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Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children

Lead (Pb) is neurotoxic and children are highly susceptible to this effect, particularly within the context of continuous low-level Pb exposure. A current major challenge is identification of children who may be uniquely susceptible to Pb toxicity because of genetic predisposition. Learning and memory are among the neurobehavioral processes that are most notably affected by Pb exposure, and modification of N-methyl-D-aspartate receptors (NMDAR) that regulate these processes during development are postulated to underlie these adverse effects of Pb. We examined the hypothesis that polymorphic variants of genes encoding glutamate receptor, ionotropic, NMDAR subunits 2A and 2B, GRIN2A and GRIN2B, exacerbate the adverse effects of Pb exposure on these processes in children. Participants were subjects who participated as children in the Casa Pia Dental Amalgam Clinical Trial and for whom baseline blood Pb concentrations and annual neurobehavioral test results over the 7 year course of the clinical trial were available. Genotyping assays were performed for variants of GRIN2A (rs727605 and rs1070503) and GRIN2B (rs7301328 and rs1806201) on biological samples acquired from 330 of the original 507 trial participants. Regression modeling strategies were employed to evaluate the association between genotype status, Pb exposure, and neurobehavioral test outcomes. Numerous significant adverse interaction effects between variants of both GRIN2A and GRIN2B, individually and in combination, and Pb exposure were observed particularly among boys, preferentially within the domains of Learning & Memory and Executive Function. In contrast, very few interaction effects were observed among similarly genotyped girls with comparable Pb exposure. These findings support observations of an essential role of GRIN2A and GRIN2B on developmental processes underlying learning and memory as well as other neurological functions in children and demonstrate, further, modification of Pb effects on these processes by specific variants of both GRIN2A and GRIN2B genes. These observations highlight the importance of genetic factors in defining susceptibility to Pb neurotoxicity and may have important public health implications for future strategies aimed at protecting children and adolescents from potential health risks associated with low-level Pb exposure.

By |2018-08-10T23:38:20+00:00January 1st, 2018|Other|

Clinical antibacterial effectiveness and biocompatibility of gaseous ozone after incomplete caries removal.

OBJECTIVES:
To evaluate local effect of gaseous ozone on bacteria in deep carious lesions after incomplete caries removal, using chlorhexidine as control, and to investigate its effect on pulp vascular endothelial growth factor (VEGF), neuronal nitric oxide synthase (nNOS), and superoxide dismutase (SOD).

MATERIALS AND METHODS:
Antibacterial effect was evaluated in 48 teeth with diagnosed deep carious lesion. After incomplete caries removal, teeth were randomly allocated into two groups regarding the cavity disinfectant used: ozone (open system) or 2% chlorhexidine. Dentin samples were analyzed for the presence of total bacteria and Lactobacillus spp. by real-time quantitative polymerase chain reaction. For evaluation of ozone effect on dental pulp, 38 intact permanent teeth indicated for pulp removal/tooth extraction were included. After cavity preparation, teeth were randomly allocated into two groups: ozone group and control group. VEGF/nNOS level and SOD activity in dental pulp were determined by enzyme-linked immunosorbent assay and spectrophotometric method, respectively.

RESULTS:
Ozone application decreased number of total bacteria (p = 0.001) and Lactobacillus spp. (p < 0.001), similarly to chlorhexidine. The VEGF (p < 0.001) and nNOS (p = 0.012) levels in dental pulp after ozone application were higher, while SOD activity was lower (p = 0.001) comparing to those in control pulp.

CONCLUSIONS:
Antibacterial effect of ozone on residual bacteria after incomplete caries removal was similar to that of 2% chlorhexidine. Effect of ozone on pulp VEGF, nNOS, and SOD indicated its biocompatibility.

CLINICAL RELEVANCE:
Ozone appears as effective and biocompatible cavity disinfectant in treatment of deep carious lesions by incomplete caries removal technique.

By |2018-08-08T23:26:14+00:00January 1st, 2018|Other|

Immunoexcitotoxicity as the central mechanism of etiopathology and treatment of autism spectrum disorders: A possible role of fluoride and aluminum.

Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain’s immune system, microglia, and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming. Children are exposed to such sequential immune stimulation via a growing number of environmental excitotoxins, vaccines, and persistent viral infections. We demonstrate that fluoride and aluminum (Al3+) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Al3+ appears among the key suspicious factors of ASD, fluoride is rarely recognized as a causative culprit. A long-term burden of these ubiquitous toxins has several health effects with a striking resemblance to the symptoms of ASD. In addition, their synergistic action in molecules of aluminofluoride complexes can affect cell signaling, neurodevelopment, and CNS functions at several times lower concentrations than either Al3+ or fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.

By |2019-06-05T22:57:20+00:00January 1st, 2018|Other|

Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum.

FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With the exception of extraneous proteins, no component safety testing is required for vaccines or vaccine schedules. The dosing of aluminum in vaccines is based on the production of antibody titers, not safety science. Here we estimate a Pediatric Dose Limit that considers body weight. We identify several serious historical missteps in past analyses of provisional safe levels of aluminum in vaccines, and provide updates relevant to infant aluminum exposure in the pediatric schedule considering pediatric body weight. When aluminum doses are estimated from Federal Regulatory Code given body weight, exposure from the current vaccine schedule are found to exceed our estimate of a weight-corrected Pediatric Dose Limit. Our calculations show that the levels of aluminum suggested by the currently used limits place infants at risk of acute, repeated, and possibly chronic exposures of toxic levels of aluminum in modern vaccine schedules. Individual adult exposures are on par with Provisional Tolerable Weekly Intake “limits”, but some individuals may be aluminum intolerant due to genetics or previous exposures. Vaccination in neonates and low birth-weight infants must be re-assessed; other implications for the use of aluminum-containing vaccines, and additional limitations in our understanding of neurotoxicity and safety levels of aluminum in biologics are discussed.

By |2018-08-09T23:02:24+00:00January 1st, 2018|Other|

Does providing dental services reduce overall health care costs?: A systematic review of the literature.

BACKGROUND:
The authors conducted a systematic review of the literature to assess the impact of dental treatment on overall health care costs for patients with chronic health conditions and patients who were pregnant.

TYPES OF STUDIES REVIEWED:
The authors searched multiple databases including MEDLINE, Embase, Web of Science, and Dentistry & Oral Sciences Source from the earliest date available through May 2017. Two reviewers conducted the initial screening of all retrieved titles and abstracts, read the full text of the eligible studies, and conducted data extraction and quality assessment of included studies.

RESULTS:
The authors found only 3 published studies that examined the effect of periodontal treatment on health care costs using medical and dental claims data from different insurance databases. Findings from the qualitative synthesis of those studies were inconclusive as 1 of the 3 studies showed a cost increase, whereas 2 studies showed a decrease.

CONCLUSIONS AND PRACTICAL IMPLICATIONS:
The small number of studies and their mixed outcomes demonstrate the need for high-quality studies to evaluate the effect of periodontal intervention on overall health care costs.

By |2018-08-06T23:07:14+00:00January 1st, 2018|Other|

Historical and Contemporary Perspectives on the Microbiological Aspects of Endodontics

The microbiota of the oral cavity plays a significant role in pulpal and periapical diseases. Historically, 100 years ago little was known on microbiota, but after a century of investigations, only now can many of the intimate secrets of microbial growth, expansion, persistence, communal activities, and virulence be revealed. However, with the capabilities of the microbiota for mutation, quorum sensing, and information transference, researchers are hard-pressed to keep up with both the changes and challenges that an amazingly wide range of bacterial species pose for both the scientist and clinician. Fortunately, the development and expansion of a vast array of molecular biological investigative techniques have enabled dentistry and its associated medical fields to attempt to keep pace with the wide and fascinating world of oral microbiology.

By |2019-05-29T00:14:05+00:00January 1st, 2018|Other|

Oral health status and its determinants among opiate dependents: a cross-sectional study

BACKGROUND:

In addition to numerous general health problems, drug dependents manifest various oral health disorders. Our aim was to investigate the oral health status and its determinants among in-treatment opiate dependents.

METHODS:

As part of a comprehensive cross-sectional survey on opiate dependents admitted to methadone maintenance centers in Tehran, Iran, we conducted a clinical study in two centers from different socioeconomic areas. A trained dentist conducted face to face interviews and clinical oral examinations based on World Health Organization (WHO) criteria for Decayed, Missing, Filled Teeth (DMFT) index and Community Periodontal Index (CPI) on volunteer patients. Student’s t-test, Mann-Whitney U, Kruskal Wallis, and Chi2 tests, in addition to linear and logistic regression models served for statistical analysis (p < 0.05).

RESULTS:

A total of 217 patients (98% men), with a mean age of 43.6 years (SD 12.3) participated in the study. Opium was the main drug of abuse reported by 70% of the participants followed by crystalline heroin (22%). Of the participants, 24.4% were totally edentulous. The mean DMFT score of participants was 20.3 (SD 7.8). Missing teeth comprised the main part of the index followed by decayed and filled teeth. Older patients (p < 0.001) and the patients with a lower socioeconomic status (p = 0.01) had higher DMFT scores. None of the dentate patients had a healthy periodontium. Maximum CPI mostly consisted of shallow pockets (66%) followed by calculus in 15%, deep pockets in 11%, and bleeding in 8% of the participants. Older participants (p = 0.02) and those who started drug abuse at a younger age (p = 0.01) were more likely to develop periodontal pockets.

CONCLUSIONS:

Opiate dependents had a poor oral health status in terms of the dentition status and periodontal health. Missing teeth comprised the main part of their dental caries history and none had a healthy periodontium. Oral health care should be integrated into the package of general health services available in treatment centers.

