Neuroimaging biomarkers of glial activation for predicting the annual cognitive function decline in patients with Alzheimer's disease.

BACKGROUND: Glial activation is central to the pathogenesis of Alzheimer's disease (AD). However, researchers have not demonstrated its relationship to longitudinal cognitive deterioration. We aimed to compare the prognostic effects of baseline positron emission tomography (PET) imaging of glial activation and amyloid/tau pathology on the successive annual cognitive decline in patients with AD. METHODS: We selected 17 patients diagnosed with mild cognitive impairment or AD. We assessed the annual changes in global cognition and memory. Furthermore, we assessed the predictive effects of baseline amyloid and tau pathology indicated by cerebrospinal fluid (CSF) concentrations and PET imaging of glial activation (11C-DPA-713-binding potential in the area of Braak 1-3 [11C-DPA-713-BPND]) on global cognition and memory using a stepwise regression analysis. RESULTS: The final multiple regression model of annual changes in global cognition and memory scores included 11C-DPA-713-BPND as the predictor. The CSF Aß42/40 ratios and p-tau concentrations were removed from the final model. In stepwise Bayesian regression analysis, the Bayes factor-based model comparison suggested that the best model included 11C-DPA-713-BPND as the predictor of decline in global cognition and memory. CONCLUSIONS: Translocator protein-PET imaging of glial activation is a stronger predictor of AD clinical progression than the amount of amyloid/tau pathology measured using CSF concentrations. Glial activation is the primary cause of tau-induced neuronal toxicity and cognitive deterioration, thereby highlighting the potential of blocking maladaptive microglial responses as a therapeutic strategy for AD treatment.

Involvement of inflammation in the medial temporal region in the development of agitation in Alzheimer's disease: an in vivo positron emission tomography study.

BACKGROUND: The evaluation of 11 C-DPA-713 binding using positron emission tomography for quantifying the translocator protein can be a sensitive approach in determining the level of glial activation induced by neuroinflammation. Herein, we aimed to investigate the relationship between regional 11 C-DPA713-binding potential (BPND ) and neuropsychiatric symptoms (NPS) in amyloid-positive Alzheimer's disease (AD) patients. METHODS: Fifteen AD patients were enrolled in this study. Correlations were evaluated between the 11 C-DPA713-BPND and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores, including scores in its four domains: agitation, psychosis, affective, and apathy. 11 C-DPA713-BPND values were compared between groups with and without the neuropsychiatric symptoms for which a relationship was observed in the abovementioned correlation analysis. RESULTS: A positive correlation was found between the severity of agitation and 11 C-DPA713-BPND in the Braak 1-3 area, including the amygdala, hippocampal and parahippocampal regions, and lingual and fusiform areas. An increase in the 11 C-DPA713-BPND was observed in AD patients with agitation. We did not find any significant effects of possible confounding factors, such as age, duration of illness, education, gender, Mini-Mental State Examination score, cerebrospinal fluid amyloid ß 42/40 ratio, and apolipoprotein E4 positivity, on either the 11 C-DPA713-BPND or agitation score. CONCLUSIONS: Neuroinflammation in the medial temporal region and its neighbouring area was shown to be associated with the development of agitation symptoms in AD patients. Our findings extend those of previous studies showing an association between some NPS and inflammation, suggesting that immunologically based interventions for agitation can serve as an alternative treatment for dementia.

Estimation of blood-based biomarkers of glial activation related to neuroinflammation.

