Changes in Dentists' Prescribing Patterns in Norway 2005-2015.

BACKGROUND: There is scant knowledge of dentists' total prescribing patterns, and little is published on this internationally. The Norwegian Prescription Database (NorPD) includes data on all dispensed prescription medication in Norway from 2004 and can be used to investigate how dentists' prescribing has changed over time. There are few Norwegian guidelines supporting dentists' prescribing, and Norwegian legislation on dentists' prescribing rights leaves room for interpretation. The aim of this study was therefore to give an overview of all prescribing from dentists in Norway in the period 2005 to 2015 and to identify trends in their prescribing pattern over this time span. We also give characteristics of the prescribing dentists. METHODS: The study had a retrospective pharmacoepidemiologic design. Data on all medication prescribed by dentists and dispensed from Norwegian pharmacies in the time period 2005 to 2015 were extracted from the NorPD. Changes over time in the prescribers, patients, and medications are reported. RESULTS: There was an increase of 50% in total number of prescriptions from dentists in Norway from 2005 to 2015; adjusted for the growth in population, there was a 33% increase. The majority of prescriptions from dentists were for antibiotics and analgesics; however, the data reveal that the dentists prescribed from all major therapeutic groups. Dentists increased antibiotic prescribing in a period when total antibiotic prescribing in Norway decreased. CONCLUSIONS: Our study finds antibiotics and analgesics dominate prescriptions from Norwegian dentists and shows an increase in use over time. It highlights the need for creating evidence-based prescribing guidelines for dentists and for ensuring that existing guidelines are implemented.

Serum Analysis in Patients with Temporomandibular Disorders: A Controlled Cross-Sectional Study in Norway.

Temporomandibular disorder (TMD) is characterized by pain and dysfunction in the temporomandibular join (TMJ) and the masticatory apparatus. Associations with autoimmune diseases, inflammatory conditions, and nutrition deficiencies have been reported in previous studies of TMD patients. To evaluate essential proteins, hormones, electrolytes, and vitamins in serum from TMD patients, a standard blood sample analysis was performed in 60 TMD patients and 60 healthy controls matched for age and gender, retrieving 19 different analyses. We found that TMD patients had significantly higher values of hemoglobin (p=0.036), cobalamin (p=0.023), albumin (p=0.005), parathyroid hormone (PTH) (p=0.038), and vitamin D (p=0.005), and significantly lower values of creatinine (p=0.006) and potassium (p=0.011), compared to controls. In the TMD group, most of the determinants had a wider range, and several subjects, compared to the control group, had values outside the normal reference area. However, most of the TMD patients and controls had values within normal biological range. Our findings could not associate any severe systemic disease, malnutrition, or systemic inflammation with the TMD. Results from our study suggest that serum analyses should neither be used as a biomarker of TMD nor a diagnostic tool for an individual subject with TMD.

Efficacy of copolymer scaffolds delivering human demineralised dentine matrix for bone regeneration.

Poly(L-lactide-co-ε-caprolactone) scaffolds were functionalised by 10 or 20 µg/mL of human demineralised dentine matrix. Release kinetics up to 21 days and their osteogenic potential on human bone marrow stromal cells after 7 and 21 days were studied. A total of 390 proteins were identified by mass spectrometry. Bone regeneration proteins showed initial burst of release. Human bone marrow stromal cells were cultured on scaffolds physisorbed with 20 µg/mL and cultured in basal medium (DDM group) or physisorbed and cultured in osteogenic medium or cultured on non-functionalised scaffolds in osteogenic medium. The human bone marrow stromal cells proliferated less in demineralised dentine matrix group and activated ERK/1/2 after both time points. Cells on DDM group showed highest expression of IL-6 and IL-8 at 7 days and expressed higher collagen type 1 alpha 2, SPP1 and bone morphogenetic protein-2 until 21 days. Extracellular protein revealed higher collagen type 1 and bone morphogenetic protein-2 at 21 days in demineralised dentine matrix group. Cells on DDM group showed signs of mineralisation. The functionalised scaffolds were able to stimulate osteogenic differentiation of human bone marrow stromal cells.

