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Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis

Paulino, Niraldo; Abreu, Sheila Rago Lemos; Uto, Yoshihiro; Koyama, Daisuke; Nagasawa, Hideko; Hori, Hitoshi; Dirsch, Verena M; Vollmar, Angelika M; Scremin, Amarilis; Bretz, Walter A
Artepillin C is the major compound in the Brazilian green propolis from Baccharis dracunculifolia. Our aim in this study was to investigate the anti-inflammatory effects, absorption, and bioavailability of Artepillin C in mice. The animals used were male Swiss mice subjected to: paw oedema by carrageenan (300 microg/paw), carrageenan-induced peritonitis, and prostaglandin E(2) determination. We also measured in vitro nitric oxide production by RAW 264.7 cells and NF-kappaB activity in HEK 293 cells. Finally, we measured the absorption and bioavailability of Artepillin C in plasma from mice by means of GC-MS after a single oral dose (10 mg/kg). In vivo, Artepillin C produced a maximal inhibition of 38% after 360 min on paw oedema. Artepillin C also decreased the number of neutrophils during peritonitis (IC(50): 0.9 (0.5-1.4) mg/kg). Treatment with Artepillin C decreased prostaglandin E(2) by 29+/-3% and 58+/-5% at 1 and 10 mg/kg, respectively, with a mean ID(50) of 8.5 (8.0-8.7) mg/kg). Similarly, in in vitro models, Artepillin C (3, 10, or 100 microM) decreased nitric oxide production by RAW 264.7 cells with a mean IC(50) of 8.5 (7.8-9.2) microM. In HEK 293 cells, Artepillin C reduced NF-kappaB activity with a mean IC(50) of 26 (22-30) mug/ml), suggesting anti-inflammatory activity, particularly during acute inflammation. Lastly, Artepillin C was absorbed after an oral dose (10 mg/kg) with maximal peaks found at 1 h (22 microg/ml). Collectively, Artepillin C showed anti-inflammatory effects mediated, at least in part, by prostaglandin E(2) and nitric oxide inhibition through NF-kappaB modulation, and exhibited bioavailability by oral administration
PMID: 18474366
ISSN: 0014-2999
CID: 153336

Inheritance of occlusal topography: a twin study

Su, C-Y; Corby, P M; Elliot, M A; Studen-Pavlovich, D A; Ranalli, D N; Rosa, B; Wessel, J; Schork, N J; Hart, T C; Bretz, W A
AIM: This was to determine the relative contribution of genetic factors on the morphology of occlusal surfaces of mandibular primary first molars by employing the twin study model. METHODS: The occlusal morphology of mandibular primary first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12 dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three-dimensional (3D) scanner. To compare the similarity of occlusal morphology between twin sets, each twin pair of occlusal surfaces was superimposed to establish the best fit by using computerized least squared techniques. Heritability was computed using a variance component model, adjusted for age and gender. RESULTS: DZ pairs demonstrated a greater degree of occlusal morphology variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018 (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24) sample and were not statistically significant (p=0.2203). The transformed mean differences were not statistically significantly different (p=0.2203). Heritability estimates of occlusal surface areas for right and left mandibular primary first molars were 97.5% and 98.2% (p<0.0001), respectively. CONCLUSIONS: Occlusal morphology of DZ twin pairs was more variable than that of MZ twin pairs. Heritability estimates revealed that genetic factors strongly influence occlusal morphology of mandibular primary first molars
PMCID:3142568
PMID: 18328234
ISSN: 1818-6300
CID: 153335

[[Streptococcus mutans Acquisition and Dental Caries Development in First-Born Children].]

