A Prospective Longitudinal Study of Early Childhood Caries Onset in Initially Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex oral disease that is prevalent in US children. OBJECTIVES: The purpose of this 2-y prospective cohort study was to examine baseline and time-dependent risk factors for ECC onset in initially caries-free preschool children. METHODS: A cohort of 189 initially caries-free children aged 1 to 3 y was recruited. At each 6-mo study visit, children were examined using the ICDAS index; salivary samples were collected to assess mutans streptococci (MS), lactobacilli, Candida species, salivary cortisol (prior and after a stressor), and salivary IgA. Diet and oral health behavior were assessed from parent report. Child and family stress exposure was assessed from measures of psychological symptoms, stressful life event exposure, family organization and violence exposure, and social support. Sociodemographic factors were also considered. A Kaplan-Meier estimator of survival function of time to ECC and a Cox proportional hazards model were used to identify predictors of ECC onset. RESULTS: Onset of ECC was associated with high salivary MS levels at baseline (log-rank test, P < 0.0001). Cox proportional hazards regression showed that the risk of dental caries significantly increased with salivary MS in log scale over the 6-mo period (hazard ratio, 1.08; P = 0.01). Other risk factors in the model did not reach statistical significance. CONCLUSION: Our results provide prospective evidence that an increase in salivary MS predicts ECC onset in young, initially caries-free children, confirming that a high salivary MS count likely plays a causal role in ECC onset, independent of covariates. KNOWLEDGE TRANSFER STATEMENT: These results suggest that we must focus on reducing salivary MS counts in young children and preventing or delaying MS colonization in infants and young children determined to be at risk for ECC.

Social, Psychological, and Behavioral Predictors of Salivary Bacteria, Yeast in Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex, multifactorial oral disease that is a major public health concern because it is prevalent, profoundly alters a child's quality of life, is difficult to treat effectively, and has a distressing tendency to recur following treatment. OBJECTIVES: The purpose of the study was to examine social, psychological, and behavioral predictors of salivary bacteria and yeast in young children at risk for ECC. METHODS: A sample of 189 initially caries-free preschool children was assessed for child stress physiology from salivary cortisol, child and family stress exposure, diet, oral health behaviors, and sociodemographic risks. Multiple logistic regression analysis was implemented to examine the associations between these risk factors and cariogenic microorganisms: mutans streptococci (MS), lactobacilli (LB), and Candida species. RESULTS: Higher baseline salivary cortisol (odds ratio [OR] = 6.26; 95% confidence level [CL], 1.69-23.16) and a blunted response to an acute laboratory stressor (OR = .56; 95% CL, .37-.83) were associated with an increased likelihood of elevated salivary MS (≥105 colony-forming units/mL) in caries-free children. Sociodemographic risk for cariogenic microorganisms was also found. Specifically, lower education attainment of the parent/primary caregiver was associated with children being more likely to carry salivary Candida species and elevated salivary MS; in addition, children from households with an unemployed parent/primary caregiver were more likely (OR = 3.13; 95% CL, 1.2-8.05) to carry salivary Candida species and more likely (OR = 3.03; 95% CL, 1.25-7.33) to carry elevated levels of MS and/or salivary Candida and/or LB. CONCLUSIONS: The impact of sociodemographic risk and stress physiology on cariogenic disease processes are evident prior to ECC onset. The findings provide novel data on the early onset of cariogenic processes in children and the importance of considering sociodemographic, psychosocial, and behavioral factors when judging ECC risk. KNOWLEDGE TRANSFER STATEMENT: The findings provide valuable and novel findings that, pre-ECC onset, the caries disease process is explicable from a detailed assessment of behavioral, sociodemographic, and psychosocial stress variables.

Removable Denture Wearing as a Risk Predictor for Pneumonia Incidence and Time to Event in Older Adults.

