Masking of High-Translucency Zirconia for Various Cores.

CLINICAL RELEVANCE: Various core materials with different shades affect the final color of high-translucency monolithic zirconia restorations. The blue core shows the greatest color difference in final zirconia restorations followed by metal, A3 dentin-shade resin core, and white core. SUMMARY: The purpose of this study was to evaluate the masking ability of high-translucency monolithic zirconia for various core materials. A computer-aided design-computer-aided manufacturing system was used to design a zirconia disc with a diameter of 10 mm and a thickness of 1.0 mm. Four groups of cores (n=15 each) were fabricated with blue-colored dual-cure resin, white-colored dual-cure resin, A3 dentin-shade composite resin, and titanium block with 10-mm diameter and 5-mm thickness.Dual-cure, self-adhesive resin cement discs with a thickness of 25.0 ± 0.02 µm were fabricated. The color was measured using a handheld spectrophotometer. Color measurements of all specimens were performed on a white background. To assess the masking ability of zirconia, the difference between the values measured with zirconia on a white background and the values measured with zirconia on each of the four types of core material as a background with the cement specimens interposed (zirconia + cement + core) was determined. To enhance the optical connection between the specimens, distilled water was applied between each layer during each measurement.The results showed that the value of ΔE was highest for the blue core followed by metal, A3 dentin-shade resin core, and white-resin core. No significant differences were observed between the metal core and the A3 dentin-shade resin core or between the A3 dentin-shade resin core and the white core. The blue core had the significantly highest ΔE value based on Tukey's honest significant difference test.Different core materials affect the final color of high-translucency monolithic zirconia restorations. Thus, our study showed that the final color of high-translucency monolithic zirconia restorations could be affected by the type of core material used.

Effect of Insufficient Light Exposure on Polymerization Kinetics of Conventional and Self-adhesive Dual-cure Resin Cements.

OBJECTIVES: The purpose of this study was to investigate the influence of insufficient light exposure on the polymerization of conventional and self-adhesive dual-cure resin cements under ceramic restorations. METHODS: Two conventional dual-cure resin cements (Rely-X ARC, Duolink) and two self-adhesive resin cements (Rely-X U200, Maxcem Elite) were polymerized under different curing modes (dual-cure or self-cure), curing times (20 and 120 seconds), and thickness of a ceramic overlay (2 and 4 mm). Polymerization kinetics was measured by Fourier transform infrared spectroscopy for the initial 10 minutes and after 24 hours. Data were analyzed using mixed model analysis of variance (ANOVA), one-way ANOVA/Student-Newman-Keuls post hoc test, and paired t-test (α=0.05). RESULTS: When light-curing time was set to 20 seconds, the presence of the ceramic block significantly affected the degree of conversion (DC) of all resin cements. Especially, the DC of the groups with 20 seconds of light-curing time under 4 mm of ceramic thickness was even lower than that of the self-cured groups at 24 hours after polymerization (p<0.05). However, when light-curing time was set to 120 seconds, a similar DC compared with the group with direct light exposure (p>0.05) was achieved in all dual-cure groups except Maxcem Elite, at 24 hours after polymerization. CONCLUSIONS: For both conventional and self-adhesive dual-cure resin cements, insufficient light exposure (20 seconds of light-curing time) through thick ceramic restoration (4 mm thick) resulted in a DC even lower than that of self-curing alone.

Implication of European-derived adiposity loci in African Americans.

OBJECTIVE: Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. METHODS: A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. RESULTS: Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005

Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort.