Noce, Erica; Rubira, Cassia Maria Fischer; da Silva Rosa, Odila Pereira; da Silva, Salete Moura Bonifacio; Bretz, Walter Antonio
OBJECTIVE: To evaluate the moment of streptococcus mutans (SM) acquisition, caries development and their associate variables along 23 months, in first-born children of low socioeconomic status families, starting at 7 months of age. METHOD: The sample was chosen based on highly SM-colonized mothers, including all members of 14 families living in the same houses. The study included 14 mothers, 14 fathers and 14 first-borns and 8 relatives (mostly grandparents). Initial clinical examinations and radiographs determined the caries indices and periodontal conditions of the adults. SM count in all adults was made in the first 2 visits. The children were examined for SM count, number of teeth and number of carious lesions, in 4 visits. RESULTS: SM prevalence was high in the adults, being absent in only one of the parents. SM was found in 1, 2, 3 and 10 children in the first, second, third and fourth visits. Dental caries was detected in only 3 children in the last visit (at 30 months), who presented significantly higher SM scores than the children without caries in the same visit. CONCLUSION: A low income social condition and mothers highly colonized by SM do not mean necessarily early SM colonization and high caries activity in children with oral homecare. Caries development is significantly associated with high SM scores in the children.
PMCID:3183577
PMID: 22022218
ISSN: 1519-0501
CID: 178157

Chlorhexidine does not provide a significant effect on the control of coronal and root caries development in the elderly

Bretz, Walter A
PMID: 18155079
ISSN: 1532-3390
CID: 153129

Heritability of oral microbial species in caries-active and caries-free twins

Corby, Patricia M; Bretz, Walter A; Hart, Thomas C; Schork, Nicholas J; Wessel, J; Lyons-Weiler, James; Paster, Bruce J
Oral microbes that colonize in the mouths of humans contribute to disease susceptibility, but it is unclear if host genetic factors mediate colonization. We therefore tested the hypothesis that the levels at which oral microbes colonize in the mouth are heritable. Dental plaque biofilms were sampled from intact tooth surfaces of 118 caries-free twins. An additional 86 caries-active twins were sampled for plaque from carious lesions and intact tooth surfaces. Using a reverse capture checkerboard assay the relative abundance of 82 bacterial species was determined. An integrative computational predictive model determined microbial abundance patterns of microbial species in caries-free twins as compared to caries-active twins. Heritability estimates were calculated for the relative microbial abundance levels of the microbial species in both groups. The levels of 10 species were significantly different in healthy individuals than in caries-active individuals, including, A. defectiva, S. parasanguinis, S. mitis/oralis, S. sanguinis, S. cristatus, S. salivarius, Streptococcus sp. clone CH016, G. morbillorum and G. haemolysans. Moderate to high heritability estimates were found for these species (h(2) = 56%-80%, p < .0001). Similarity of the overall oral microbial flora was also evident in caries-free twins from multivariate distance matrix regression analysis. It appears that genetic and/or familial factors significantly contribute to the colonization of oral beneficial species in twins
PMCID:3148892
PMID: 18179393
ISSN: 1832-4274
CID: 153334

Child neglect and oral health problems in offspring of substance-abusing fathers

Mezzich, Ada C; Bretz, Walter A; Day, Bang-Shiuh; Corby, Patricia M; Kirisci, Levent; Swaney, Michelle; Cornelius, Jack R; Weyant, Robert J
This study examined (1) orodental (OD) problems in 10-19-year-old children of substance use disorder (SUD) (n = 127) and non-SUD fathers (n = 111) and (2) the moderating effect of child's substance use (SU) involvement in the associations of paternal SUD and neglectful parenting with OD problems in the offspring. The results showed that periodontal problems differentiated between groups and the interactions between child's SU involvement and paternal SUD and neglectful parenting were respectively associated with hard/soft tissue lesions and carious lesions in the offspring, indicating that SU involvement increases risk for OD due to paternal SUD and neglectful parenting
PMID: 17882611
ISSN: 1055-0496
CID: 153332

Oral indicators of eating disorders are more readily detected by female than male dentists

Bretz, Walter A
PMID: 17599662
ISSN: 1532-3390
CID: 153136

Benefits of additional courses of systemic azithromycin in periodontal disease case report