Background: Neuroinflammation is a well-known feature of Alzheimer's disease (AD), and a blood-based test for estimating the levels of neuroinflammation would be expected. In this study, we examined and validated a model using blood-based biomarkers to predict the level of glial activation due to neuroinflammation, as estimated by 11C-DPA-713 positron emission tomography (PET) imaging. Methods: We included 15 patients with AD and 10 cognitively normal (CN) subjects. Stepwise backward deletion multiple regression analysis was used to determine the predictors of the TSPO-binding potential (BPND) estimated by PET imaging. The independent variables were age, sex, diagnosis, apolipoprotein E4 positivity, body mass index and the serum concentration of blood-based biomarkers, including monocyte chemotactic protein 1 (MCP-1), fractalkine, chitinase 3-like protein-1 (CHI3L1), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and clusterin. Results: Sex, diagnosis, and serum concentrations of MCP1 and sTREM2 were determined as predictors of TSPO-BPND in the Braak1-3 area. The serum concentrations of MCP1 and sTREM2 correlated positively with TSPO-BPND. In a leave one out (LOO) cross-validation (CV) analysis, the model gave a LOO CV R2 of 0.424, which indicated that this model can account for approximately 42.4% of the variance of brain TSPO-BPND. Conclusions: We found that the model including serum MCP-1 and sTREM2 concentration and covariates of sex and diagnosis was the best for predicting brain TSPO-BPND. The detection of neuroinflammation in AD patients by blood-based biomarkers should be a sensitive and useful tool for making an early diagnosis and monitoring disease progression and treatment effectiveness.

Season of birth and vulnerability to the pathology of Alzheimer's disease: an in vivo positron emission tomography study.

BACKGROUND: This study used positron emission tomography to examine whether the seasonal birth effect as an exogenic indicator of early life environmental factors influenced vulnerability to Alzheimer's disease (AD) pathology in the elderly. METHODS: We analysed datasets from the Alzheimer's Disease Neuroimaging Initiative, which included the data for 234 cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) (n = 114) and AD dementia (n = 38). As an index of amyloid ß (Aß)/tau accumulation, the 18 F-AV-45- and 18 F-AV-1451-standardized uptake value ratios (SUVRs) were compared between groups of spring-to-summer births and fall-to-winter births by analysis of covariance. In addition, a multiple linear regression analysis was performed to determine whether the season of birth was a predictor of 18 F-AV-45 and/or 18 F-AV-1451 SUVRs, for which a difference was observed. RESULTS: Seasonal birth difference was a good predictor of 18 F-AV-1451 SUVR. We found that participants with a fall-to-winter birth showed lower 18 F-AV-1451 SUVRs than those with a spring-to-summer birth in both the CN and MCI/AD groups, after correcting for the effect of age, sex, years of education, and Alzheimer's Disease Assessment Scale cognitive subscale score, that could possibly affect tau accumulation. CONCLUSIONS: Participants with a fall-to-winter birth showed less tau accumulation than those with a spring-to-summer birth after accounting for the factors that could affect tau accumulation. Our findings showed a vulnerability to tau pathology in participants with a fall-to-winter birth, which may be caused by perinatal or postnatal brain damage due to the risk factors associated with the cold season.

Kinetic modeling and non-invasive approach for translocator protein quantification with 11C-DPA-713.

INTRODUCTION: 11C-DPA-713 is a positron emission tomography (PET) radiotracer developed for imaging the expression of the translocator protein (TSPO) in glial cells, which is considered to be a marker of the neuroinflammatory burden. This study investigated the pharmacokinetic profile of 11C-DPA-713 and evaluated kinetic modeling and non-invasive TSPO quantification using dynamic PET imaging data in the Alzheimer's disease (AD) and cognitive normal (CN) participants. METHODS: Eleven patients with AD and 6 CN participants were examined using dynamic 11C-DPA-713 PET imaging for 60 min with arterial blood sampling. Time-activity curves were calculated from the cerebellum and three composite regions of interest (ROIs), according to the anatomical definitions of Braak's stages 1 to 3, stage 4, stage 5, and stage 6 that correspond to the pathological stages of tangle deposition. The total distribution volume (VT) was evaluated using compartmental modeling and graphical analysis. Reference region-based methods were implemented using an optimal area that was assumed to be void of the radiotracer target as reference tissue. RESULTS: The concentration of radioactivity in plasma demonstrated rapid clearance. 11C-DPA-713 peaked rapidly in the gray matter. Compartmental modeling resulted in a good fit, and the one-tissue model with estimated blood volume correction (1Tv) showed the best performance. The estimated VT obtained from the graphical plasma methods was highly correlated with that obtained from 1Tv. Reference region-based analysis was conducted using the Braak 6 area as the reference region, and the estimated non-displaceable binding potential was highly correlated with that obtained from 1Tv. CONCLUSION: 11C-DPA-713 possesses properties suitable for TSPO quantification with PET imaging. The Braak 6 area was shown to be a useful reference region in the patients with AD and the CN participants, and non-invasive reference tissue models using the Braak 6 area as a reference region can be employed for TSPO quantification with 11C-DPA-713-PET imaging as an alternative to the invasive compartmental model.