OBJECTIVE: Previous studies have replicated the association of variants within FTO (fat mass- and obesity-associated) intron 1 with obesity and adiposity quantitative traits in populations of European ancestry. Non-European populations, however, have not been so intensively studied. The goal of this investigation was to examine the association of FTO single-nucleotide polymorphisms (SNPs), prominent in the literature in a multiethnic sample of non-Hispanic White American (n=458), Hispanic American (n=373) and African American (n=288) subjects from the Insulin Resistance Atherosclerosis Study (IRAS). This cohort provides the unique ability to evaluate how variation within FTO influences measures of adiposity and glucose homeostasis in three different ethnicities, which were ascertained and examined using a common protocol. DESIGN: A total of 26 FTO SNPs were genotyped, including those consistently associated in the literature (rs9939609, rs8050136, rs1121980, rs1421085, rs17817449 and rs3751812), and tested for association with adiposity and glucose homeostasis traits. RESULTS: For the adiposity phenotypes, these and other SNPs were associated with body mass index (BMI) in both non-Hispanic Whites (P-values ranging from 0.015 to 0.048) and Hispanic Americans (P-values ranging from 7.1 × 10(-6) to 0.027). In Hispanic Americans, four other SNPs (rs8047395, rs10852521, rs8057044 and rs8044769) still showed evidence of association after multiple comparisons adjustment (P-values ranging from 5.0 × 10(-5) to 5.2 × 10(-4)). The historically associated BMI SNPs were not associated in the African Americans, but rs1108102 was associated with BMI (P-value of 5.4 × 10(-4)) after accounting for multiple comparisons. For glucose homeostasis traits, associations were seen with acute insulin response in non-Hispanic Whites and African Americans. However, all associations with glucose homeostasis measures were no longer significant after adjusting for multiple comparisons. CONCLUSION: These results replicate the association of FTO intron 1 variants with BMI in non-Hispanic Whites and Hispanic Americans but show little evidence of association in African Americans, suggesting that the effect of FTO variants on adiposity phenotypes shows genetic heterogeneity dependent on ethnicity.

Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1.

Human chromosome 20q12-q13.1 has been linked to type 2 diabetes mellitus (T2DM) in multiple studies. We screened a 5.795-Mb region for diabetes-related susceptibility genes in a Caucasian cohort of 310 controls and 300 cases with T2DM and end-stage renal disease (ESRD), testing 390 SNPs for association with T2DM-ESRD. The most significant SNPs were found in the perigenic regions: HNF4A (hepatocyte nuclear factor 4alpha), SLC12A5 (potassium-chloride cotransporter member 5), CDH22 (cadherin-like 22), ELMO2 (engulfment and cell motility 2), SLC13A3 (sodium-dependent dicarboxylate transporter member 3), and PREX1 (phosphatidylinositol 3,4,5-triphosphate-dependent RAC exchanger 1). Haplotype analysis found six haplotype blocks globally associated with disease (p<0.05). We replicated the PREX1 SNP association in an independent case-control T2DM population and inferred replication of CDH22, ELMO2, SLC13A3, SLC12A5, and PREX1 using in silico perigenic analysis of two T2DM Genome-Wide Association Study data sets. We found substantial heterogeneity between study results.

Buccal bone plate thickness of the Asian people.

Distances from the apex to the buccal bone plate were measured on the computed tomography (CT) images of 1806 teeth from 66 patients, using an image analyzer program (Image-Pro Plus, Ver. 4.0, Media Cybernetics). In the mandible, the mean distance from the distal apex of the mandibular second molar to the buccal bone plate was the largest distance measured, at 8.51 mm, followed by distance from the mesial root to the buccal bone (7.34 mm). In the mandibular first molar, the mean distal and mesial bone thicknesses were 5.18 mm and 4.09 mm, respectively. However, when there were two distal roots, the distance of the disto-lingual root to the buccal plate was found to be 9.52 mm, which constitutes the greatest measured thickness. In the maxillary buccal roots, the distances from the mesio-buccal and disto-buccal root of the second molar to the buccal bone plate were the largest, at 4.63 mm and 3.61 mm, respectively. The average distances from the palatal apex of the maxillary first and second molars to the buccal bone plate were 10.69 mm and 10.17 mm, respectively, while, from the palatal bone plate, average distances of 3.15 mm and 3.08 mm were measured. Special considerations, such as bony lid approach, lingual approach, or intentional replantation may be required, especially when a patient has a surgical need in the second molars and the disto-lingual root of the mandibular first molar, or in the palatal root of the maxillary molars.

Genetic analysis of nitric oxide and endothelin in end-stage renal disease.