Temporomandibular Disorders Related to Stress and HPA-Axis Regulation.

Temporomandibular disorders (TMDs) are characterized by pain and dysfunction in the masticatory apparatus and the temporomandibular joint (TMJ). Previous trauma, stress symptoms, psychosocial impairment, and catastrophizing have been related to TMD. To assess if the hypothalamic-pituitary-adrenal (HPA) axis is upregulated in TMD patients, we performed a cross-sectional study with saliva from 44 TMD patients and 44 healthy sex- and age-matched controls for cortisol (F) and cortisone (E) with liquid chromatography-tandem mass spectrometry. Furthermore, we calculated the F/E ratio for the evaluation of 11ß-hydroxysteroid dehydrogenase activity. We also assessed anxiety/depression and pain catastrophizing scores from a questionnaire that participants completed prior to the examination. We found that F (P=0.01), E (P=0.04), the F/E ratio (P=0.002), and the sum of glucocorticoids (E + E) in saliva (P=0.02) were significantly higher in the TMD group. Anxiety/depression and catastrophizing scores were also significantly higher in the TMD group (P < 0.0001). Our findings indicate that patients with TMDs may have an upregulated HPA axis with higher F secretion from the adrenal cortex. Anxiety/depression and pain catastrophizing scores were significantly higher in the TMD group, and psychological factors may contribute to chronic upregulation of the HPA axis.

Dental providers and pharmacists: a call for enhanced interprofessional collaboration.

Reports concerning medication discrepancies in dental records indicate that the concept of interprofessional collaboration between the dental team and pharmacists should be considered at all educational levels in dentistry and pharmacy. Inclusion of oral health as a therapeutic area in didactic pharmacy curricula is needed. Early exposure of dental students and student pharmacists to collaborative practices through interprofessional educational experiences may create a higher degree of awareness of the role of each profession and the potential to improve patient outcomes. Furthermore, efforts are needed to develop a systematic approach for medication review and reconciliation in dental practice to obtain accurate medication lists, potentially by utilising health information technology.

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.

Exploring the relationship between childhood adversity and oral health: An anecdotal approach and integrative view.

During the past two decades, increasing recognition has been given to a relationship between oral health and systemic diseases. Associated systemic conditions include cardiovascular disease, diabetes, low birth weight and preterm births, respiratory diseases, rheumatoid arthritis, obesity, osteoporosis, and, in particular among oral conditions, periodontal disease. Low-grade inflammation is a common denominator linking these disorders. Applying an anecdotal approach and an integrative view, the medical and dental histories of two women document increasing ill health subsequent to incidences of maltreatment and sexual abuse, including oral penetration, at an early age. Comprehensive oral rehabilitation was required in both cases. These cases open for medical insight with regard to their implicit patho-physiology, when integrated with current evidence from neuroscience, endocrinology, and immunology, converging in the concepts of allostasis and allostatic load. In cases such as those presented in this paper, primary care physicians (family doctors, General Practitioners) and dentists may be the first to identify an etiological pattern. This report underlines the importance of increased and enhanced multidisciplinary research cooperation among health professionals. Our hypothesis is that childhood adversity may affect all aspects of human health, including adult oral health.

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.

Resolvin D1 protects periodontal ligament.