Comparison of dimension reduction methods on fatty acids food source study.

Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.

Evaluation of the effects of three pretreatment conditioners and a surface preparation system on the bonding durability of composite resin adhesive to a gold alloy.

This study aimed to evaluate the effect of three pretreatment conditioners and surface preparations on a composite resin adhesive for a gold alloy. Cast disk specimens were made and bonded with RelyX Unicem luting agent under six surface conditions: 1) polished with No.600 carbide paper, 2) air-abraded with alumina, 3) Alloy Primer metal conditioner was applied after alumina-abrasion, 4) Monobond Plus multipurpose conditioner was applied after alumina-abrasion, 5) M. L. Primer metal conditioner was applied after alumina-abrasion, and 6) Rocatec multipurpose silica-coating system was applied. The bond strengths were determined before and after thermocycling (50,000 cycles). The bond strengths of the alumina-abrasion group were significantly decreased after thermocycling. The Rocatec and M. L. Primer exhibited higher bond strengths than other treatments. The application of metal conditioners and multipurpose surface preparations was recommended for improved bonding between the evaluated adhesive resin and gold alloy.

Significant effects of cholinesterase inhibitors on tau pathology in the Alzheimer's disease continuum: An in vivo positron emission tomography study.

OBJECTIVES: No prior study has assessed the effects of cholinesterase inhibitors (ChEIs) on tau pathology in the brains of patients with Alzheimer's disease (AD). Using positron emission tomography, this study aimed to investigate whether ChEIs reduce tau aggregation in amyloid-positive participants. METHODS: We analyzed datasets from the Alzheimer's Disease Neuroimaging Initiative and included amyloid-positive participants who had undergone baseline and 1- or 2-year follow-up AV-1451 positron emission tomography scans. We included participants treated with and without ChEIs (ChEIs group: n = 15, No-ChEIs group, n = 45). The annual change in tau aggregation was calculated as the difference in AV-1451- standardized uptake value ratio (SUVR) between the two scans divided by the time between scans. Group differences in annual AV-1451-SUVR change were examined. RESULTS: We found a significantly lower annual change in AV-1451-SUVR in the Braak 1/2 regions (entorhinal cortex and hippocampus) of participants taking ChEIs. Increased AV-1451-SUVR between the first and second examinations were observed in 22 of 45 participants not taking ChEIs and 2 of 15 participants taking ChEIs. Fisher's exact test showed a significant difference in the ratio of participants with increased AV-1451-SUVR between the groups. CONCLUSIONS: The findings of this positron emission tomography study suggest that the administration of ChEIs has some neuroprotective effects in patients of the AD continuum, at least in the early stage of the disease progression. This in vivo effect may be mediated via tau, preventing amyloid ß-induced neurotoxicity.

Strongyloides stercoralis colitis in a patient positive for human T-cell leukaemia virus with rheumatoid arthritis during an anti-rheumatic therapy: a case report.

An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhoea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukaemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing S. stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.

Relationship between neuropsychiatric symptoms and Alzheimer's disease pathology: An in vivo positron emission tomography study.

