Areca nut trade, globalisation and its health impact: perspectives from India and South-east Asia.

AIM:: Areca nut (AN) is consumed globally by 600 million people, and 10%-20% of the world population uses betel quid, a preparation containing areca nut. India and other South-east Asian countries are the largest consumers of AN in the world. The aim of this article is to review the economic impact and oral health effects of the consumption of AN. It will also discuss the role of dentists and auxiliary healthcare providers for increasing public awareness and the need for a strong public health policy. METHOD:: To address the concerned area, PubMed, Scopus and Google Scholar databases were explored from the year 1965 until 2017. Studies focusing on various aspects of AN only, and articles published in English were included. Anecdotal reports, case reports and unpublished data were excluded. RESULTS AND DISCUSSION:: This narrative review suggests India is the world's largest producer of AN along with the largest AN consuming population followed by other South-east Asian countries. AN chewing causes oral submucous fibrosis (OSF) and it is most commonly observed in people of India and South-east Asia. AN use is associated with various social and unsocial aspects. Dentists and dental auxiliaries can increase the knowledge and awareness of a health issue (OSF) among the target audience as well as the detrimental effects of AN chewing. CONCLUSION:: There is a need for more aggressive public health measures and dentists and dental auxiliaries should be employed to bring awareness to the general public regarding AN use.

Knowledge about human papillomavirus (HPV) related oral cancers among oral health professionals in university setting-A cross sectional study.

INTRODUCTION: Scientific literature suggests that human papillomavirus (HPV) infection may be associated with oral squamous cell carcinoma (OSCC). However, knowledge regarding HPV-OSCC link among oral health professionals (OHP) has been insufficient. So, the aim of this study was to assess the knowledge about HPV associated OSCC among OHP working in dental faculties in Malaysia. METHODOLOGY: Ethical committee of the University approved this study. A validated, pre-tested questionnaire was sent electronically to 224 OHP. Questionnaire collected information regarding demography, knowledge about HPV-OSCC link, HPV vaccine, and willingness to educate patients about HPV OSCC link among the participants of this cross-sectional study. Data collected was analysed using "Stata/IC-13" and was summarised using descriptive statistics like frequency, percentage, mean and standard deviation. RESULTS: Out of 179 participants, around 39% of the participant's opined virus was not a causative factor for OSCC. Around, 44% replied posterior portion of the tongue/oro-pharynx was the commonest site for HPV related OSCC, whereas 29% replied that lateral border of the tongue was the common site for HPV related OSCC. Forty one percent educated patients regarding HPV infection being a causative factor for OSCC. HPV vaccine can prevent OSCC was stated by 70% OHP. Only 12% were aware of the availability of HPV vaccine in Malaysia. Majority (99%), agreed that there is a need to offer continuing education programmes to dentists highlighting advances and preventive strategies in the fight against OSCC. CONCLUSION: Substantial increase in awareness is required among OHP regarding HPV-OSCC link.

Use of an Ex Vivo Porcine Mucosal Model to Study Superantigen Penetration.

In vitro perfusion studies are frequently used to determine the penetration of compounds through skin and mucosa. Porcine tissue has been shown to be an excellent model for human tissue in terms of structure, function, and reactivity. We describe the use of porcine tissue ex-vivo in a continuous flow perfusion system to study the behavior of superantigens in this model.

Potential applications of keratinocytes derived from human embryonic stem cells.

Although skin grafting is one of the most advanced cell therapy technique, wide application of skin substitutes is hampered by the difficulty in securing sufficient amount of epidermal substitute. Additionally, in understanding the progression of skin aging and disease, and in screening the cosmetic and pharmaceutical products, there is lack of a satisfactory human skin-specific in vitro model. Recently, human embryonic stem cells (hESCs) have been proposed as an unlimited and reliable cell source to obtain almost all cell types present in the human body. This review focuses on the potential off-the-shelf use of hESC-derived keratinocytes for future clinical applications as well as a powerful in vitro skin model to study skin function and integrity, host-pathogen interactions and disease pathogenesis. Furthermore, we discuss the industrial applications of hESC-derived keratinized multi-layer epithelium which provides a human-like test platform for understanding disease pathogenesis, evaluation of new therapeutic modalities and assessment of the safety and efficacy of skin cosmetics and therapeutics. Overall, we conclude that the hESC-derived keratinocytes have great potential for clinical, research and industrial applications.

Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal mucosa to toxic shock syndrome toxin-1.