INTRODUCTION: Older adults are more susceptible to a common respiratory infection: pneumonia. Nearly 1 million older adults per year are hospitalized for community-acquired pneumonia in the United States. OBJECTIVE: To examine whether wearing removable dentures are associated with an increased risk of pneumonia incidence in a geriatric population. METHODS: We conducted a retrospective cohort study among patients >65 y of age within a large academic health system (University of Rochester Medical Center). The medical and dental electronic records from 2010 to 2018 were reviewed and used for data collection. The exposure was removable denture wearing. The main outcome variables were the incidence of pneumonia and time to event of pneumonia. A Cox proportional hazards regression was used to examine the association between pneumonia onset and wearing removable dentures, adjusting for demographics, socioeconomic status, and medical and dental conditions. RESULTS: A total of 2,364 patients were included, with 1,189 (50.29%) in the denture-wearing group and 1,175 (49.70%) in the non-denture wearing group. The annual pneumonia incidence rate per 100,000 persons was 1,191 in the denture-wearing group and 128 per 100,000 persons in the non-denture wearing group, with a crude incidence rate ratio of 9.33 (95% CI, 5.41 to 18.81; P < 0.0001). The mean ± SD age of the pneumonia onset was 78.0 ± 10.0 and 78.6 ± 9.0 y among denture-wearing and nonwearing groups (P = 0.84). The time to event of pneumonia was associated with removable denture wearing (yes/no; hazard ratio, 7.68 [95% CI, 3.91 to 15.08]; P < 0.001) after adjusting for covariates. CONCLUSIONS: Wearing removable dentures was found to be a risk predictor for pneumonia incidence among the geriatric population even after accounting for other risk factors. KNOWLEDGE TRANSFER STATEMENT: Wearing removable dentures was found to be a risk predictor of pneumonia incidence among older adults. Although the current study does not imply a causal relationship between denture wearing and pneumonia, clinicians and older patients could reference the study results when choosing dental prostheses to restore missing teeth.

Development of a prognostic model for caries onset and progression from early childhood caries incidence in urban preschool children.

AIM: Of this prospective cohort study was to assess early childhood caries (ECC) incidence and, based on the data, build a model that not only predicts future ECC onset in clinically caries-free children, but also is prognostic for children with ECC. METHODS: ECC incidence was assessed at the 12-month follow-up examination on a cohort of 291 preschool children. Weighted general estimation equation (WGEE) was used to estimate the effects of covariates on ds (decayed primary tooth surfaces) and dfs (decayed and filled primary tooth surfaces). RESULTS: The mean dfs at the baseline examination was 0.81. Of the 116 children who completed the study, approximately 22% examined at baseline had ECC (dfs > 0). At 12-months, 36% had ECC with a mean dfs of 2.22. Children with dfs = 0 at baseline had 2.95 fewer ds in the primary dentition at the end of the study than children who had ECC at the baseline examination (dfs > 0) (p < 0.0001). Children with dfs = 0 at baseline had 5.49 fewer ds and dfs in the primary dentition at the end of the study than children who had ECC at the baseline examination (dfs > 0) (p < 0.0001). CONCLUSIONS: ECC incidence at 1 year was 14%. The prevalence of ECC at the 12-month follow-up examination was approximately 36%. The model developed from these data strongly indicate that past caries experience in the primary dentition is a significant predictor of future caries activity and severity, as well as a predictor of future caries onset in clinically caries-free children.

Oral Bacterial Acid-Base Metabolism in Caries Screening: A Proof-Of-Concept Study.

The objective of this cross-sectional study was to clinically validate an array of biochemical tests for oral acid/alkali generation as caries screening instruments. 185 adult subjects (mean 33.6±10.6 years) were examined clinically for dental caries using the ICDAS criteria. Bitewing radiographs were used to confirm interproximal surfaces of posterior teeth. For the purposes of this study, subjects were classified as "caries-active" if they had at least one untreated caries lesion with ICDAS 4 or higher. Pooled supragingival plaque and unstimulated saliva samples were collected and assayed for pH changes from sucrose and urea metabolism using colorimetric tests. The validity of each test to discriminate between "caries-inactive" and "caries-active" subjects was assessed and compared to a commercial bacteriological caries-screening test using roc regression and logistic regression models. The AUCs of the plaque-urea (PU: 0.59 (0.51, 0.67)), plaque-urea-glucose (PUG: 0.59 (0.51, 0.67)) and saliva-urea-glucose (SUG: 0.59 (0.51, 0.67)) tests did not differ significantly from the bacteriological tests (CRT-mutans: 0.62 (0.54, 0.70); CRT-lactobacillus: 0.63 (0.56, 0.71) (P>0.05), but the plaque-glucose (SG), saliva-glucose (SG), saliva-urea (SU) and saliva-plaque-glucose (SPG) tests had significantly smaller AUCs (P<0.05). The AUCs for the PU, PUG, SUG, and the CRT-mutans tests were higher in subjects who had no existing dental restorations (PU: 0.90 (0.77, 1.04); PUG: 0.90 (0.79, 1.01); SUG: 0.89 (0.69, 1.08); CRT-mutans: 0.90 (0.73, 1.08)). The incorporation of the biochemical tests into a multidimensional bacteriological/psychosocial caries screening model significantly increased its diagnostic values (Se+Sp: 160.6, AUC: 0.846). In conclusion, as a proof of concept, the results of this study indicate that measuring the ability of dental plaque and saliva to metabolize urea together with the ability to generate acid from sugars may have a promising role in caries screening either independently, or as part of a multidimensional biological test.