OBJECTIVES: To investigate the relationship between amyloid-ß- and tau-based Alzheimer's disease (AD) pathologies assessed using positron emission tomography imaging and neuropsychiatric symptoms (NPS) in a sample of AD continuum including clinically normal subjects and patients with mild cognitive impairment or AD. METHODS: We analyzed datasets of the Alzheimer's disease Neuroimaging Initiative and included amyloid-positive subjects who underwent an AV-45 scan within 1 year of an AV-1451 scan (n = 99). Correlation between standardized uptake value ratio (SUVR) of AV-45 and AV-1451 and the Neuropsychiatric Inventory (NPI) score (and its four domain subscores for hyperactivity, psychosis, affective, and apathy) was evaluated. Stepwise logistic regression analysis was used to examine the influence of SUVRs on the presence of NPS. SUVRs were also tested for their ability to discriminate the group with NPS using receiver operating characteristic (ROC) curve analyses. RESULTS: Significant positive relationships were found between the total NPI score and affective symptoms and Braak 1&2 (transentorhinal region) AV-1451 SUVR. Stepwise logistic regression analysis identified tau accumulation in the area of Braak 1&2 as a significant covariate discriminating the presence of affective symptoms. The area under the ROC curve analysis showed that subjects with affective symptoms were discriminated by AV-1451 SUVR with an accuracy of 77.7%. CONCLUSIONS: Tau aggregation in the transentorhinal region, where neurodegeneration affected by tau pathology was seen in the early stage of AD, correlated with more severe NPS, especially affective symptoms. Therefore, tau pathology in the transentorhinal cortex might be associated with affective symptoms in the early stage of AD.

Interaction effect of Alzheimer's disease pathology and education, occupation, and socioeconomic status as a proxy for cognitive reserve on cognitive performance: in vivo positron emission tomography study.

AIM: Educational attainment, occupation, and socioeconomic status have been regarded as major factors influencing cognitive reserve (CR). This study aimed to investigate the interaction effect of amyloid-ß/tau burden and education/occupation/socioeconomic status as a proxy for CR on cognitive performance. METHODS: We analyzed the datasets of the Alzheimer's Disease Neuroimaging Initiative. We included clinically normal subjects and patients with mild cognitive impairment or Alzheimer's disease who had undergone a florbetapir scan within 1 year of a flortaucipir (AV-1451) scan (n = 127). Partial correlation analysis between the standardized uptake value ratio of florbetapir/AV-1451 and the proxy for CR was performed with the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) score as a covariate. Stepwise multiple linear regression analysis was performed to determine the predictors of ADAS-cog performance based on the interaction between the imaging biomarkers and the proxy for CR. RESULTS: We found a significant positive partial correlation between educational level and tau pathology in Braak stage 1/2 areas, and we observed significantly higher tau accumulation among participants with higher education when ADAS-cog score was used as a covariate. The interaction between tau and education was a good predictor of cognitive function, with higher tau accumulation showing a greater association with higher ADAS-cog score among participants with less education than among those with more education. CONCLUSION: Our findings indicate the protective effect of education against cognitive dysfunction in early-stage Alzheimer's disease pathology and suggest that education may exert a beneficial effect by reducing the adverse cognitive consequences of tau aggregation.

Multivariate Analysis for Molecular Species of Cholesteryl Ester in the Human Serum.

Cholesteryl ester (CE) is an ester of cholesterol and fatty acid (FA). Plasma CE reflects complicated metabolisms of cholesterol, phospholipids, lipoproteins, and dietary FAs. An informatics approach could be useful for analysis of the CE species. In this study, two basic dimension reduction methods, principal component analysis (PCA) and factor analysis, were applied to serum CE species determined by LC-MS/MS in a Japanese population (n = 545). PCA and factor analysis both reflected the size (concentration), food source, fat solubility, and biological aspect of the CE species. In a comparison between PCA (PC4) and factor analysis (factor 4), the latter was found to be more suggestive from a biological aspect of n-6 FAs. Cholesteryl docosahexaenoate (DHA) was found to be unique by a factor analysis, possibly relevant to the unique accumulation of DHA in the brain. An informatics approach, especially factor analysis, might be useful for the analysis of complicated metabolism of CE species in the serum.

Effects of polymerization method on flexural and shear bond strengths of a fiber-reinforced composite resin.

