The dental resin monomers HEMA and TEGDMA have inhibitory effects on osteoclast differentiation with low cytotoxicity.

The dental resin monomers 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) are released from the resin matrix due to unpolymerized monomers; once released, they influence various biological functions and the viability of cells in the oral environment. Although HEMA and TEGDMA have various effects on cells, including inflammation, inhibition of cell proliferation or differentiation, and apoptosis, the effects of these monomers on osteoclasts remain unknown. In this study, we investigated the effects of HEMA and TEGDMA on osteoclast differentiation of bone marrow-derived macrophages or murine monocytic cell line RAW-D. Both HEMA and TEGDMA inhibited osteoclast formation and their bone-resorbing activity at non-cytotoxic concentrations. Moreover, HEMA and TEGDMA decreased the expression of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), a master regulator of osteoclast differentiation, and of osteoclast markers that are transcriptionally regulated by NFATc1, including Src and cathepsin K. Regarding their effects on signaling pathways involved in osteoclast differentiation, HEMA impaired the phosphorylation of extracellular signal-regulated kinase and Jun N-terminal kinase, whereas TEGDMA attenuated the phosphorylation of Akt and Jun N-terminal kinase. Thus, HEMA and TEGDMA inhibit osteoclast differentiation through different signaling pathways. This is the first report on the effects of the monomers HEMA and TEGDMA on osteoclasts. Copyright © 2017 John Wiley & Sons, Ltd.

Repeated dose toxicity study of Vibrio cholerae-loaded gastro-resistant microparticles.

CONTEXT: Microencapsulation of antigens has been extensively studied over the last decades aiming at improving the immunogenicity of vaccine candidates. OBJECTIVE: Addressing microparticles (MPs) toxicity in rats. MATERIAL AND METHODS: Spray-dried Eudragit® L 30 D-55 MPs and Eudragit® L 30 D-55 alginate MPs were elaborated and characterized. MPs obtained were administered to rats, three groups were defined: G1, control group; G2, administered with Vibrio cholerae (VC)-loaded MPs; G3, receiving VC-loaded alginate MPs. Animals received three vaccine doses. Body weight, food and water intake were controlled during the study. Haematological parameters, vibriocidal titres, organ weight and histology in necropsy were also analyzed. RESULTS: All animals grew healthy. Body weight gain, food and water intake and haematological parameters remained within physiological values, showing no treatment-related differences. Moreover, organ weight changes were not detected and animals developed protective vibriocidal titres. CONCLUSION: VC-loaded MPs and VC-loaded alginate MPs have proved to be safe and effective in the assessed conditions.

[Allergies to dental materials and effectiveness of treatment in the north-eastern region of Hungary]. / Fogászati anyagokkal szemben kialakuló allergiás megbetegedések és ellátásuk hatékonyságának vizsgálata az észak-alföldi régióban.

The recognition and treatment of allergy is a great challenge for all fields of medicine. The high prevalence of allergic reactions to dental materials and the related financial burden of their treatment make investigation of this disease very important. Our investigation was carried out on patients assigned to our outpatient department for dental allergy test between 1996 and 1998. We determined the distribution of gender and age among the allergic patients in the examined population. We also studied the prevalence of allergic reactions to different dental allergens and the distribution of dental allergens. In a follow-up study we determined the proportion of those patients, who were retreated in conformity with the results of epicutan tests and we followed up the positive effects of these treatments. We have found that dental allergy occurred five times more frequently in women (84%) than in men (16%) and the most affected age group was between 20 to 39 and 40-49 years (31%). Seventy-five percent of the patients suffered from a combination of metal and polymer allergy. The most frequent metal allergen was TEGDMA (triethylene glycol dimethacrylate) (49.7%). The suggested treatment plan was carried out in 63% of the allergic patients. The applied treatment was successful in 48% of these cases. We experienced that 48% of these patients got rid of their earlier signs and symptoms.

High frequency of false-positive reactions in attempted patch testing with acrylate/methacrylate mixes.