Menstrual toxic shock syndrome (mTSS) is a rare, recognizable, and treatable disease that has been associated with tampon use epidemiologically. It involves a confluence of microbial risk factors (Staphylococcus aureus strains that produce the superantigen-TSST-1), as well as environmental characteristics of the vaginal ecosystem during menstruation and host susceptibility factors. This paper describes a series of experiments using the well-characterized model of porcine vaginal mucosa ex-vivo to assess the effect of these factors associated with tampon use on the permeability of the mucosa. The flux of radiolabeled TSST-1 and tritiated water ((3)H2O) through porcine vaginal mucosa was determined at various temperatures, after mechanical disruption of the epithelial surface by tape stripping, after treatment with surfactants or other compounds, and in the presence of microbial virulence factors. Elevated temperatures (42, 47 and 52°C) did not significantly increase flux of (3)H2O. Stripping of the epithelial layers significantly increased the flux of labeled toxin in a dose-dependent manner. Addition of benzalkonium chloride (0.1 and 0.5%) and glycerol (4%) significantly increased the flux of (3)H2O but sodium lauryl sulfate at any concentration tested did not. The flux of the labeled toxin was significantly increased in the presence of benzalkonium chloride but not Pluronic® L92 and Tween 20 and significantly increased with addition of α-hemolysin but not endotoxin. These results show that the permeability of porcine vagina ex-vivo to labeled toxin or water can be used to evaluate changes to the vaginal environment and modifications in tampon materials, and thus aid in risk assessment.

Restaurant volatility and the Iowa City, Iowa, smoke-free restaurant ordinance.

PURPOSE: To determine the economic impact of the Iowa City, Iowa, smoke-free restaurant ordinance (IC-SFRO) using an immediate and novel approach. DESIGN: In this retrospective study, food permit licensure served as the measure to assess the IC-SFRO impact. The Iowa City experience provided an excellent experimental setting, as the ordinance was enacted March 1, 2002, and repealed May 7, 2003, because of preemption. SETTING: The city of Coralville served as a natural control, as it is contiguous to Iowa City, has similar population demographics, and has never enacted a smoke-free restaurant ordinance. MEASURES: Food permit licensure data for all Iowa City and Coralville restaurants were obtained from the Johnson County Health Department. ANALYSIS: Differences in restaurant volatility were assessed using Fisher's exact probability test. RESULTS: The number of restaurants increased in both Iowa City and Coralville throughout the ordinance period. The ratio of the total number of restaurants in Iowa City to the total number of restaurants in the Iowa City-Coralville metropolitan area remained stable. The proportion of restaurants for each city did not differ significantly during the preordinance, ordinance, and postordinance periods. CONCLUSION: The IC-SFRO did not adversely impact the restaurant industry in terms of restaurant closures. The Iowa legislature was urged to draft evidence-based legislation, such as amending preemption of the IC-SFRO, to protect and promote the health of its communities.

Differentiation of human embryonic stem cells into clinically amenable keratinocytes in an autogenic environment.

Human embryonic stem cells (hESCs)-derived keratinocytes hold great clinical and research potential. However, the current techniques are hampered by the use of xenogenic components that limits their clinical application. Here we demonstrated an efficient differentiation of H9 hESCs (H9-hESCs) into keratinocytes (H9-Kert) with the minimum use of animal-derived materials. For differentiation, we established two microenvironment systems originated from H9-hESCs (autogenic microenvironment). These autogenic microenvironment systems consist of an autogenic coculture system (ACC) and an autogenic feeder-free system (AFF). In addition, we showed a stage-specific effect of Activin in promoting keratinocyte differentiation from H9-hESCs while repressing the expression of early neural markers in the ACC system. Furthermore, we also explained the effect of Activin in construction of the AFF system made up of extracellular matrix similar to basement membrane extracted from H9-hESC-derived fibroblasts. H9-Kert differentiated in both systems expressed keratinocyte markers at mRNA and protein levels. H9-Kert were also able to undergo terminal differentiation in high Ca(2+) medium. These findings support the transition toward the establishment of an animal-free microenvironment for successful differentiation of hESCs into keratinocytes for potential clinical application.

Fourth-year dental students' perceived barriers to providing tobacco intervention services.