Vitamin D levels in patients with recurrent aphthous stomatitis

BACKGROUND:
Lower serum vitamin D levels, a major public health problem worldwide, has been found to be associated with various infectious diseases, cancers, autoimmune and dermatological diseases. The serum levels of vitamin D in patients with recurrent aphthous stomatitis are not clear. We investigated the vitamin D levels in patients with recurrent aphthous stomatitis.

METHODS:
Forty patients with recurrent aphthous stomatitis (Group I) and 70 healthy controls (Group II) included in the study. The characteristics of aphthous lesions (duration of disease and remission, frequency, diameter and number of the lesions) and demographics of the participants were recorded. Serum 25-hydroxycholecalciferol levels were measured using electrochemiluminescence binding method.

RESULTS:
There was no statistically significant difference between the groups in terms of age (p = 0.06) and sex (p = 0.4). Other baseline characteristics were not significantly different between the groups (p > 0.05 for all). The mean diameter of aphthous lesions was 0.5 (0.4-0.6) cm and the mean number of lesions was 2.2 ± 1.5. Serum vitamin D levels were 11 ± 7.04 ng/ml in Group I and 16.4 ± 10.19 ng/ml in Group II. Serum vitamin D levels were significantly lower in patients with recurrent aphthous stomatitis (p = 0.004).

CONCLUSIONS:
The present study showed lower vitamin D levels in patients with recurrent aphthous stomatitis compared to healthy controls.

By |2019-02-18T21:38:45+00:00January 1st, 2018|Other|

Oral manifestation of Langerhans cell histiocytosis: a case report.

BACKGROUND:
Bone necrosis of the jaw is a serious condition with a broad differential diagnosis of pathologies such as cutaneous histiocytosis, bone metastases or malignant tumours. In addition to the most common cause, medication related osteonecrosis of the jaw (MRONJ), one must consider a number of other causes, such as histiocytosis. Langerhans cell histiocytosis (LCH) is a histiocytic disorder with a large spectrum of clinical manifestations and with possible involvement of a variety of organs. This case shows the importance of an early detection of this rare disease in order to prevent further spreading. Even if an initial diagnosis in the oral cavity is rare, dentists should be aware of this disease.

CASE PRESENTATION:
The presented case describes a patient who was referred for evaluation and treatment due to exposed bone and extensive osteolysis in the region of the upper and lower jaw. After biopsy and diagnosis of LCH, the patient was treated with systemic therapy, achieved remission and is disease free after a 2 year of follow up.

CONCLUSIONS:
This case report illustrates that when dealing with unclear osteolytic changes of the jawbone, Langerhans cell histiocytosis must be taken into consideration in the differential diagnosis and biopsy must be performed in case of suspicion.

What factors affect the severity of permanent tooth impaction?

BACKGROUND:
The aim of this study was to investigate the association between the severity of permanent tooth impaction and a number of predefined factors, including tooth type, age, gender, tooth agenesis, microdontia of maxillary lateral incisor, and retained deciduous predecessors.

METHODS:
A sample of 2979 dental patients, aged 15 to 40 years, was surveyed by two calibrated examiners for permanent tooth impaction (excluding third molars). On panoramic radiographs, the impacted teeth were initially ranked based on their vertical, horizontal, and angular positions, and the ranking was then analysed for distribution by the predefined factors. To test the age factor, patients were divided into younger (15 to 25 yr) and older (between 25 and 40 yr) age groups. The statistical significance of the ranked vertical, horizontal, and angular positions of impacted teeth by the investigated factors was determined using the Wilcoxon-Mann-Whitney U test.

RESULTS:
The angular position of the impacted teeth was more severe in the older age group (P = 0.012) and in females (P = 0.018). The maxillary canine had more severe horizontal (P = 0.001) and angular (P = 0.003) impactions in females. Tooth agenesis was associated with less severe horizontal impaction (P = 0.041) in the mandibular second premolar. In addition, microdontia of the maxillary lateral incisor was associated with more severe horizontal impaction in general, and more severe horizontal (P = 0.024) and angular (P = 0.010) impaction of the mandibular second premolar in particular. Finally, our results showed that a retained deciduous predecessor was linked to a less severe vertical impaction of the mandibular second premolar (P = 0.030) and horizontal impaction of the maxillary second premolar (P = 0.037) but more severe angular impaction of the mandibular canine.

CONCLUSIONS:
This study suggests that the more delayed the treatment, being a female, the presence of maxillary lateral incisor with microdontia, and retained lower deciduous canines might be associated with more severe position of the impacted teeth. Because the severity of tooth impaction would follow different patterns when considering the investigated factors, it is mandatory to include such factors during dental diagnoses and the planning of preventive or interceptive interventions for young patients.

By |2019-02-18T21:27:36+00:00January 1st, 2018|Other|
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