Functional assessment of peptide-modified PLGA nanoparticles against oral biofilms in a murine model of periodontitis.

The interaction of the periodontal pathogen Porphyromonas gingivalis (Pg) with commensal streptococci promotes Pg colonization of the oral cavity. Previously, we demonstrated that a peptide (BAR) derived from Streptococcus gordonii (Sg) potently inhibited adherence of Pg to streptococci and reduced Pg virulence in a mouse model of periodontitis. Thus, BAR may represent a novel therapeutic to control periodontitis by preventing Pg colonization of the oral cavity. However, while BAR inhibited the initial formation of Pg/Sg biofilms, much higher concentrations of peptide were required to disrupt an established Pg/Sg biofilm. To improve the activity of the peptide, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were surface-modified with BAR and shown to more potently disrupt Pg/Sg biofilms relative to an equimolar amount of free peptide. The goal of this work was to determine the in vivo efficacy of BAR-modified NPs (BNPs) and to assess the toxicity of BNPs against human gingival epithelial cells. In vivo efficacy of BNPs was assessed using a murine model of periodontitis by measuring alveolar bone resorption and gingival IL-17 expression as outcomes of Pg-induced inflammation. Infection of mice with Pg and Sg resulted in a significant increase in alveolar bone loss and gingival IL-17 expression over sham-infected animals. Treatment of Pg/Sg infected mice with BNPs reduced bone loss and IL-17 expression almost to the levels of sham-infected mice and to a greater extent than treatment with an equimolar amount of free BAR. The cytotoxicity of the maximum concentration of BNPs and free BAR used in in vitro and in vivo studies (1.3 and 3.4 µM), was evaluated in telomerase immortalized gingival keratinocytes (TIGKs) by measuring cell viability, cell lysis and apoptosis. BNPs were also tested for hemolytic activity against sheep erythrocytes. TIGKs treated with BNPs or free BAR demonstrated >90% viability and no significant lysis or apoptosis relative to untreated cells. In addition, neither BNPs nor free BAR exhibited hemolytic activity. In summary, BNPs were non-toxic within the evaluated concentration range of 1.3-3.4 µM and provided more efficacious protection against Pg-induced inflammation in vivo, highlighting the potential of BNPs as a biocompatible platform for translatable oral biofilm applications.

Effectiveness of a Mass Media Campaign on Oral Carcinogens and Their Effects on the Oral Cavity

Objective: To develop a mass media campaign on oral carcinogens and their effects on the oral cavity in order to increase awareness among the general population. Methods: Documentary and public service announcements highlighting the effects of tobacco and its products were designed and developed based on principles of behavior change. A questionnaire, designed to determine the knowledge, attitude and practice of people regarding oral carcinogens, was used to conduct a baseline survey at various sites in eastern Nepal. Local television channels and radio stations broadcasted the documentary and public service announcements. An evaluation survey was then performed to assess the effectiveness of the campaign. Results: Baseline and evaluation surveys covered 1,972 and 2,140 individuals, respectively. A third of the baseline population consumed quid, 22% chewing tobacco, 16% gutka (commercial preparation of arecanut, tobacco, lime and chemicals) and 25% cigarettes. Tobacco consumption differed significantly between 3 ecologic regions with greater use in the Terai region. The knowledge prevalence regarding the oral carcinogens quid (70%), chewing tobacco (82%), gutka (58%) and cigarettes (93%) significantly increased in the evaluation population. Females were more aware about the various tobacco products and their effects on health. More people knew about the harmful effects of tobacco on their health and oral cavity, and had their mouth examined and the frequency of consumption of these products reduced significantly after the campaign. Attitudes towards production, sale and advertisements of tobacco also improved significantly. Conclusions: The mass media campaign was an effective tool for increasing awareness among the population.

Assessment of oral and lung bioaccessibility of Cd and Pb from smelter-impacted dust.

Soil and dust contamination by metals engenders significant environmental and health problems in northern France where a lead smelter was in activity for more than a century. This study aims to examine the long-term effects of the smelter, 10 years after its closedown, on the presence of metal in sidewalk dust for a better assessment of the local population's exposure to Cd and Pb. The investigation included: (i) the metal distribution in different dust particle sizes and (ii) the assessment of metal bioaccessibility via ingestion and inhalation of dust. Seventy-two sidewalk dust samples were collected using a dust-sampling vacuum. The samples were sieved to collect different particle sizes from 0.3 to 1000 µm. The unified bioaccessibility method (UBM) was employed to evaluate the oral bioaccessibility of metals in the different particle sizes. The pulmonary bioaccessible fraction of Cd and Pb via the finest particles was extracted with lung-simulating solution (artificial lysosomal fluid). Ten years after the smelter closedown, (i) a strong relationship was observed between the concentrations of metals in dust and the distance to the former smelter, whatever the particle size; (ii) both total and oral bioaccessible concentrations of metals were high in the finest fraction (0.3-5 µm) and decreased when the particle size increased; (iii) a higher oral bioaccessibility of Cd and Pb was measured in the gastric phase (on average 43% for both metals for all particle sizes) and compared to the gastrointestinal phase (on average 16% for both metals for all particle sizes); and (iv) metal bioaccessibility via inhalation of dust was relatively high (on average 74 and 69%, for Cd and Pb, respectively). The results of the present study suggest that this environmental compartment may be a sensitive and effective indicator of anthropogenic metal contamination and the human exposure in urban areas.

Assessment of exposure to pesticides in rural workers in southern of Minas Gerais, Brazil.