BACKGROUND: Although acrylate/methacrylate allergy has been frequently reported, until now patch testing with this group of allergens has been unwieldy, requiring the application of large supplementary series in most centres. OBJECTIVES: To formulate and evaluate two mixes of acrylate/methacrylate allergens in three centres (Malmö, Singapore, and Leuven). PATIENTS/MATERIALS/METHODS: All patients tested with the baseline series during the study period were also patch tested with the mixes. Mix 1 consisted of: triethyleneglycol diacrylate (TREGDA) 0.1% wt/wt, 2-hydroxyethyl methacrylate (2-HEMA) 1.0% wt/wt and ethyleneglycol dimethacrylate 1.0% wt/wt in petrolatum. Mix 2 consisted of: TREGDA 0.1% wt/wt and 2-HEMA 2.0% wt/wt in pet. The separate components of the two mixes were also tested simultaneously. RESULTS: There were 25 (5 males; 20 females) positive reactions to mix 1 with 16 in Malmö, 8 in Singapore, and 1 in Leuven. Positive reactions to mix 2 were seen only in Malmö, in 8 female patients. Thus, the positive reaction rate for mix 1 was 8.3% overall (Malmö 7.7%, Singapore 18.6%, and Leuven 2.1%), and that for mix 2 was 2.7% overall (Malmö 3.8%, Singapore 0%, and Leuven 0%). Of the 16 positive reactions to mix 1 in Malmö, only 4 were considered to be true allergic reactions, as the component allergen testing gave totally negative results in 12/16. For mix 2, only 3/8 positive reactions were considered to be true allergic reactions, as the component testing was negative in 5/8. Many doubtful (10-20%) and positive but non-allergic reactions were recorded, leading to early termination of the study. CONCLUSIONS: Although this was an unsuccessful attempt to formulate an acrylate/methacrylate mix, our experience will be useful for those embarking on future attempts to do this.

Nicotine delivery and subjective effects of Swedish portion snus compared with 4 mg nicotine polacrilex chewing gum.

INTRODUCTION: Snus availability has been claimed to have contributed to the low rates of smoking among Swedish men and made possible the transfer to a less harmful form of nicotine dependence. METHODS: Fourteen cigarette smokers were randomly assigned to 2 types of 1 g Swedish portion snus and 4 mg nicotine polacrilex (NP) chewing gum in open-label, single-dose crossover study. Nicotine delivery and pharmacokinetics were estimated, and self-reports of subjective effects were obtained using Visual Analogue Scales (VASs). RESULTS: Extracted dose from the NP gum averaged 2.56 mg compared with 2.12 and 2.18 mg, respectively, for Swedish portion snus. This resulted in a slightly larger area under the curve (AUC) for the NP chewing gum. The rise of the nicotine plasma concentration was faster for Swedish snus. Median T(max) was shorter, 30 min for snus compared with 45 min for the NP gum. The lower C(max) of NP gum compared with the snus products in spite of larger AUC may be explained by slower absorption from the chewing gum. The faster absorption of nicotine from Swedish portion snus was mirrored in a higher VAS score for "head rush." Craving/urges to smoke decreased similarly for all treatments. Salivation and throat burn were rated higher for the 4 mg NP gum compared with both types of snus. CONCLUSIONS: Swedish snus produced higher maximum blood nicotine concentration in shorter time and with a quicker onset of "head rush" compared with 4 mg NP chewing gum in spite of a smaller extracted dose. The quicker onset of "head rush" and supposedly higher satisfaction from snus may partly explain the widespread use of snus for stopping smoking in Sweden.

Polymethylmethacrylate-assisted ventral discectomy: rate of pseudarthrosis and clinical outcome with a minimum follow-up of 5 years.