In order to facilitate effective tobacco cessation services within dental school clinics, it is necessary to understand the perceived barriers encountered by dental students while providing these services. The aim of this study was to identify which factors fourth-year dental students perceive to be associated with barriers to providing tobacco intervention services. A written survey was developed and completed by incoming fourth-year dental students (a convenience sample of seventy students) at the University of Iowa College of Dentistry in 2008. The survey assessed the perceived barriers to providing tobacco intervention services and related factors. Descriptive, bivariate, and linear regression analyses were conducted. The response rate was 97 percent. The most frequently reported barriers were patients' resistance to tobacco intervention services (96 percent), inadequate time available for tobacco intervention services (96 percent), and forgetting to give tobacco intervention advice (91 percent). The following variables were significantly (p<0.05) related to greater perceived barriers in providing tobacco intervention services: lower "adequacy of tobacco intervention curriculum coverage of specific topics covered over the previous three years" and greater "perceived importance of incorporating objective structured clinical examination teaching method for learning tobacco intervention." Students probably could benefit from additional didactic training, but most important may be enhanced clinical experiences and faculty reinforcement to facilitate effective practical student learning and adaptation for future delivery of intervention services in private practice settings.

Effect of menthol on the penetration of tobacco carcinogens and nicotine across porcine oral mucosa ex vivo.

INTRODUCTION: Menthol is a flavored tobacco additive claimed to mask the bitter taste and reduce the harshness of cigarette smoke. (Azzi, C., Zhang, J., Purdon, C. H., Chapman, J. M., Nitcheva, D., Hebert, J. R., et al., 2006, Permeation and reservoir function of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the presence of ethanol and menthol. Carcinogenesis, 27, 137-145). have shown that menthol increased the flux of tobacco carcinogens (TC) across porcine esophagus. As oral mucosa is exposed to both smoke and smokeless tobacco in tobacco users, the objective of this study was to determine whether menthol influenced the penetration of the TC nitrosonornicotine (NNN) across porcine buccal (BM) and floor of mouth (FM) mucosa. METHODS: Porcine BM and FM were collected at slaughter, mounted in perfusion chambers (n = 7/group), and exposed to tritiated NNN ((3)H-NNN; Amersham, activity 1 muCi/ml) and tritiated nicotine ((3)H-nicotine; Sigma) in 3% nicotine/phosphate-buffered saline (0.01 M, pH 7.4) containing 0.01% unlabeled NNN (National Cancer Institute Chemical Carcinogen Repository) +/- 0.08% menthol for 0.5, 1, 2, or 12 hr. K(p) values (cm/min) were determined and statistically analyzed (analysis of variance, Tukey's, p < .05). RESULTS: FM and BM permeability to both (3)H-NNN and (3)H-nicotine was significantly increased (p < .05) with addition of menthol over that of nicotine alone regardless of exposure times. Even short 30-min menthol exposure significantly increased the flux of both compounds, and this was maintained throughout the experiment. DISCUSSION: Menthol enhances penetration of NNN and nicotine through FM and BM in vitro, even after short exposure. This may reflect loading of a superficial epithelial reservoir (Squier, C. A., Kremer, M. J., Bruskin, A., Rose, A., & Haley, J. D., 1999. Oral mucosal permeability and stability of transforming growth factor beta-3 in vitro. Pharmaceutical Research, 16, 1557-1563.), thus delivering menthol and enhancing flux for several hours. Practical implications are for a potentially increased oral exposure to carcinogens among users of menthol-flavored cigarettes and chewing tobacco.

Cytolysins augment superantigen penetration of stratified mucosa.

Staphylococcus aureus and Streptococcus pyogenes colonize mucosal surfaces of the human body to cause disease. A group of virulence factors known as superantigens are produced by both of these organisms that allows them to cause serious diseases from the vaginal (staphylococci) or oral mucosa (streptococci) of the body. Superantigens interact with T cells and APCs to cause massive cytokine release to mediate the symptoms collectively known as toxic shock syndrome. In this study we demonstrate that another group of virulence factors, cytolysins, aid in the penetration of superantigens across vaginal mucosa as a representative nonkeratinized stratified squamous epithelial surface. The staphylococcal cytolysin alpha-toxin and the streptococcal cytolysin streptolysin O enhanced penetration of toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, respectively, across porcine vaginal mucosa in an ex vivo model of superantigen penetration. Upon histological examination, both cytolysins caused damage to the uppermost layers of the vaginal tissue. In vitro evidence using immortalized human vaginal epithelial cells demonstrated that although both superantigens were proinflammatory, only the staphylococcal cytolysin alpha-toxin induced a strong immune response from the cells. Streptolysin O damaged and killed the cells quickly, allowing only a small release of IL-1beta. Two separate models of superantigen penetration are proposed: staphylococcal alpha-toxin induces a strong proinflammatory response from epithelial cells to disrupt the mucosa enough to allow for enhanced penetration of toxic shock syndrome toxin-1, whereas streptolysin O directly damages the mucosa to allow for penetration of streptococcal pyrogenic exotoxin A and possibly viable streptococci.