New EPCAM founder deletion in Polish population.

It is well known that founder mutations associated with cancer risk have useful implications for molecular diagnostics. We report the presence of a founder mutation in EPCAM involved in the etiology of Lynch syndrome (LS). The mutation extends nearly 8.7 kb (c.858 + 2478_*4507del) and is shared by 8 Polish families. Family members suffered almost exclusively from colorectal cancer; however, pancreatic and gastric cancers were also apparent. Next to mutations c. 2041G>A in MLH1 gene and c.942+3A>T in MSH2, the deletion mutation encompassing EPCAM is one of the most common causative changes responsible for LS in Poland.

Urease activity as a risk factor for caries development in children during a three-year study period: a survival analysis approach.

UNLABELLED: Recent cross-sectional studies suggest that reduced ability to generate alkali via the urease pathway in dental plaque may be an important caries risk factor, but it has not been assessed prospectively. OBJECTIVE: To evaluate the effect of plaque and saliva urease activity on the risk for developing new caries over a three-year period in children. METHODS: A panel of 80 children, three to six years of age at recruitment, was followed prospectively for three years. Plaque urease activity, saliva urease activity and dental caries were measured every six months. Survival analysis methodology was used to evaluate the effect of urease on caries development during the study period adjusted for gender, age, baseline caries levels, sugar consumption, amount of plaque, and mutans streptococci levels. RESULTS: The risk for developing new caries increased in a dose-responsive manner with increasing levels of urease activity in saliva (adjusted HR(Q4 vs. Q1): 4.98; 95% CI: 1.33, 18.69) and with decreasing urease activity in plaque (adjusted HR(Q4 vs. Q1): 0.29; 95% CI: 0.11, 0.76). Multiple measurements of urease activity were conducted to overcome the variability of urease activity in this study. Baseline caries and mutans streptococci in saliva were also important predictors of caries risk. CONCLUSIONS: Increased urease activity in saliva can be an indicator of increased caries risk in children, whilst increased urease activity in plaque may be associated with reduced caries risk. The reproducibility of urease measurements must be improved before these findings can be further tested and clinically applied.

Prevalence of dental caries and dental care utilisation in preschool urban children enrolled in a comparative-effectiveness study.

AIM: To assess dental caries prevalence and dental care utilisation in pre-school children enrolled in urban childcare centres that participated in a comparative effectiveness study. STUDY DESIGN: Cross-sectional study. METHODS: Caries prevalence was determined in a cohort of children 12-60 months of age. Eligible children were randomised into two groups: group one received a traditional visual/tactile oral examination and group two received a teledentistry examination. Questionnaires were administered to the children's parents/guardians to gather demographics and information about using dental and medical services. RESULTS: Of 234 children examined, approximately 28% had caries experience. The mean dfs score was 1.56 with a range of 0-34 carious surfaces. The mean dfs score for the children examined by means of teledentistry was 1.75 and for the children examined by means of the traditional visual/tactile method mean dfs was 1.40; the means between the two groups were not significantly different. Twenty-six children showed evidence of being treated for dental caries. According to the parents, 31.5% of the children had never had a dental check-up before, only 3% of the children were lacking dental insurance and majority of the parents (92%) did not perceive accessing dental care for the children as a problem. STATISTICS: The Wilcoxon Mann-Whitney test and the Kruskal-Wallis test were used to assess statistical differences among groups of children. CONCLUSIONS: The data showed that 28% of the children had caries and, of these, 61% had never been treated for caries, thus indicating that continued efforts are needed to improve oral health care utilisation by inner-city preschool children.