BACKGROUND: Polymethylmethacrylate (PMMA) assisted ventral discectomy has been criticized for high rates of graft migration and pseudarthrosis when compared with various other fusion procedures for the treatment of cervical degenerative disc disease (DDD), therefore rendering it not the preferred choice of treatment today. Recently however spine surgery has been developing towards preservation rather than restriction of motion, indicating that fusion might not be necessary for clinical success. This study presents a long term comparison of clinical and radiological data from patients with pseudarthrosis and solid arthrodesis after PMMA assisted ventral discectomy was performed. METHODS: From 1986 to 2004 416 patients underwent ventral discectomy and PMMA interposition for DDD. The clinical and radiological outcome was assessed for 50 of 127 eligible patients after a mean of 8.1 years. Based on postoperative radiographs the patients were dichotomized in those with a pseudarthrosis (group A) and those with solid arthrodesis (group B). RESULTS: Pseudarthrosis with movement of more than 2 of the operated segment was noted in 17 cases (group A). In 33 cases no movement of the vertebral segment could be detected (group B). The analysis of the clinical data assessed through the neck disability index (NDI), the visual analogue scale (VAS) of neck and arm pain and Odom's criteria did not show any significant differences between the groups.Patients from group B showed a trend to higher adjacent segment degeneration (ASD) than group A (p = 0.06). This correlated with the age of the patients. CONCLUSIONS: PMMA assisted discectomy shows a high rate of pseudarthrosis. But the clinical long-term success does not seem to be negatively affected by this.

Dental resin monomers induce early and potent oxidative damage on human odontoblast-like cells.

Resin-based dental materials consist of filler particles and different monomers that are light cured in situ to re-establish dental function and aesthetics. Due to the degree of conversion of adhesive polymers, the monomers triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are released in relatively high amounts and are susceptible to degradation, acting as bioactive compounds and affecting cell and tissues. This study aimed to assess the effect of HEMA and TEGDMA exposure on metabolic activity, membrane integrity, and cell survival of human odontoblast-like cell (hOLCs). Exposure to resin monomers for 24 h induced major changes in cell membrane integrity, metabolic activity, and survival, which were measured by the calcein method and lactate dehydrogenase release. Increased and early reactive oxygen species (ROS) production was observed leading to degradative oxidation of membrane lipids identified as malondialdehyde production. Severe alteration in mitochondria occurred due to transmembrane mitochondrial potential collapse, possibly inducing activation of apoptotic cell death. hOLCs exposure to resin monomers modified the cell redox potential, with consequences on membrane permeability and integrity, including mitochondrial function. Lipid peroxidation appears to be a key phenomenon for the membrane structures oxidation after HEMA and TEGDMA exposure, leading to cell death and cytotoxicity. hOLCs respond early by differential induction of adaptive mechanisms to maintain cell homeostasis. Modulation of oxidative stress-induced response involves the regulation of genes that encode for antioxidant proteins such as catalase and heme oxygenase-1; regulation that functions as a critical protection mechanism against oxidative cell damage induced by HEMA and TEGDMA. Ascorbic acid as an antioxidant substance mitigates the oxidative damage associated with exposure to monomers.

Oral ulceration due to chronic use of Nicorette gum: case report.

Oral ulceration is a common presentation in a dental clinic. These ulcers may be acute or chronic, based on the duration of symptoms. The etiology of oral ulceration can range from trauma to squamous cell carcinoma. It is the responsibility of the dentist to differentiate the various etiologies of oral ulceration for proper management. This case report is presented to remind dentists that the long-term use of Nicorette gum should be considered in the differential diagnosis of chronic oral ulcers.

The Rising Incidence of Allergic Contact Dermatitis to Acrylates.

BACKGROUND: Allergic contact dermatitis (ACD) caused by (meth)acrylates used in nail products is being increasingly reported in nail technicians and consumers. OBJECTIVES: The aim of the study was to assess the incidence of sensitization to (meth)acrylates in technicians and users of nail products with ACD, referred for patch testing in a tertiary center, during the last 10 years. METHODS: All patients with ACD, who reported a profession associated with cosmetic nail procedures or use of such services and were referred for patch tests in our department between January 2009 and December 2018, were identified. The incidence of positive sensitization to (meth)acrylates was assessed. RESULTS: Contact allergy to 1 or more (meth)acrylates was found in 116 (74.4%) of 156 nail technicians or nail product users, all women. One hundred thirty-eight (88.5%) were occupationally exposed, and 18 (11.5%) were consumers. In addition, there was a statistically significant increase in (meth)acrylate ACD during 2014-2018 (100/127 cases [79%]) when compared with 2009-2013 (16/29 cases [55%]). The most common sensitizer among the 156 allergic individuals was ethylene glycol dimethacrylate, which was positive in 113 cases (72.4%), and among patients with acrylate-positive patch test, the rate was 97.4%. CONCLUSIONS: Our experience confirms the worldwide changing landscape of rising (meth)acrylate sensitization in nail technicians and nail products users with ACD. Efforts to improve prevention are needed, and clinicians should have a high index for suspicion in this occupational group.

