system (IRAS), CCB and non-IRAS, CCB and statins). RESULTS One hundred and twenty-four patients (58 females, 66 males, 4.6% of the patient population) were using CCBs. 103 patients were assessed. Average age was 66.53 years (SD. 9.89, range 42-88) and the observation time was 11.30 years (SD 8.06, range 1-27). Eighty-nine patients had GO, 75 of these required treatment for GO. Terminating or replacing with alternatives to CCBs resulted in significant decreases in GO (p = 0.00016, p = 0.00068) respectively. No differences were found between good and poor oral hygiene (p = 0.074), drug dosages or the various drug combinations. Surgical treatment was more effective than non-surgical treatment in controlling the GO. Long-term tooth loss was 0.11 teeth per patient per year. Forty-two patients needed re-treatments for GO, resulting in an extra life cost per patient of €13471 (discounted €4177). CONCLUSION The majority of patients (86.4%) using CCBs experienced GO. 47.2% of these experienced recurrence(s) of GO during the SPT and needed re-treatments with resulting added costs. The long-term tooth loss was considerably higher for patients using CCBs than for other patients groups from the same practice setting.