BACKGROUND: Genetic factors have been implicated in the development of the common aetiologies of end-stage renal disease (ESRD), including renal failure attributed to hypertension, diabetes mellitus, systemic lupus erythematosus and human immunodeficiency virus infection. Nitric oxide (NO) and endothelin are powerful vasoactive mediators involved in inflammation and regulation of vascular tone and blood pressure. We evaluated the role of the neuronal constitutive (NOS1) and endothelial constitutive (NOS3) nitric oxide synthase genes and the endothelin-1 (EDN-1) gene in predisposition to chronic renal failure in African-Americans. METHODS: The study population for the linkage and association analyses in ESRD consisted of 361 individuals from 168 multiplex African-American families. These individuals comprised 207 unweighted sibling pairs concordant for all-cause ESRD. Microsatellite markers NOS1B (NOS1), D7S636 (NOS3) and CPHD1-1/2 (EDN-1) were genotyped in the sample. In addition, a mutation, Glu298Asp, in exon 7 of NOS3 and a 27 bp variable number tandem repeat (VNTR) marker in intron 4 of NOS3 were evaluated in the sibling pairs and in an additional 92 unrelated African-Americans with type 2 diabetes mellitus-associated ESRD (singletons). Association analyses utilized the relative predispositional effect method. Model independent linkage analyses were performed using GeneHunter-plus and MapMaker/SIBS (exclusion analysis) software. RESULTS: Significant evidence for association with ESRD was detected for alleles 7 and 9 of the NOS1 gene (11.9 and 34.2%, respectively, in unrelated probands of ESRD families versus 6.5 and 27.5%, respectively, in race-matched controls, both P:<0.01). These associations were maintained when the unrelated first sibling from each family was used in a case-control comparison and was most pronounced in the non-diabetic ESRD cases. The NOS3 and EDN-1 markers failed to provide consistent evidence for association in the sibling pairs and the diabetic ESRD singletons, although we identified two novel endothelial constitutive NOS4 (ecNOS4) VNTR alleles in African-Americans. Significant evidence for linkage was not detected between the NOS genes or the EDN-1 gene in either all-cause ESRD or when the ESRD sibling pairs were stratified by aetiology (type 2 diabetic ESRD or non-diabetic aetiologies). CONCLUSION: Based upon the consistent allelic associations, we believe that further evaluation of the NOS1 gene in ESRD susceptibility in African-Americans is warranted.

Malignant papillary neoplasms of the intrahepatic bile ducts: CT and histopathologic features.

OBJECTIVE. We describe the CT and pathologic features of malignant papillary neoplasms of the intrahepatic bile ducts in 15 patients. CONCLUSION. CT is a useful technique for revealing intraductal lesions, although the findings are nonspecific and variable. When intraductal masses or nodules are seen with localized dilatation of the intrahepatic bile ducts on CT scans, malignant papillary neoplasms of the intrahepatic bile ducts should be included in the differential diagnosis.

Molecular epidemiology and association of putative pathogens in root canal infection.

The purpose of this study was to investigate the epidemiology of putative pathogens in root canals with apical periodontitis and to determine the associations among the putative pathogens. Eighteen symptomatic and 20 asymptomatic teeth from 36 subjects were studied. This research was performed with polymerase chain reaction and hybridization using rRNA-based oligonucleotide probes. The most frequently found species was Fusobacterium sp. (68.4%), followed by Peptostreptococcus micros (44.7%) and Porphyromonas gingivalis (26.3%). Sixteen teeth (42.1%) contained one or more species of the selected black-pigmented bacteria. Bacteroides forsythus and Treponema sp. were detected in 8 teeth and 6 teeth, respectively. Among the analyzed bacteria, significant relationships were shown in the combination of B. forsythus/P. gingivalis and Treponema sp./P. gingivalis. There was no significant association between any bacteria and any symptoms.

Evaluation of markers on human chromosome 10, including the homologue of the rodent Rf-1 gene, for linkage to ESRD in black patients.

There is abundant evidence supporting the contribution of genetic factors to the development of end-stage renal disease (ESRD) in blacks. Two renal failure susceptibility genes, Rf-1 and Rf-2, have been identified in the fawn-hooded rat, an animal model of hypertension and nephrosclerosis. The human homologous region containing the rodent Rf-1 gene has been localized to chromosome 10q. We tested for genetic linkage between 21 polymorphic markers on human chromosome 10 and chronic renal failure in 129 black sibling pairs concordant for ESRD. Two adjacent markers on 10p, D10S1435 and D10S249 (4 centiMorgans from D10S1435), approached significance for linkage to ESRD in sibling pairs with nondiabetic causes of ESRD (P = 0.035 pairwise, P = 0.082 multipoint for D10S1435; P = 0.074 pairwise, P = 0.063 multipoint for D10S249). The markers spanning the homologous region of Rf-1 did not show evidence for linkage to ESRD in sibling pairs concordant for diabetic ESRD, sibling pairs concordant for nondiabetic causes of ESRD, or in the entire family set. These results suggest that the human homologue of Rf-1 is unlikely to contribute substantially to renal failure susceptibility from the common causes of kidney disease in blacks.