Novel toxic shock syndrome toxin-1 amino acids required for biological activity.

Superantigens interact with T lymphocytes and macrophages to cause T lymphocyte proliferation and overwhelming cytokine production, which lead to toxic shock syndrome. Staphylococcus aureus superantigen toxic shock syndrome toxin-1 is a major cause of menstrual toxic shock syndrome. In general, superantigen-secreting S. aureus remains localized at the vaginal surface, and the superantigen must therefore penetrate the vaginal mucosa to interact with underlying immune cells to cause toxic shock syndrome. A dodecapeptide region (toxic shock syndrome toxin-1 amino acids F119-D130), relatively conserved among superantigens, has been implicated in superantigen penetration of the epithelium. The purpose of this study was to determine amino acids within this dodecapeptide region that are required for interaction with vaginal epithelium. Alanine mutations were constructed in S. aureus toxic shock syndrome toxin-1 amino acids D120 to D130. All mutants maintained superantigenicity, and selected mutants were lethal when given intravenously to rabbits. Toxic shock syndrome toxin-1 induces interleukin-8 from immortalized human vaginal epithelial cells; however, three toxin mutants (S127A, T128A, and D130A) induced low levels of interleukin-8 compared to wild type toxin. When carboxy-terminal mutants (S127A to D130A) were administered vaginally to rabbits, D130A was nonlethal, while S127A and T128A demonstrated delayed lethality compared to wild type toxin. In a porcine ex vivo permeability model, mutant D130A penetrated the vaginal mucosa more quickly than wild type toxin. Toxic shock syndrome toxin-1 residue D130 may contribute to binding an epithelial receptor, which allows it to penetrate the vaginal mucosa, induce interleukin-8, and cause toxic shock syndrome.

Porcine vagina ex vivo as a model for studying permeability and pathogenesis in mucosa.

The vaginal mucosa is commonly exposed to a variety of topical agents, including chemical contraceptives, drugs for the treatment of specific pathological conditions, and pathogenic microorganisms. In vitro models can provide important information regarding the penetration and efficacy of topical compounds as well as the pathogenesis of various diseases such a menstrual toxic shock syndrome. Realistic and reproducible test systems are important if new agents are to fulfill their therapeutic potential in human populations. The selection of appropriate animal species and tissue and the use of valid in vitro systems can avoid many of the shortcomings of current animal and cell culture test systems. This review provides information about the factors that should be considered when selecting the best model to study the permeability of the human vagina. The characteristics of an ex vivo porcine model are explored and the validity of this model is demonstrated in terms of its histology, ultrastructure and composition and organization of the permeability barrier; data indicate excellent correlation of permeability and tissue response between human and porcine vaginal tissue.

Tobacco use, cessation advice to patients and attitudes to tobacco control among physicians in Ukraine.

To examine the relationship between physicians' smoking behaviors and their attitudes toward tobacco use by their patients and tobacco control in the Ukraine, a 70-item questionnaire was administered to 799 general practitioners (287 men and 512 women) working in both rural (278 physicians) and urban (521 physicians) areas of three regions of Ukraine. In all, 13.9% of physicians were current smokers and 21.6% reported being past smokers, with significantly (P<0.001) more men than women being current or past smokers. Odds ratios from logistic regression analysis reveal that physicians who are heavy smokers are 26% less likely to record tobacco use by patients than medium smokers. Heavy smokers devote significantly less effort to providing cessation information to patients and are 36% less likely to support the complete prohibition of smoking in the physician's workplace. Older physicians, female physicians and physicians working in urban areas are significantly more likely than younger, male and rural physicians to advise their patients on smoking. The provision of smoking cessation to patients by general practitioners in Ukraine is influenced by several factors, a major one being the smoking status of the physician. If smoking among physicians declines, this will encourage the patient to consider a serious quit attempt in several ways, most notably: (1) physicians act as societal role models and can promote non-smoking as a norm and (2) the likelihood that a patient will be provided smoking cessation counseling increases.

Cytokeratin changes in cell culture systems of epithelial cells isolated from oral mucosa: a short review.