Schmidt, Edgard F; Bretz, Walter A
The strong association of subgingival anaerobic bacteria, such as Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, with destructive periodontal disease has been well documented in the literature. Several double-blind studies have also shown the beneficial use of systemic antimicrobials that are active against these microorganisms in conjunction with conventional periodontal treatment, especially when periodontal abscesses and/or suppuration upon probing are present. Four cases with periodontal abscesses were treated with scaling/root planing in conjunction with systemic azithromycin. Partial improvement led to retreatment with two additional courses of azithromycin. Bone formation was noted on periapical radiographs after the patients took additional courses of azithromycin. In view of the benefits of using additional courses of azithromycin in the treatment of destructive periodontal disease, we conclude that the single course of systemic antimicrobials currently used in periodontal therapy may be insufficient to reach necessary therapeutic levels in infected sites
PMID: 17891880
ISSN: 0028-7571
CID: 153333

Microbial acid production (Clinpro Cario L-Pop) and dental caries in infants and children

Bretz, W A; Corby, P M A; Costa, S; Quadros, M; Tavares, V S; Moreira, G; Filho, M R Melo; Weyant, R J
OBJECTIVE: The purpose of this study was to evaluate the diagnostic utility of the Clinpro Cario-L-Pop test as it relates to dental caries rates and severity in infants and children. METHOD AND MATERIALS: The study population was comprised of 771 infants and children who were on average 5.2 years of age (range of 1.5 to 8 years of age). Examiners conducted dental caries clinical examination using established criteria. In addition, lesion severity was determined be measuring its depth. An indicator swab was applied to the tongue dorsum until completely moistened with saliva. The indicator swab was processed according to the manufacturer's instructions, and acid production was assessed with the aid of a color chart. RESULTS: Twenty-three percent of children were caries free, and 7% (n = 50) of participants were categorized as having low production of lactic acid (scores 1 to 3), 17% (n = 135) moderate production of lactic acid (scores 4 to 6), and 76% (n = 586) high production of lactic acid (scores 7 to 9). There was a tendency for moderate and high lactic acid formers to exhibit higher surface-based caries prevalence rates, higher rates for deep dentinal lesions, and increased lesion severity. There was a linear increase of white spot surface-based lesions from low to high lactic acid formers and for initial dentinal lesions. Clinpro Cario-L-Pop test results, when controlling for age and gender, significantly distinguished caries-free participants from those exhibiting any form of decay. CONCLUSION: These results suggest that Clinpro Cario-L-Pop test was useful in explaining elevated frequency and severity of dental caries in spite of the high levels of decay and of microbial acid production observed in this population
PMCID:3151418
PMID: 17530054
ISSN: 0033-6572
CID: 153331

Heritability estimates for dental caries and sucrose sweetness preference

Bretz, Walter A; Corby, Patricia M A; Melo, Mario R; Coelho, Mania Q; Costa, Simone M; Robinson, Miguel; Schork, Nicholas J; Drewnowski, Adam; Hart, Thomas C
OBJECTIVE: The aim of this study was to determine heritability estimates for dental caries traits and sucrose sweetness preference. DESIGN: Participants included 115 pairs of twins 4-7-years-old. Caries exams followed NIDCR criteria where the severity of the lesion was also determined. Twins ranked their preference for five concentrations of sucrose/grape juice solutions (0.15-1.17M) with a Face Scale. Variables submitted to analysis: (1) surface-based caries prevalence rate (SBCPR); (2) lesion severity index (LSI); (3) sucrose sweetness preference score (SSPS). Heritability analyses were performed with the SOLAR software package. RESULTS: Heritability estimates adjusted for age and gender were: SBCPR-h(2)=64.6 (p<.00001), LSI-h(2)=61.7 (p<.00001) and SSPS-h(2)=55.2 (p<.00001). Treating SPSS as a covariate in the SBCPR and LSI models did not alter heritability estimates. CONCLUSIONS: These results suggest that variation in dental caries traits and sucrose sweetness preference have a significant genetic contribution that is mediated independently
PMID: 16934741
ISSN: 0003-9969
CID: 152631