Renal angiomyolipoma: selective arterial embolization--effectiveness and changes in angiomyogenic components in long-term follow-up.

PURPOSE: To evaluate the efficacy of selective arterial embolization in symptomatic renal angiomyolipoma (AML) and the change in angiomyogenic components during long-term follow-up after embolization. MATERIALS AND METHODS: Fourteen adult patients with symptomatic AMLs underwent 16 selective arterial embolizations. The embolic materials used were absolute alcohol with (n = 5) or without (n = 3) iodized oil, Gianturco coils (n = 4), and polyvinyl alcohol foam powder with gelatin sponge (n = 2). Follow-up ultrasonography and computed tomography (CT) were performed in six and 14 patients, respectively. The effectiveness of selective arterial embolization was evaluated on the basis of the area of the angiomyogenic components in the AML on initial and follow-up images and clinical improvement. RESULTS: All patients showed devascularization of the tumor on the postembolization angiograms. In 13 patients, clinical symptoms disappeared. The follow-up period was 7-72 months (mean, 33 months). One patient underwent nephrectomy at 7 months after embolization because of a large cystic lesion found at 1 month. In long-term CT follow-up (> or =12 months) in 12 patients, nearly all angiomyogenic components disappeared, but fatty components partially shrank with liquefactive necrosis in tumors. CONCLUSION: Selective arterial embolization is an effective and safe treatment of AML. The angiomyomatous components crucial for the prevention of bleeding were very sensitive to the embolization.

Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus.

PCR primers specific to the human liver fructose-1,6-bisphosphatase (FBP) gene were designed and used to isolate a cosmid clone. Physical mapping of the FBP cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC = 0.35), located the liver FBP gene to chromosome 9q22.3 with no recombination between FBP and the index markers D9S196 (Zmax = 13.2), D9S280 (Zmax = 11.7), D9S287 (Zmax = 15.6), and D9S176 (Zmax = 14.4). Amplification using FBP exon-specific primers with a YAC contig from this region of chromosome 9 further refined the placement of FBP genomic sequences to an approximately 1.7-cM region flanked by D9S280 and D9S287, near the gene for Fanconi anemia group C. Precise localization of the FBP gene enabled evaluation of FBP as a candidate gene for maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes (NIDDM) in both Caucasian and African-American families, using the highly informative markers D9S287 and D9S176. Although FBP is a rate-limiting enzyme in gluconeogenesis, using both parametric and nonparametric analysis there was no evidence for linkage of FBP to diabetes in these families.

Enzyme-linked immunosorbent assay and enzyme-linked coagulation assay for detection of Clostridium botulinum neurotoxins A, B, and E and solution-phase complexes with dual-label antibodies.

The measurement of toxins A, B, and E from Clostridium botulinum was accomplished by use of a modified sandwich enzyme-linked immunosorbent assay (ELISA) employing labeled horse antibody and either chicken antibody or biotinylated horse antibody. The complexes formed in solution phase were captured onto solid phases coated with rabbit anti-chicken immunoglobulin G (chicken antibody) or avidin (biotinylated antibody). The assay was brought to the sensitivity of the mouse bioassay (5 to 10 pg/ml, or 0.03 to 0.07 pM) by employing as labeling enzyme the factor X activator of Russell's viper venom (RVV-XA) and a sensitive coagulation-based assay amplification system known as enzyme-linked coagulation assay. Complex formation was found to be a slower reaction than binding to the capture plate, and so the assay used a preincubation step to produce the solution-phase complexes before they were bound to the solid phase. Keeping the concentrations of Russell's viper venom factor X activator antibody and capture antibody constant for diluted samples and diluting complexes into buffer without keeping labeled antibody concentrations constant were equivalent in allowing the detection of low neurotoxin concentrations. This ELISA-enzyme-linked coagulation assay procedure is a convenient alternative to the mouse bioassay, which shows complete resolution of the neurotoxins in addition to the requisite sensitivity.

Immunoaffinity chromatographic purification of Russell's viper venom factor X activator using elution in high concentrations of magnesium chloride.

RVV-X, the factor X activator from Russell's viper venom, has been isolated using affinity chromatography on agarose columns of a monoclonal antibody specific for this enzyme. Upon testing acid, alkaline, and high concentrations of MgCl2 for elution, it was found that use of high concentrations of MgCl2 was most effective in elution of RVV-X. It was nondenaturing and yielded 90% recovery of homogeneous enzyme without measurable contamination by other proteins of the venom.