Urease activity in dental plaque and saliva of children during a three-year study period and its relationship with other caries risk factors.

UNLABELLED: Bacterial urease activity in dental plaque and in saliva generates ammonia, which can increase the plaque pH and can protect acid-sensitive oral bacteria. Recent cross-sectional studies suggest that reduced ability to generate ammonia from urea in dental plaque can be an important caries risk factor. In spite of this proposed important clinical role, there is currently no information available regarding important clinical aspects of oral ureolysis in children. OBJECTIVE: The objective of this study was to evaluate the distribution and pattern of urease activity in the dental plaque and in the saliva of children during a three-year period, and to examine the relationship of urease with some important caries risk factors. METHODS: A longitudinal study was conducted with repeated measures over a three-year period on a panel of 80 children, aged 3-6 years at recruitment. The dynamics of change in urease activity were described and associated with clinical, biological, and behavioural caries risk factors. RESULTS: Urease activity in plaque showed a trend to remain stable during the study period and was negatively associated with sugar consumption (P<0.05). Urease activity in unstimulated saliva increased with age, and it was positively associated with the levels of mutans streptococci in saliva and with the educational level of the parents (P<0.05). CONCLUSIONS: The results of this study reveal interesting and complex interactions between oral urease activity and some important caries risk factors. Urease activity in saliva could be an indicator of mutans infection in children.

Caries status and overweight in 2- to 18-year-old US children: findings from national surveys.

BACKGROUND: The prevalence of overweight children in the United States continues to increase. OBJECTIVES: To examine the relationship between being overweight and caries in primary and permanent dentition in a nationally representative sample of children. METHODS: Data from the NHANES III (1988-1994) were analyzed using logistic regression and controlling for potential confounders for 10 180 children 2-18 years of age and from the NHANES 1999-2002 for 7568 children 2-18 years of age. RESULTS: For children 2-5 years of age, there was no difference in caries experience among normal weight, at risk for overweight or overweight children for NHANES III and for NHANES 1999-2002. For children 6-11 years of age (NHANES III), at risk for overweight and overweight children were less likely to have caries experience in the primary dentition than normal weight children; overweight children were less likely to have caries experience in the permanent dentition than normal weight children. For children 12-18 years of age (NHANES III), overweight children were less likely to have caries experience in the permanent dentition than normal weight children. For children 6-11 years of age and 12-18 years of age (NHANES 1999-2002), there was no difference in having caries experience among normal, at risk for overweight and overweight children. CONCLUSIONS: The data from NHANES III and NHANES 1999-2002 provide no evidence to suggest that overweight children are at an increased risk for dental caries. Although no differences in caries rates by weight were found in younger children, interestingly results from NHANES III suggest that being overweight may be associated with decreased rates of caries in older children.

Application of nonhomogenous Markov models for analyzing longitudinal caries risk.

OBJECTIVES: Markov modeling is a useful mathematical procedure for calculating probabilities of disease prognosis. Increasingly, Markov models are being applied in medical and health services research and also in social sciences research. The purpose of our study was to use the Markov process to determine time-dependent transition probabilities for caries-free children to convert to a caries-active state and to assess the impact of salivary mutans streptococci (MS) levels on caries status. METHODS: Our analysis was based on data obtained from a 6-year longitudinal study of risk factors associated with caries onset in children. RESULTS: Based on a two-state Markov model, the probability that a caries-free child would convert to a caries-active state during the study ranged between 0.0046 and 0.0471. The highest probability of converting from a caries-free state to a caries-active state was 0.0471 at age 8.5 years. CONCLUSIONS: In addition to standard statistical methods of analyzing longitudinal caries data, Markov models show promise for use in the analysis of caries risk.

Clinical outcomes for early childhood caries: influence of aggressive dental surgery.