Resolution agonists are endogenous mediators that drive inflammation to homeostasis. We earlier demonstrated in vivo activity of resolvins and lipoxins on regenerative periodontal wound healing. The goal of this study was to determine the impact of resolvin D1 (RvD1) on the function of human periodontal ligament (PDL) fibroblasts, which are critical for wound healing during regeneration of the soft and hard tissues around teeth. Primary cells were cultured from biopsies obtained from three individuals free of periodontal diseases. Peripheral blood mononuclear cells were isolated by density gradient centrifugation from whole blood of healthy volunteers. PGE2, leukotriene B4 (LTB4), and lipoxin A4 (LXA4) in culture supernatants were measured by ELISA. The direct impact of RvD1 on PDL fibroblast proliferation was measured and wound closure was analyzed in vitro using a fibroblast culture "scratch assay." PDL fibroblast function in response to RvD1 was further characterized by basic FGF production by ELISA. IL-1ß and TNF-α enhanced the production of PGE2. Treatment of PDL cells and monocytes with 0.1-10 ng/ml RvD1 (0.27-27 M) reduced cytokine induced production of PGE2 and upregulated LXA4 production by both PDL cells and monocytes. RvD1 significantly enhanced PDL fibroblast proliferation and wound closure as well as basic FGF release. The results demonstrate that anti-inflammatory and proresolution actions of RvD1 with upregulation of arachidonic acid-derived endogenous resolution pathways (LXA4) and suggest resolution pathway synergy establishing a novel mechanism for the proresolution activity of the ω-3 docosahexaenoic acid-derived resolution agonist RvD1.

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.

Detection and quantification of monomers in unstimulated whole saliva after treatment with resin-based composite fillings in vivo.

Resin-based dental restorative materials contain allergenic methacrylate monomers, which may be released into saliva after restorative treatment. Monomers from resin-based composite materials have been demonstrated in saliva in vitro; however, studies analyzing saliva after restorative therapy are scarce. The aim of this study was to quantify methacrylate monomers in saliva after treatment with a resin-based composite filling material. Saliva was collected from 10 patients at four start points--before treatment, and 10 min, 24 h, and 7 d after treatment--and analysed by combined chromatography/mass spectrometry. The monomers bisphenol-A diglycidyl methacrylate (Bis-GMA), 2-hydroxyethyl methacrylate (HEMA), and urethane dimethacrylate (UDMA) were detected and quantified in the samples collected shortly (10 min) after treatment. The amounts detected ranged from 0.028 to 9.65 µg ml(-1) for Bis-GMA, from 0.015 to 0.19 µg ml(-1) for HEMA, and from 0.004 to 1.2 µg ml(-1) for UDMA. Triethyleneglycol dimethacrylate (TEGDMA) was detected in four of the samples. Ethoxylated bisphenol-A dimethacrylate (Bis-EMA) was not detected. Monomers were not detected in saliva samples collected before treatment, or 24 h or 7 d after treatment, with the exception of one sample, 24 h after treatment, in which HEMA was detected. In conclusion, monomers from the investigated resin-based composite and adhesive system were present in saliva shortly after treatment. One week after treatment, no monomers could be detected in patients' saliva samples.

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 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.

Articaine interaction with DSPC bilayer: a 13C and 31P solid-state NMR study.

Articaine hydrochloride, 4-methyl-3-(2-[propylamino]propionamido)-2-thiophenecarboxylic acid, methyl ester hydrochloride, is a local anaesthetic commonly used in dentistry, and is classified as an amide local anaesthetic. Solid-state (13)C and (31)P NMR were used to investigate the uncharged articaine species (sample pH 10.0) when interacting with distearoylphosphatidylcholine (DSPC) model membranes. The DSPC phospholipid bilayer was studied at four different molar ratios of articaine, 10, 25, 40, and 55 mol%, respectively. The articaine concentration-dependent decrease in the DSPC bilayer gel-to-liquid-crystalline phase-transition temperature demonstrates substantial articaine interaction with this bilayer. A DSPC bilayer contains a large hydrophobic core and the (13)C and (31)P NMR spectra of the 40 mol% articaine-containing sample demonstrate a disturbance in the molecular packing of the polar bilayer region that extends into the hydrophobic region, evidenced by carbon 2 and 3 of the stearoyl acyl chains. Observed (31)P and (13)C NMR spectral changes when articaine is increased from 40 to 55 mol%, suggest formation of articaine aggregates and decrease in DSPC bilayer perturbation at the latter articaine level.

Quantitative analysis of TEGDMA and HEMA eluted into saliva from two dental composites by use of GC/MS and tailor-made internal standards.