This study investigated the effects of indirect composite polymerization on the postcuring mechanical properties of a fiber-reinforced composite. An indirect composite seated on glass fibers preimpregnated with polymerized monomer was polymerized by 1) photoirradiation using a halogen-fluorescent polymerizing unit for 5 min, 2) method 1 plus secondary heating at 100°C for 15 min, 3) photoirradiation using a metal halide light unit for 60 s, or 4) preliminary polymerization using a halogen light unit for 20 s followed by method 3. After polymerization, the flexural and shear bond strengths of the fiber-reinforced composite were examined, as was the flexural strength of non-fiber-reinforced composite specimens polymerized using the same methods. Among non-fiber-reinforced composite specimens, flexural strength was lower for method 1 than for the other three methods; however, among fiberreinforced composite specimens, the four methods did not significantly differ in flexural strength or shear bond strength. Composite-fiber interface separation without breakage of the fiber after flexural strength testing was not observed in specimens polymerized by methods 2 or 4. In conclusion, use of a conventional unit for high-intensity light irradiation after preliminary irradiation, or light irradiation followed by secondary heating, is recommended for polymerization of composite material seated on polymerized glass fiber.

Bonding durability between acrylic resin adhesives and titanium with surface preparations.

The purpose of the present study was to evaluate the efficacy of pretreatment on the bonding durability between titanium casting and two acrylic adhesives. Cast titanium disk specimens treated with four polymer-metal bonding systems as follow: 1) air-abraded with 50-70 µm alumina, 2) 1)+Alloy Primer, 3) 1)+M.L. Primer and 4) tribochemical silica/silane coating system (Rocatec System). The specimens were bonded with M bond or Super-bond C&B adhesive. The shear bond strengths were determined before and after thermocycling (20,000 cycles). The surface characteristics after polishing, and for the 1) and 4) preparations were determined. The bond strengths for all combinations significantly decreased after thermocycling. The combination of Super-bond C&B adhesive and 2) led to significantly higher bond strength than the other preparations after thermocycling. The maximum height of the profile parameters for the polishing group was lower than other preparations.

Effect of metal conditioner on bonding of porcelain to cobalt-chromium alloy.

PURPOSE: The purpose of this study was to evaluate the efficacy of two different metal conditioners for non-precious metal alloys for the bonding of porcelain to a cobalt-chromium (Co-Cr) alloy. MATERIALS AND METHODS: Disk-shaped specimens (2.5×10.0 mm) were cast with Co-Cr alloy and used as adherend materials. The bonding surfaces were polished with a 600-grid silicon carbide paper and airborne-particle abraded using 110 µm alumina particles. Bonding specimens were fabricated by applying and firing either of the metal conditioners on the airborne-particle abraded surface, followed by firing porcelain into 5 mm in diameter and 3 mm in height. Specimens without metal conditioner were also fabricated. Shear bond strength for each group (n=8) were measured and compared (α=.05). Sectional view of bonding interface was observed by SEM. EDS analysis was performed to determine the chemical elements of metal conditioners and to determine the failure modes after shear test. RESULTS: There were significant differences among three groups, and two metal conditioner-applied groups showed significantly higher values compared to the non-metal conditioner group. The SEM observation of the sectional view at bonding interface revealed loose contact at porcelain-alloy surface for non-metal conditioner group, however, close contact at both alloy-metal conditioner and metal conditioner-porcelain interfaces for both metal conditioner-applied groups. All the specimens showed mixed failures. EDS analysis showed that one metal conditioner was Si-based material, and another was Ti-based material. Si-based metal conditioner showed higher bond strengths compared to the Ti-based metal conditioner, but exhibited more porous failure surface failure. CONCLUSION: Based on the results of this study, it can be stated that the application of metal conditioner is recommended for the bonding of porcelain to cobalt-chromium alloys.

Evaluation of fracture resistance of indirect composite resin crowns by cyclic impact test: influence of crown and abutment materials.

This study evaluated the effect of abutment materials on the fracture resistance of composite crowns for premolars. Composite crowns were fabricated using two different indirect composite resin materials (Meta Color Prime Art or Estenia C&B) and cemented onto either a metal (Castwell M.C. 12) or composite resin (Build-It FR and FibreKor) abutment with resin cement (Panavia F2.0). Twenty-four specimens were fabricated for four groups (n=6 each) and subjected to 280-N cyclic impact loading at 1.0 Hz. The number of cycles which caused the composite crown to fracture was defined as its fracture resistance. All data were statistically analyzed using ANOVA and the Bonferroni test (α=0.05). Composite crowns cemented onto resin abutments showed higher fracture resistance than those cemented onto metal abutments.