PURPOSE: The objective of this study was to assess the relationship between the number of stainless steel crowns (SSCs) placed, number of surfaces at risk (SAR) post dental surgery, and the risk for relapse in patients treated for Early Childhood Caries (ECC). METHODS: The study population consisted of 57 children treated for ECC under general anesthesia, ranging in age from 2.3 to 7.3 years old at the time of entry. Dental surgery utilized an aggressive approach: teeth that had necrotic pulps or were nonrestorable were extracted; decayed primary mandibular incisors that could not be treated by stripping were extracted; primary maxillary incisors with 3 or more carious surfaces were extracted; single-surface lesions of primary molars that did not compromise cusp integrity were restored with intracoronal amalgam restorations; primary maxillary, incisors and canines with smooth-surface lesions affecting 2 or less surfaces were treated with intracoronal composites; primary molars and canines requiring vital pulp therapy were restored with SSCs; primary molars with caries lesions affecting 2 or more surfaces (including smooth-surface, white-spot lesions) were restored with SSCs; primary canines with caries affecting 3 or more surfaces were restored with stainless steel crowns; topical fluoride was applied after all restorative therapy was completed. The cohort was examined for new caries lesions 6 months post dental surgery. Relapse was defined as the presence of new smooth-surface caries lesions as defined by Radike. Comparisons between relapse (R) and nonrelapse (NR) groups, with respect to the number of SSCs placed and the number of SAR, were performed using t tests and Wilcoxon tests. A 0.05 level of significance was employed in all statistical tests. RESULTS: Twenty-one of the 57 (37%) patients relapsed. No statistically significant difference for the number of SSCs placed or SAR existed between the R group (SSCs: mean = 4.57, median = 4 +/- 2.18; SAR: mean = 39.76, median = 40 +/- 13.62) and NR group (SSCs: mean=5.44, median = 5.5 +/- 2.62; SAR: mean = 39.98, median = 39.5 +/- 15.19). CONCLUSIONS: The risk for relapse in children treated for ECC is not associated with the number of SSCs placed or SAR; aggressive dental surgery for ECC does not result in acceptable clinical outcomes.

Clinical outcomes for Early Childhood Caries (ECC): the influence of salivary mutans streptococci levels.

AIM: To assess the relationship between clinical outcomes for children treated for Early Childhood Caries (ECC) and salivary mutans streptococci (MS) levels. STUDY DESIGN AND METHODS: The study cohort consisted of 79 children (42 males, 37 females) treated for ECC, aged from 2.3 to 7.3 years at time of entry. Whole non-stimulated saliva samples were obtained from each subject prior to dental surgery and at 6 mths post dental surgery, by saturating a cotton swab in the saliva pooled in the floor of the mouth. Samples were placed into PBS on ice and processed within 2 hours. Samples were sonicated, serially diluted and plated onto MSB and SBA agar plates, then incubated 48 hours anaerobically; SBA plates were incubated an additional 24 hours aerobically. The MS level in each sample was expressed as a percentage of the total cultivable flora. The cohort was evaluated for new caries lesions at 6 months post dental surgery. Relapse was defined as the presence of new smooth surface caries lesions. STATISTICS: Comparisons between Relapse (R) and Non-Relapse (NR) groups with respect to mutans streptococci levels were performed using Wilcoxon tests. Within group comparisons were performed using Wilcoxon signed-rank tests. RESULTS: 57 children (72%) returned for the 6 months examination and 21 of these subjects (37%) relapsed. No statistically significant difference in median salivary MS levels existed between the R (0.20%) and NR (0.033%) groups at baseline (p=0.647) or at 6 months post dental surgery (R=0.03%; NR=0.01%; p=0.273). A statistically significant difference between baseline and 6 months post dental surgery was noted in the median salivary MS level within the R group (p=0.0007) and within the NR group (P<0.0001). CONCLUSIONS: The relapse rate (37%) was high and rapid for children treated for ECC. Dental surgery resulted in a statistically significant reduction in salivary MS reservoirs for children treated for ECC. However, this did not translate into acceptable clinical outcomes.

Clinical outcomes for Early Childhood Caries (ECC): the influence of health locus of control.