The aim of the study was to assess of occupational exposure to pesticides in rural workers using genotoxicity test, bioindicators and clinical evaluation. Blood, urine and buccal samples from persons, rural workers exposed to a complex mixture of pesticides with organophosphates (n=94) and without organophosphates (n=94) were collected to compare the activities of cholinesterases, the levels of urinary dialkyl phosphates, genotoxicity data, from a cytome assay. Biomarkers were analysed by traditional/published methods Control group consisted of 50 other persons, non- occupationally exposed to pesticides from the city of Alfenas, Minas Gerais, Brazil. All subjects underwent a clinical evaluation. In the group exposed to organophosphates, the activity of acetylcholinesterase, butyrylcholinesterase and total cholinesterase was lower by 63.8%, 12.8%, and 14.8%, respectively, and 92.6% of the group had dialkyl phosphates present in their urine. The cytome assay was used to measure biomarkers of DNA damage (micronuclei and/or elimination of nuclear material by budding), cytokinetic defects (binucleated cells), and proliferative potential (basal cell) and/or cell death (condensed chromatin, karyorrhectic, pyknotic, and karyolytic cells). The group exposed to organophosphates showed significant changes in all these parameters compared to the control group and showed significant changes in budding, condensed chromatin and karyolytic cells compared with the group non-exposed to organophosphates. Data from the clinical evaluation showed significant changes in the central nervous, respiratory and auditory systems. The studied biomarkers are able to distinguish occupational and environmental exposure to pesticides and the data showed hazardous exposure to organophosphates and afforded valuable data to estimate the risk to cancer development.

Assessment of the mutagenic potential of arecoline in gpt delta transgenic mice.

Chewing the areca nut is carcinogenic to humans. Arecoline, a major alkaloid in areca nut, is suspected to be a carcinogenic component. It has been shown to have genotoxic potential in various in vitro systems; but information on its in vivo genotoxicity is limited. To investigate the organ-specific mutagenic potential of arecoline, we employed gpt delta transgenic mice to analyze the mutagenicity of arecoline in the oral tissues and liver. Male gpt delta mice were given arecoline hydrobromide in drinking water at 300 and 700µg/mL for 6 weeks. 4-Nitroquinoline-1 (4-NQO) was used as a positive control. Two weeks after the last treatment, mutation frequencies in the oral tissues (a mixture of gingival, buccal, pharyngeal and sublingual tissue) and liver were detected and mutation spectra were analyzed. There were no statistically significant differences in the average mutation frequencies between arecoline-treated and untreated groups in both the oral tissues and liver. However, in the oral tissues, one mouse in arecoline-300µg/mL group and two mice in arecoline-700µg/mL group showed more than 2.5-fold higher mutation frequencies than the untreated group; they also exhibited unique mutation spectra compared to spontaneous mutation types. In these three mice, all mutations occurred at G:C sites, where G:C→T:A transversions were most frequent, followed by G:C→A:T transitions and G:C→C:G transversions. The main type of spontaneous mutation in both the oral tissues and liver was G:C→A:T transition. These results suggest that arecoline poses a mutagenic hazard in the oral tissues of gpt delta transgenic mice.

Toxicological properties and risk assessment of the anionic surfactants category: Alkyl sulfates, primary alkane sulfonates, and α-olefin sulfonates.

The category of the anionic surfactants (ANS) consisting of 46 alkyl sulfates, 6 primary alkane sulfonates, and 9 α-olefin sulfonates has been assessed under the high production volume (HPV) chemicals program of the Organisation for Economic Cooperation and Development (OECD) in 2007. In this review the toxicological properties of these chemicals are summarized. The chemicals of this category are used predominantly in detergents, household cleaning products, and cosmetics. These chemicals show low acute and repeat dose toxicity. There was no evidence of genetic or reproductive toxicity, or carcinogenicity. There also was no indication for sensitizing properties. Skin and eye irritating effects in consumers are not to be expected. For consumers, the calculated body burden is about 10,000 times lower than the lowest NOAEL value in experimental animals, so that adverse effects caused by substances of the ANS category can be excluded.

Toxicological assessment of Ricinus communis Linn root extracts.

Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000 mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000 mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.

Assessment of oral complications in children receiving chemotherapy.

The aim of this study was to assess the early oral complications in pediatric patients receiving chemotherapy. An interview and oral examination was conducted on 150 pediatric cancer patients receiving standard dose chemotherapy. Results showed that oral pain and dry mouth were the most frequent patients' complaints. The prevalences of chemotherapy-induced oral mucositis and oral infections were relatively high. The chemotherapeutic antimetabolites were the most frequently associated with oral complications than other types of chemotherapy. The present results indicate that the oral complications among patients receiving chemotherapy are common.

[Assessment of the dental status, acid-base balance in the oral cavity and Ph of the gastric medium during the use of the Dirol chewing gum]. / Otsenka stomatologicheskogo statusa, kislotno-shchelochnogo ravnovesiia polosti rta i pH zheludochnoi sredy pri ispol'zovanii zhevatel'noi rezinki Dirol.

The goal of our research was to study the short-term and long-term effects of the Dirol chewing gum on the oral cavity state and acid-forming stomach function in patients with hyperchlorhydria. It was revealed that the rational use of this chewing gum by patients with increased gastric secretion can normalize the gastric acidity. Another result of the use of this chewing gum is the improvement of the oral cavity hygienic state and reduced growth of dental caries.

A simple method for screening assessment of acute toxicity of chemicals.

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2-2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.