The spectrum of adverse reactions after treatment with injectable fillers in the glabellar region: results from the Injectable Filler Safety Study.

BACKGROUND: For the glabellar region, severe partly vascular adverse events have been reported after treatment with injectable fillers. METHODS AND MATERIALS: For this study, data from the Injectable Filler Safety Study, a German-based registry for those reactions, was analyzed to characterize adverse events seen in the glabellar region. Patients were analyzed descriptively. RESULTS: Forty of 139 registered patients reported adverse events in the glabellar region. All patients were female, with an average age of 52.3. Nineteen patients with adverse reactions to hydroxyethylmethacrylate (HEMA) and ethylmethacrylate (EMA) in a fixed combination with hyaluronic acid (HA) and 10 patients with adverse reactions to different hyaluronic acid products were reported; five patients reacted to poly-L-lactic acid (PLA). The most common adverse reactions to HEMA/EMA in HA and PLA were nodules and hardening. In HA-treated patients, erythema and inflammation, swelling, and pain were most frequent. The adverse reactions to HEMA/EMA in HA were severe in 50% of the patients. Severe adverse reactions were found to a lesser extent in patients treated with HA and PLA. Potential vascular complications were documented in only two patients. CONCLUSION: Adverse reactions seen in the glabella are overwhelmingly product associated and to a lesser extent location associated. Vascular complications with necrosis and ulceration were rare.

TEGDMA releasing in resin composites with different filler contents and its correlation with mitochondrial mediated cytotoxicity in human gingival fibroblasts.

Compositions of resin composite exhibit cytotoxicity, especially Triethylene-glycol-dimethacrylate (TEGDMA), yet the underlying mechanisms and its relationship with filler content are poorly understood. Here, specimens of five composites (VITA LC, VITA ZETA, Z350, Filtek P60, and AP-X), containing different filler size and weight, were immersed into culture medium for 72 h. After TEGDMA quantification, the resin composite eluates were used to incubate HGFs. Cellular viability was evaluated. Total reactive oxygen species (ROS) and mitochondrial ROS were detected to assess oxidative stress. Adenosine triphosphate and cytochrome c oxidase (CcO) activity, mitochondrial membrane potential and morphology, mitochondrial biogenesis regulators were analyzed to evaluate mitochondrial functions. Results showed that TEGDMA release negatively correlated to filler size and weight of tested composites. Although cell viability reduction was not significant, total and mitochondrial ROS production showed a positive relationship with the amount of TEGDMA in composite eluates. Furthermore, the expression of mitochondrial biogenesis markers and mitochondrial fusion protein, were markedly elevated in TEGDMA rich eluates, especially in VITA-LC group, shown as elongated mitochondrial morphology and aberrant mitochondrial functions. Overall, TEGDMA could elute easier from those resin composites with less filler content and cause oxidative stress in HGFs via mitochondria dysregulation. These data can be instructive to optimize the synthesis of resin composites from the perspective of biocompatibility. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1132-1142, 2019.

Cytotoxicity of one-step dentin-bonding agents toward dental pulp and odontoblast-like cells.

The purpose of this study was to compare the cytotoxicity of five one-step dentin-bonding agents on human dental pulp and odontoblast-like cells (MDPC-23). Photopolymerized and unpolymerized samples of these dentin-bonding agents were prepared and incubated with dental pulp or MDPC-23 cells. After 24 or 72 h of incubation, the number of unstained cells with trypan blue was counted. The staining of cells with trypan blue stands for a cytotoxicity. The pulp cell and MDPC-23 cytotoxicity of polymerized sample treatment increased in the order of AQ Bond Plus (AQ)

A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse.