AIM: To assess the relationship between clinical outcomes for children treated for ECC and health locus of control. STUDY DESIGN AND METHODS: The study cohort consisted of 79 children (42 males, 37 females) treated for ECC; age range was 2.3-7.3 years (mean 4.2 years) at the time of entry into the study. A questionnaire [developed by DeVellis et al., 1993] was administered to each child's parent(s) on the day of dental surgery. This questionnaire examined the expectation that healthcare outcomes in children are influenced by one of the following loci of control: Professional, Parent, Child, Media, Fate and Divine. The cohort was evaluated for new caries lesions at 6 months post dental surgery. Relapse was defined as the presence of new smooth surface caries lesions. STATISTICS: For each locus, the scores for the Relapse versus Non-relapse groups (returning patients) and the scores for the returning versus non-returning patients were compared using t-tests. RESULTS: 57 children (72%) returned for follow-up and 21 of these 57 (37%) relapsed. No statistically significant difference for Relapse versus Non-relapse groups was indicated with respect to the scores for any locus parameter (p values ranged from 0.35 to 0.95). Returning parents (N=57) versus non- returning parents (N=22) exhibited statistically significant differences with respect to the Parent, Divine and Fate loci. Returning parents exhibited higher scores on the Parent locus (p=0.0392) and lower scores on the Fate (p=0.0024) and Divine (p=0.0031) loci. CONCLUSION: 1). The relapse rate (37%) was high and rapid for children treated for ECC; 2). no meaningful difference existed between the Relapse versus Non-relapse groups with respect to each health locus of control parameter; 3). parents who returned for follow-up care appeared to have an internal health locus of control while those who did not return had an external locus.

The association of basic proline-rich peptides from human parotid gland secretions with caries experience.

To address whether there are associations between the peptide composition of human parotid saliva and dental decay (caries) experience, we have characterized the peptides from parotid ductal saliva collected from nine adults who have remained free from dental caries (mean age = 59.2; Decayed Missing Filled Surfaces index [DMFS] = 0) and nine individuals who have experienced caries (mean age = 51.2; mean DMFS = 38.4). Ethanol-soluble peptides were size-fractionated on columns of Bio-Gel P-2; the salivary peptides derived from caries-susceptible subjects appeared larger than those found in the saliva of caries-free subjects. Peptides were then resolved into 19 species by cation exchange HPLC. Sequence analysis identified 18 peptides that appear to be proteolytic cleavage products of the basic proline-rich proteins IB-4, IB-5, IB-7, IB-8b, and P-B. The peptides that were more abundant in saliva obtained from the caries-free group differed from those isolated from the caries-susceptible group. The median peptide concentration of one possible precursor protein, IB-7, was found to be higher in saliva collected from caries-free individuals than in that from caries-susceptible individuals. Although differences were found in the phenotypes of proline-rich proteins expressed by these groups of caries-free and caries-susceptible subjects, no statistically significant associations were observed among proline-rich phenotypes and the level of any peptide. Collectively, our results indicate that proteolytic processing of parotid salivary proteins differs among individuals who have remained caries-free and those who have experienced dental decay.

Polynitroxyl albumin plus tempol attenuates liver injury and inflammation after hepatic ischemia and reperfusion.

PNA+Tempol, albumin containing conjugated (polynitroxyl albumin; PNA) and free (4-hydroxyl-2,2,6,6-tetramethyl-piperidinyl-1-oxyl; Tempol) nitroxide may protect against injury caused by reactive oxygen species. Therefore, the actions of PNA+Tempol on liver injury and inflammation induced by hepatic ischemia and reperfusion (I/R) were examined. Rats were subjected to 1 h ischemia followed by 24 h reperfusion in the absence (I/R) or presence of PNA+Tempol (25%; 15 mL/kg, i.v.) (I/R+PNA+Tempol) or human serum albumin (23%; 13.5 mL/kg, i.v.) (I/R+HSA). Test solutions were administered prior to and for 2 h during reperfusion. Sham-operated rats underwent surgery with neither ischemia nor infusion. I/R+PNA+Tempol rats had significantly less liver injury and inflammation than I/R rats. I/R+PNA+Tempol livers exhibited focal lesions whereas I/R livers exhibited global necrosis. Likewise, plasma ALT activity was significantly lower in I/R+PNA+Tempol rats. PNA+Tempol reduced I/R-induced neutrophil accumulation and intercellular adhesion molecule-1 (ICAM-1) expression. HSA did not alter I/R-induced liver injury or inflammation. Sham-operated rats exhibited normal liver morphology and no inflammation. Attenuation of I/R liver injury by PNA+Tempol may be mediated by its effect on inflammation, the major contributor to I/R injury. Reduction of inflammation by PNA+Tempol is most likely due to the antioxidative nature of the nitroxides.