OBJECTIVES: The use of resin-based dental restorative materials is rapidly increasing, concurrently the biocompatibility of the materials is under investigation. Attention has been placed on studies addressing the cytotoxic, genotoxic and estrogenic potential of these materials. Therefore, the degree of exposure to eluted compounds from the dental materials is of high interest. The aim of this study was to assess the amounts of 2-hydroxyethyl methacrylate (HEMA) and triethyleneglycol dimethacrylate (TEGDMA), released from two composites, eluting into human saliva. To improve the method of quantification, three tailor-made internal standards were synthesized. METHODS: Specimens made from two composites (Tetric EvoCeram and Filtek Z250) were polymerized and immersed in human saliva for 24h. Eluted TEGDMA and HEMA were identified and quantified. The quantitative analyses were performed by use of combined gas chromatography-mass spectrometry (GC/MS) with tailor-made internal standards synthesized by dissolving HEMA or TEGDMA in methanol and reducing the double bond of the methacrylate group by hydrogenation with 1H2 and 2H2 (D2) gas. RESULTS: HEMA was released from both materials, whereas TEGDMA eluted from Filtek Z250 only. Full scan GC-MS analysis of each tailor-made internal standard demonstrated one peak only, which was well separated from the corresponding analyte's peak and with no traces of HEMA or TEGDMA. SIGNIFICANCE: The quantification method seems well suited for in vivo analysis, and the three standards synthesized represent an improved tool for quantification of the eluted monomers. The synthesis may be applied to other methacrylate monomers to produce tailor-made standards for quantification.

Quantification of organic eluates from polymerized resin-based dental restorative materials by use of GC/MS.

Residual monomers, additives and degradation products from resin-based dental restorative materials eluted into the oral cavity may influence the biocompatibility of these materials. Emphasis has been placed on studies addressing cytotoxic, genotoxic and estrogenic potential of these substances. A prerequisite for analyzing the potential of exposure to eluted compounds from dental materials is reliable quantification methods, both real time and accelerated measurements. The purpose of the present study was to quantify nine eluates; 2-hydroxyethyl methacrylate (HEMA), hydroquinone monomethyl ether (MEHQ), camphorquinone (CQ), butylated hydroxytoluene (BHT), ethyl 4-(dimethylamino)benzoate (DMABEE), triethylene glycoldimethacrylate (TEGDMA), trimethylolpropane trimethacrylate (TMPTMA), oxybenzone (HMBP) and drometrizole (TIN P) leaching from specimens of four commonly used resin-based dental materials in ethanol and an aqueous solution. All analyses were performed by use of GC/MS, each component was quantified separately and the results presented in microg mm(-2). This study has shown that elution from various materials differs significantly, not only in the types of eluates, but also regarding amounts of total and of single components. A high amount of HMBP, a UV stabilizer with potential estrogenic activity, was detected from one material in both solutions.

The coinitiator DMABEE induces death by apoptosis and necrosis in human monoblastoid cells.

4-N,N-Dimethyl amino benzoic acid ethylester (DMABEE), a leachable lipophilic component of polymer-based dental-filling materials, has been shown to interact with cell membrane phospholipids, such as phosphatidylcholine and phosphatidylserine (PS). One marker of cellular death by apoptosis is the change in architecture of the plasma membrane involving the translocation of the negatively charged PS from the inner to the outer leaflet of the cell membrane. We therefore hypothesized that DMABEE has the potential to induce apoptosis. The necrosis inducing potential was also investigated. To test our hypothesis human monoblastoid U-937 cells were exposed to 10, 20, 40, 80, 120, 160, and 200 microM of DMABEE for 24, 48, and 72 h. At the culture end-points apoptotic and necrotic cells were detected by flow cytometry. DMABEE enhanced cell death by apoptosis and necrosis in U-937 cells in a dose-dependent fashion. The data support our hypothesis that DMABEE triggers death-signaling pathways.

Interaction of triclosan with eukaryotic membrane lipids.

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 degrees 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.

Identification of organic eluates from four polymer-based dental filling materials.

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 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 degrees 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 (deltaH) of the gel to liquid-crystalline phase transitions of liposomes were detected.