AIM: To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse. DESIGN, SETTING AND PARTICIPANTS: A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU). INTERVENTION: Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits. OUTCOME: Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide

Histological biocompatibility of new, non-absorbable glaucoma deep sclerectomy implant.

We performed this study to compare the intrascleral biocompatibility of three materials: non-absorbable hydrogel contact lens polymer, non-absorbable silicone rubber, and absorbable cross-linked sodium hyaluronate. Intrascleral implantation of three different materials was performed in 13 healthy, pigmented rabbits. Implants of methacrylic hydrogel, silicone rubber, and cross-linked sodium hyaluronate were implanted in 10, 8, and 8 eyes, respectively. The animals were euthanized at 7, 30, 180, and 360 days post implantation. The eyes were enucleated and immediately fixed in 10% buffered formalin. Semithin sections were cut and stained with hematoxylin-eosin. Light microscope analysis of the specimens was performed. The least severe inflammatory reaction was observed with cross-linked sodium hyaluronate implants. The number of inflammatory cells in proximity to methacrylic hydrogel and silicone implants at all periods of follow up was similar. The thickest fibrous capsule was observed with silicone implants (average, 28.38 +/- 11.17 microm). This area was thinner with methacrylic hydrogel implants (average, 14.90 +/- 5.57 microm) and was thinnest around sodium hyaluronate implants (average, 7.21 +/- 2.33 microm). For each type of implant, the wall on the conjunctival side of the fibrous capsule was significantly thicker than the wall on the choiroidal side. The space between the implant, scleral flap, and bed was filled soon after surgery with connective tissue rich in vessels. In our study, cross-linked sodium hyaluronate had the highest intrascleral biocompatibility. Although the inflammatory responses of the sclera to methacrylic hydrogel and silicone rubber were similar in nature, a thicker fibrous capsule was generated around silicone implants.

Physicians' counseling of patients when prescribing nicotine replacement therapy.

AIMS: Nicotine patches and gum are now available without a prescription in many countries. Some have expressed concern that allowing access to these medications without a prescription may deprive smokers of the instruction and support they would otherwise have received from their physician. We assessed the value of physician involvement in NRT prescription. DESIGN AND PARTICIPANTS: We analyzed data interviews from 993 subjects who had filled prescriptions for patch (n=669) or gum (n=324) about physician behavior when prescribing patch and gum when these were available only by prescription. FINDINGS: 82% of smokers actually met with the physician; however, only 67% received some instruction in using the medication; only 50% were told about potential side effects; and substantial fractions were prescribed a dose that differed from that recommended on the usage instructions (patch: 24%; gum: 33%). Participants who received no intervention from their physicians were significantly more likely to be abstinent than those participants who received smoking cessation advice and support, likely because physicians offered help to those who most needed it, biasing the association. CONCLUSIONS: These findings suggest that physicians did not typically perform the helpful behaviors often expected of them or attributed to them.

Guinea Pig Maximization Test of tri-ethylene glycol mono-methacrylate.

The aim of this study was to evaluate tri-ethylene glycol mono-methacrylate (TEGMA) in terms of dermatological allergic reaction using a Guinea Pig Maximization Test. Skin reaction was evaluated according to the criteria of International Contact Dermatitis Research Group. TEGMA, as a constituent in new primers, has been reported to contribute to a priming ability similar to that of highly purified glyceryl mono-methacrylate (GM). In this study, it was found that its adverse effect was less than that of 2-hydroxy ethyl methacrylate (2-HEMA), but similar to that of highly purified GM. In conclusion, it was anticipated that TEGMA would hereafter replace 2-HEMA as a primer, as it posed a lower risk of triggering dermatological allergic reaction.

The effects of BIS-GMA and TEG-DMA on female mouse fertility.