Hepatic inflammatory responses to alphaalpha-cross-linked hemoglobin infusion in rats.

Cross-linked hemoglobin (alphaalpha-Hb) may be a useful red blood cell substitute if it can be administered safely. However, cell-free hemoglobin has inherent properties that may cause oxidant-mediated toxicity. We investigated whether alphaalpha-Hb induces oxidative or inflammatory responses that lead to liver damage. alphaalpha-Hb (0.5 or 1.0 gm/kg) was infused into rats, and indices of liver injury, inflammation, and oxidative stress were examined. Although focal hepatic necrosis was noted at 24 hours, plasma alanine aminotransferase activity was not increased and lesions were resolved by 48 hours. Modest neutrophil accumulation in hepatic vessels, but not sinusoids, occurred at 24 hours. Heme oxygenase-1 (HO-1) protein and activity were induced in a dose- and time-dependent manner, with maximal induction at 24 hours. Plasma tumor necrosis factor-alpha levels were not significantly increased. Additional cytokine- and oxidant-mediated events such as nuclear transcription factor-kappaB activation and nitric oxide synthase induction were not observed. These results suggest that alphaalpha-Hb-derived products such as heme and ferric iron (Fe3+), potent inducers of HO-1, are responsible for increasing HO-1. HO-1 induction may be a protective response by the liver to metabolize excess heme and Fe3+, thereby providing antioxidative products to counter the potentially damaging oxidants produced by Fe3+-catalyzed reactions.

Clinical evaluation of new designs for intraoral fluoride-releasing systems.

PURPOSE: Intraoral fluoride-releasing (IFR) devices provide elevated levels of fluoride in the mouth for extended periods of time. However, retention and protection of the devices have posed major challenges for clinical applications. The objectives of this study were to develop new methods for retaining and protecting IFR devices in the mouth and to assess their effects on salivary fluoride levels and distribution in adolescents. METHODS: Four different IFR systems (combinations of an IFR device and its retainer) were evaluated in four groups of 10 adolescents each, 12-15 years of age, for a period of six months. Each child wore two IFR systems of a given type affixed to the buccal surface of each permanent maxillary first molar. Unstimulated saliva samples were collected at each clinical examination and analyzed for fluoride. RESULTS: A significant increase in salivary fluoride concentration from a baseline mean of 0.07-0.69 microgram/mL was observed on day 14 postinsertion. IFR system retention was 85% after 6 months and, of the systems retained, 100% were functional. CONCLUSIONS: These findings suggest that IFR devices can be successfully protected and retained in the mouth for prolonged periods of time.

Clinical outcomes for nursing caries treated using general anesthesia.

This study did follow-up examinations of 84 Medicaid-eligible children with nursing caries after they received treatment for nursing caries utilizing general anesthesia. Results at six months suggest that parents are unresponsive to follow-up care and over half of the children seen had new smooth surface caries lesions. While results are preliminary, they suggest that major changes are needed in the tertiary care of children with nursing caries.

Protein tyrosine kinase activity regulates nitric oxide synthase induction in rat hepatocytes.

Regulation of induced nitric oxide synthase (NOS) in isolated rat hepatocytes is poorly understood. The specific protein tyrosine kinase inhibitor genistein was used to determine if NOS induction is dependent on protein tyrosine kinase activation. Genistein inhibited tumor necrosis factor-alpha (TNF-alpha)-stimulated induction of NOS activity and NOS protein in a dose-dependent manner. Genistein also impaired TNF-alpha-induced NOS mRNA accumulation, suggesting protein tyrosine kinase regulation of NOS induction occurred at the level of transcription-translation. Like TNF-alpha, genistein inhibited induction of NOS protein by a second proinflammatory cytokine, interleukin-1beta, suggesting similar activation mechanisms by proinflammatory cytokines. NOS induction by other stimuli, including phorbol 12-myristate 13-acetate and the superoxide-generating system xanthine/xanthine oxidase, was also inhibited by genistein. Finally, cytokine-stimulated protein tyrosine kinase activity in hepatocytes was demonstrated by increased tyrosine phosphorylation of five high molecular mass protein bands. Genistein inhibited this cytokine-induced phosphotyrosine increase. The commonality of genistein inhibition suggests that protein tyrosine kinase activity is critical for NOS induction by a variety of stimuli.