In the past three decades, many studies have analyzed ultrastructural and molecular markers of differentiation in squamous stratified epithelial tissues. In these tissues, epithelial cells migrating from the basal layer to the upper layers undergo drastic changes, which involve membrane-associated proteins, DNA synthesis, phenotypic aspects, lipid composition, and cytoskeletal components. Cytoskeletal components include a large and heterogeneous group, including intermediate filaments, components of the cornified envelope, and of the stratum corneum. When grown in mono- and multilayer cell cultures, epithelial cells isolated from the oral mucosa may reproduce many of the biochemical and morphological aspects of epithelial tissue in vivo. In the present paper, we examine phenotypic changes, development of suprabasal layer, and Involucrin expression occurring in differentiating oral epithelial cells, based on literature review and original data.

Intercellular junctions in oral epithelial cells: ultrastructural and immunological aspects.

The activation of the molecular cascade leading to Ca++ -induced differentiation in cultured epithelial cells might be provided by the establishment of intercellular junctions between cells. In the present paper, we tested the hypothesis that Ca++ concentration would determine morphological and biochemical changes in intercellular junctions of cultured human gingival cells. Triplicate samples of monolayer cultures of human oral gingival cells were grown with two different Ca++ concentrations (0.3 and 1.8 mM), and examined by transmission (TEM) and scanning (SEM) electron microscopy at different time periods. To determine the role of the E-cadherin/beta-catenin complex in intercellular junction formation, oral epithelial cell cultures were grown in 0.3 mM Ca++ in presence of a blocking antibody anti human E-cadherin, stained with antibodies anti human beta-catenin, and examined by confocal laser scanning microscopy (CLSM). By TEM and SEM, cells grown at physiologic Ca++ concentrations (i.e., 1.8 mM) showed a subjective increase of the size of microvilli and of the number of intercellular junctions, which was more evident after 3 days in culture. Desmosome-like junctions were observed in cells grown in 1.8 mM Ca++, not in cells grown in 0.3 mM. By CLSM, development of intercellular adhesion was marked by membranous localization of E-cadherin and beta-catenin within the first hours in both culture types. When cell-cell adhesion was prevented, cells showed round shape and no membranous localization of beta-catenin. Restoring cell adhesion brought about polygonal cell shape and membranous localization of beta-catenin. We can conclude that increased Ca++ concentration may determine biochemical and morphological changes at membranous level in human oral epithelial cells. These changes may facilitate the development of intercellular junctions.

Factors related to utilization of dental services during pregnancy.

OBJECTIVES: The purposes of this study were to investigate factors related to utilization of dental services during pregnancy and to assess the extent of mothers' knowledge regarding oral health during pregnancy and its effect on pregnancy outcomes. MATERIALS AND METHODS: Cross-sectional data were collected from 625 women using a structured questionnaire mailed to mothers who had given birth in Johnson County, Iowa from August 2001 to March 2002. The survey assessed knowledge, behaviours, attitudes toward dental care during pregnancy, and personal, demographic and pregnancy-related factors. Variables which showed associations in bivariate analysis (p< or =0.1) were considered as candidates for building logistic regression models separately by domain (demographics, dental health care behaviours, lifestyle, financial variables, pregnancy-related variables, and knowledge of the possible association between oral health and pregnancy). Significant domain-specific regression results (p< or =0.05) were used to develop a final model using forward stepwise logistic regression analyses. RESULTS: The overall response rate was 69%. Dental visits during pregnancy were reported by 49% of respondents. Forty-three percent were aware of the possible connection between oral health and pregnancy outcomes. In the final logistic regression analysis, factors significantly associated with reporting dental visits during pregnancy were: (1) personal factors (being married, greater frequency of visiting the dentist when not pregnant and use of inter-proximal cleaning aids); (2) financial factors (dental insurance); and (3) knowledge of the possible connection between oral health and pregnancy outcomes. CONCLUSIONS: There was limited knowledge of the possible relationships between oral health and pregnancy outcomes in a fairly homogeneous population of women who were of relatively high socioeconomic standing. This study suggests that better education of the importance of dental care before and during pregnancy is needed.

The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1.