OBJECTIVES: The current study evaluated the effect of bisphenol A glycerolate dimethacrylate (BIS-GMA) and triethyleneglycol dimethacrylate (TEG-DMA) on female mouse fertility. METHODS: Adult female mice were exposed to BIS-GMA or TEG-DMA (0, 25 and 100 microg/kg) intragastrically daily for 28 d and then mated with sexually mature untreated male mice and after mating their fertility was assessed. RESULTS: In females exposed to BIS-GMA at both doses significant increases in the total number of resorptions out of the total number of implantations were observed, with a significant increase in the number of animals with resorptions at the higher dose. Significant reductions in body weights and significant increases in ovary weights were also observed. Exposure to TEG-DMA at a dose of 100 microg/kg resulted in significant reductions in pregnancy rates and a significant increase in the total number of embryonal resorptions. Significant reductions in body and uterine weights were also observed in females exposed to TEG-DMA. SIGNIFICANCE: The results suggest that both BIS-GMA and TEG-DMA have reproductive toxic effects in female mice.

Skin penetration and dermal tolerability of acrylic nanocapsules: Influence of the surface charge and a chitosan gel used as vehicle.

For an improved understanding of the relevant particle features for cutaneous use, we studied the effect of the surface charge of acrylic nanocapsules (around 150nm) and the effect of a chitosan gel vehicle on the particle penetration into normal and stripped human skin ex vivo as well as local tolerability (cytotoxicity and irritancy). Rhodamin-tagged nanocapsules penetrated and remained in the stratum corneum. Penetration of cationic nanocapsules exceeded the penetration of anionic nanocapsules. When applied on stripped skin, however, the fluorescence was also recorded in the viable epidermis and dermis. Cationic surface charge and embedding the particles into chitosan gel favored access to deeper skin. Keratinocytes took up the nanocapsules rapidly. Cytotoxicity (viability<80%), following exposure for ≥24h, appears to be due to the surfactant polysorbate 80, used for nanocapsules stabilization. Uptake by fibroblasts was low and no cytotoxicity was observed. No irritant reactions were detected in the HET-CAM test. In conclusion, the surface charge and chitosan vehicle, as well as the skin barrier integrity, influence the skin penetration of acrylic nanocapsules. Particle localization in the intact stratum corneum of normal skin and good tolerability make the nanocapsules candidates for topical use on the skin, provided that the polymer wall allows the release of the active encapsulated substance.

The effect of triethylene glycol dimethacrylate on the cell cycle of mammalian cells.

The induction of DNA damage by a genotoxic agent is a signal leading to cell cycle delay, and thereby enables and induces DNA repair prior to cell cycle progression. Triethylene glycol dimethacrylate (TEGDMA), a monomer of dental resinous materials, caused mutagenic effects in mammalian cells probably as a consequence of DNA damage. Therefore, we hypothesized that TEGDMA will induce a cell cycle delay in mammalian cells. Here, cell lines deficient and proficient of a functional p53 tumor suppressor protein were used to study the effects of TEGDMA on the various phases of the cell cycle. V79 Chinese hamster lung fibroblasts (p53 deficient), N1 human skin fibroblasts (p53 proficient), and primary human pulp fibroblasts (p53 proficient) were exposed to increasing TEGDMA concentrations (0-3 mmol/l). Cell survival and vitality were determined after a 24-h exposure period and a 24-h recovery period, and the distribution of cells between the phases of the cell cycle in untreated and TEGDMA-treated cultures was analyzed by flow cytometry. The majority of the TEGDMA-treated V79 cells accumulated in G2 phase. In contrast, about 30% of human N1 fibroblasts were reversibly blocked in G1 phase by 0.5-3.0 mmol/l TEGDMA. The fraction of G2-phase cells was increased only by high TEGDMA concentrations. The percentage of human pulp cells in G1 phase increased very slightly with 1 mmol/l TEGDMA, but cell numbers in G1 phase were reduced by 10-20% by 1.5-3 mmol/l TEGDMA. The percentage of pulp cells in G2 phase increased about 2-fold without any obvious effect of a 24-h recovery period. Therefore, TEGDMA caused cell cycle delays through p53-dependent and independent pathways in the various cell lines. From these results, we conclude that TEGDMA may influence physiological processes like cell growth and differentiation of human pulp cells in vivo.