Influence of light irradiation on Vickers hardness of dual-cure cement polymerized under restorations.

This study evaluated, by measuring Vickers hardness (Hv), the effects of these factors on the degree of polymerization of dual-cure cement (Panavia F2.0) placed under a restoration: light transmission property of restoratives materials, distance from the directly irradiated surface, and elapsed time after light irradiation. Two materials were used for the restoration: silver-palladium-copper-gold alloy (Alloy) versus zirconia (ZR). Restorations were cemented on bovine enamel by dual-cure cement. At 30 min, 2 h, 6 h, 1 day, and 1 week after definitive irradiation, Hv values at the enamel side of cement were evaluated at three measuring points: two points at the left and right margins and one point at the center. Data were analyzed by two-way ANOVA with Bonferroni correction (α=0.05). With the Alloy restoration, Hv value at the center was significantly lower than those at the margins at 30 min after irradiation. For both Alloy and ZR restorations, Hv value at each measuring point continued to increase significantly up to 6 h.

Effect of adherend temperature on bond strengths of resin bonding systems to denture base resin and a semi-precious alloy.

This study investigated the effect of adherend temperature on shear bond strengths of auto-polymerizing resin to denture base resin and 4-META/MMA-TBBO resin to silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy. Bonding procedure was carried out when adherend temperature was 10, 23, 37, or 55°C, and shear bond strengths (SBSs) were measured before and after thermocycling. Before thermocycling, there were no significant differences in bond strength among the four adherend temperatures for each adhesive resin: 31.59±6.11-32.89±2.12 MPa for auto-polymerizing resin; 35.43±2.2-38.38±0.61 MPa for 4-META/MMA-TBBO resin. After thermocycling, optimal adherend temperature to achieve the highest bond strength was 37°C for auto-polymerizing resin to denture base resin (30.02±2.29 MPa) and 10ºC for 4-META/MMA-TBBO resin to Ag-Pd-Cu-Au alloy (37.14±2.17 MPa).

History and current state of metal adhesion systems used in prosthesis fabrication and placement.

The adhesion techniques used in prosthetic dentistry have substantially improved with respect to retention of veneering resin to the metal framework of resin-veneered restorations and the bonding of resin-bonded fixed partial dentures (RBFPDs) to abutment teeth. In the early 1970s, prostheses relied on macromechanical retention for veneering surfaces and the retention holes of retainers. Later, retention was achieved by using small spherical particles. In addition, the use of small pits created by electrochemical corrosion was tested in resin-veneered restorations and RBFPDs. Thus, micromechanical retention gradually supplanted macromechanical retention. First-generation adhesive monomers were introduced at the end of the 1970s and were succeeded in the early 1980s by the marketing of adhesive resin cements, which were effective for use with non-noble alloys when surface oxidation procedures were used. In 1994, a second-generation adhesive primer for noble alloys was introduced, which prompted development of other adhesive primers. These primers were applied mainly to silver-palladium-copper-gold and type IV gold alloys and improved the reliability of RBFPDs. Recent studies have confirmed the effectiveness of such primers when used with high-gold-content metal ceramic alloys. Due to these developments, RBFPDs now have excellent esthetic characteristics.

Effect of adhesion promoting monomer addition to MMA-TBBO resin on bonding to pure palladium.

This study evaluated the effects of combined use of metal primers and modified monomers on the bonding of MMA-TBBO resins to pure palladium (Pd). Bonding surface was polished with 600-grit silicon carbide paper and primed with one of these four metal primers: V-Primer, M. L. Primer, Metaltite, or Alloy Primer. Four monomers, including three modified ones, were added to MMATBBO resin. One was a methyl methacrylate monomer containing no adhesion promoting monomers, while the other two modified monomers contained the functional monomer of either V-Primer or Alloy Primer. Bonded specimens were prepared by incremental build-up of MMA-TBBO resin on primed Pd surfaces. Shear bond strengths were measured after thermal cycling. Bonding to Pd was significantly improved when modified monomer containing the functional monomer of Alloy Primer was used in combination with M. L. Primer or Metaltite applied on the bonding surface.