Despite knowledge of the effects of toxic shock syndrome (TSS) toxin 1 (TSST-1) on the adaptive immune system, little is known about stimulation of the innate immune system, particularly epithelial cells. This study investigated the interactions of TSS Staphylococcus aureus and TSST-1 with human vaginal epithelial cells (HVECs) and porcine mucosal surfaces. When cocultured with HVECs for 6 h, TSS S. aureus MN8 proliferated, formed aggregates on the HVEC surfaces, and produced exotoxins. Receptor binding studies showed that 35S-TSST-1 bound to 5 x 10(4) receptors per HVEC, with saturation at 15 min. Affymetrix Human GeneChip U133A microarray analysis determined S. aureus MNSM (100 bacteria/HVEC) caused at least twofold up- or down-regulation of 410 HVEC genes by 6 h; these data were also confirmed with S. aureus MN8. TSST-1 (100 microg/ml) caused up- or down-regulation of 2,386 HVEC genes by 6 h. In response to S. aureus, the HVEC genes most up-regulated compared to those in controls were those coding for chemokines or cytokines--MIP-3alpha, 478-fold; GRO-alpha, 26-fold; GRO-beta, 14-fold; and GRO-gamma, 30-fold--suggesting activation of innate immunity. TSST-1 also caused up-regulation of chemokine/cytokine genes. Chemokine/cytokine gene up-regulation was confirmed by enzyme-linked immunosorbent assays measuring the corresponding proteins induced by S. aureus and TSST-1. S. aureus MN8, when incubated with porcine vaginal tissue, increased the flux of 35S-TSST-1 across the mucosal surface. This was accompanied by influx of lymphocytes into the upper layers of the tissue. These data suggest innate immune system activation through epithelial cells, reflected in chemokine/cytokine production and influx of lymphocytes, may cause changes in vaginal mucosa permeability, facilitating TSST-1 penetration.

Prevalência do tabagismo entre adolescentes / Prevalence of smoking habits among adolescents

O hábito de fumar apresenta muitos efeitos nocivos aos tecidos bucais, sendo os efeitos precoces do tabagismo claramente evidenciados nos tecidos orais e faciais. Recentemente, tem crescido o interesse por estratégias para desestimular o início do hábito ou estimular o abandono do cigarro. Estudos sugerem que a maioria dos adultos fumantes iniciou o hábito antes dos 18 anos de idade. O objetivo deste estudo foi investigar a prevalência do tabagismo entre adolescentes, considerando os fatores relacionados ao início e a frequência do hábito de fumar, assim como a forma de aquisição do cigarro. Este estudo piloto foi desenvolvido com 98 adolescentes, com idade entre 12 e 18 anos, de ambos os sexos, estudantes de escolas públicas e particulares na cidade de Recife, Pernambuco. Os dados desta pesquisa foram obtidos através da aplicação de um questionário. Do total de adolescentes pesquisados, 33% provenientes de escola particular e 22% da escola pública afirmaram já terem experimentado o cigarro; e a idade em que o jovem fumou todo um cigarro pela primeira vez variou entre 11 e 16 anos. Apesar de um percentual significativo de jovens terem afirmado que já haviam experimentado cigarro, apenas 7,1% afirmara terem fumado nos últimos 30 dias. Faz-se necessária uma abordagem adequada pelo Odontopediatra com relação ao tagagismo na adolescência, podendo contribuir para prevenir o contato precoce com o hábito de fumar, assim como orientar seu abandono quando necessário.

Chitosan delivery systems for the treatment of oral mucositis: in vitro and in vivo studies.

Oral mucositis is a frequent and potentially severe complication of radiation or chemotherapy for cancer. Associated with atrophy and ulceration of the oral mucosa is an increased risk of infection, and the most common pathogenic agent is Candida. Chitosan is an excellent candidate for the treatment of oral mucositis. Its bioadhesive and antimicrobial properties offer the palliative effects of an occlusive dressing and the potential for delivering drugs, including anti-candidal agents. The aim of this study was to develop an occlusive bioadhesive system for prophylaxis and/or treatment of oral mucositis. Gel and film formulations were prepared using chitosans at different molecular weights and in different solvents. Nystatin, which is considered as a prophylactic agent for oral mucositis was incorporated into the formulations. The in vitro release of nystatin from the formulations was decreased with the increasing molecular weight of chitosan. The effect of the formulations was investigated in vivo in hamsters with chemotherapy-induced mucositis. Mucositis scores in groups treated with nystatin incorporated into gel and suspension formulations were significantly lower (p < 0.05) than those treated with the chitosan gel alone. Survival of animals in the treated groups was higher than that in the control group. The retention time and distribution of the gels in the oral cavity were investigated in healthy volunteers. A faster distribution of nystatin in the oral cavity was obtained using the suspension compared to the gels, but the nystatin saliva level decreased rapidly as well. A drug concentration above the minimum inhibitory concentration (MIC) value for Candida albicans (0.14 microg/ml) was maintained for longer periods of time at the application site (90 min) than at the contralateral site (45 min) in the oral cavity.