Sensitive enzyme-linked immunosorbent assay for detection of Clostridium botulinum neurotoxins A, B, and E using signal amplification via enzyme-linked coagulation assay.

A new immunoassay amplification method has been applied to the measurement of toxins A, B, and E from Clostridium botulinum. The technique is a modified enzyme-linked immunosorbent assay (ELISA) which relies on the detection of sandwich complexes on microtiter plates by a solid-phase coagulation assay known as ELCA, or enzyme-linked coagulation assay. In the method, a coagulation activating enzyme (RVV-XA) isolated from the venom of Russell's viper is conjugated to affinity-purified horse antibodies specific for toxin type A, B, or E. Plates are coated with affinity-purified antibodies, and standard captag (capture-tag) protocols using labeled antibody are employed to bind the toxin from solution. Complexes are detected by adding a modified plasma substrate which contains all the coagulation factors mixed with alkaline phosphatase-labeled fibrinogen and solid-phase fibrinogen; deposition of solid-phase, enzyme-labeled fibrin on the solid phase is then a reflection of formation of toxin-RVV-XA-antibody complexes on the solid phase. Because of the ability to detect RVV-XA by this coagulation assay at concentrations < 0.1 pg/ml, it was possible to measure C. botulinum toxins A, B, and E at mouse bioassay levels (< 10 pg/ml, or < 0.07 pM) for both purified neurotoxin and crude culture filtrates obtained from strains known to produce appropriate single toxins. ELISA-ELCA should be applicable to measurement of toxins in most of the materials (contaminated food, blood, and excreta) for which the comparably sensitive mouse bioassay is currently employed. This method has the potential of broad application to the measurement of low concentrations of any antigen for which appropriate immunochemical reagents are available, in a color test format.

Disulfiram and erythrocyte aldehyde dehydrogenase inhibition.

During disulfiram therapy erythrocyte aldehyde dehydrogenase (ALDH) was fully inhibited. The time for total loss of erythrocyte ALDH activity ranged from 36 to 120 hr. In contrast to the 85% recovery of in vitro disulfiram-inhibited ALDH activity, this in vivo disulfiram-ALDH inhibition could not be reversed by mercaptoethanol. It is proposed that the in vivo and in vitro mechanisms of ALDH inhibition by disulfiram differ. Erythrocyte ALDH activity can be readily monitored to determine patient compliance and is an accessible model for investigations of in vivo mechanisms of drug inhibition. Because the disulfiram-inhibited erythrocyte ALDH is not regenerated until new erythrocytes are made (120 days), a significant portion of the extrahepatic acetaldehyde metabolic capacity remains inhibited for long periods after disulfiram is discontinued. Thus, the recidivistic patient who discontinues disulfiram and waits several days (to regenerate liver ALDH activity) before drinking will be exposed to even higher ethanol-derived blood acetaldehyde levels than usual, which may induce further alcohol-associated organ damage and alcohol dependence.

Clinical comparison of propoxyphene napsylate and methadone in the treatment of opiate dependence.

In this double-blind comparison of propoxyphene napsylate (PN) 800 mg in two divided doses versus methadone 20 mg, methadone 10 mg or placebo methadone, it was found that PN: 1) did not alleviate withdrawal symptoms in patients previously maintained on methadone 20 mg; 2) produced a slightly overmedicated effect in the detoxified group of exmethadone patients; and 3) compared favorably to methadone 10 mg in suppressing withdrawal symptoms without producing evidence of overmedication in those patients previously stabilized on a methadone maintenance dose of 10 mg.

Initial methadone dose in treating opiate addiction.

Intramuscular administration of naloxone was used to precipitate the narcotic withdrawal syndrome in opiate-dependent patients. Objective signs of withdrawal were rated according to a previously developed scale. Based upon naloxone-induced withdrawal scores, 76 patients were given a dose of methadone, either low, medium, or high, in a randomized double-blind manner on 2 consecutive days. The adequacy of the methadone dose was evaluated by assessing the patients' physical responses after each treatment. Results indicate that the medium dose of methadone in each naloxone-induced withdrawal score range provides optimal control of narcotic deprivation. It is concluded that a correct initial dose of methadone can be administered when the degree of opiate dependence is established by the naloxone test.