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Background: Betel quid (BQ) is the fourth most commonly used psychoactive substance and its use is highly prevalent among southeast Asian countries due to the influence of psychosocial, behavioral, and environmental factors. As a result, even young children and women are becoming addicted and find it difficult to achieve long-term abstinence. Systematic research addressing the influence of behavioral and psychosocial factors on BQ chewing is scarce, hence pointing to the need for understanding the interplay of these factors to develop tailored intervention strategies for BQ cessation., Objective: The objective of this systematic review is to assess various behavioral and psychosocial risk factors from pre-existing literature that lead individuals to initiate and/or maintain BQ chewing in developed and developing countries., Materials and Methods: The electronic retrieval systems and databases PUBMED [MEDLINE], EMBASE, SCOPUS, WEB OF SCIENCE, GOOGLE SCHOLAR, and SCIENCE DIRECT were searched independently by two authors for relevant articles from January 2011 to July 2021 using combinations of keywords. Primary studies published in English focusing on the behavioral and psychosocial risk factors for BQ chewing were included., Results: Out of the initial 264 articles searched, 12 articles met the selection criteria. Included studies addressed the influence of behavioral and psychosocial factors toward the initiation and/or maintenance of BQ chewing. Included studies reported that dependent BQ was not able to quit BQ chewing due to habituation, addiction, and withdrawal symptoms. Few social BQ chewers in Southeast Asian countries were not willing to initiate quitting as they considered AN as an important social and cultural identifier and claimed that they could not resist chewing in a peer group, and it has become part of their social life., Conclusion: In the future, studies should take into consideration behavioral and psychosocial risk factors, which are major barriers toward successful quitting. These factors should be integrated into areca nut cessation guidelines, and there is a need to develop more comprehensive culture-specific intervention approaches to achieve long-term abstinence.

• Pathogenesis has never been addressed from the perspective of the physical properties of amalgamated betel quid (BQ) with saliva. • Mechanisms related to high osmotic pressure and hygroscopicity of amalgamated BQ are proposed. • Extracellular fluid loss is expected due to the high osmotic pressure and hygroscopicity of amalgamated BQ. • Dense fibrotic bundles observed in oral submucous fibrosis are a manifestation of such extracellular fluid loss, which brings fibers to close together. Increased production and decreased degradation of collagen fibers are the two of hallmarks of oral submucous fibrosis (OSMF). To date pathogenesis of OSMF has been perceived from the perspective of chemical constituents of the betel quid (BQ) and their impact on the signaling pathways related to fibrosis. In the present paper, physical properties such as osmotic pressure and hygroscopicity of the BQ amalgamation formed in the oral cavity are proposed as the causative mechanisms for OSMF. The detailed mechanism of osmotic pressure gradient development between extracellular fluid and the amalgamated BQ in the oral cavity has been deliberated. In addition, the hygroscopicity of BQ is also projected as a complementary mechanism to the osmotic pressure mechanism for OSMF development. Various laboratory experiments, cell culture models, and animal studies are proposed to evaluate the hypothesis. Since OSMF can also occur in only areca nut chewing individuals, we put forth the proposed mechanism as complementary to the already known pathogenesis. This novel hypothesis addresses the age-old problem related to the management of OSMF and extracellular fluid restoration strategies would drastically change and probably improve the clinical status and reduce the malignant potential of OSMF. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to investigate the rate of simultaneous second primary tumor (SPT) in patients with oral squamous cell carcinoma. The survival of patients with simultaneous SPT was also compared with patients without. Methods The presence of SPT was documented along with the patients' demographic data, tumor-related features, and survival status. Kaplan-Meier method was used for survival analysis. Relevant factors influencing the survival were examined by the Cox proportional hazard model. Results A total of 897 patients' medical records were obtained. Among them, 43 patients (4.8%) had simultaneous SPT and their prognosis was poorer than that of patients without. The Cox proportional hazard model revealed that patients with simultaneous SPT tended to have a higher probability of death (relative risk [RR], 1.694; p = .015). Conclusions Simultaneous SPT is an independent prognostic factor for patients with oral squamous cell carcinoma. Those with simultaneous SPT have poorer survival when compared to those without. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1801-1807, 2013 [ABSTRACT FROM AUTHOR]

Background: This cross sectional study aimed to compare the differences of means score of oral health related quality of life by OHIP-14 among teeth status, general characteristics and daily oral practices among elderly at Purbagram village, Bangladesh. Materials and Methods: A total of 172 elderly about and over 60 years were selected by accidental sampling from Purbagram village. Dental examination to assess teeth status was conducted. Short form of OHIP-14 questionnaire was applied to collect data by interview. Statistics were presented in number and percentage, mean, median, standard deviation, students T-test and ANOVA. Results: The result of the study revealed that more than half of the respondents had 20-28 good teeth (61.4%). Very few of the respondents wear denture (1.7%). More than half of the respondents never brushed their teeth in the morning (64.5%). One-third of the respondents used tooth paste (34.3%). Less than one-third of the respondents were used to smoke regularly (27.9%) Half of the respondents always took betel quid (50.9%). overall mean score of OHIP-14 of the respondents was 22.33 ± 11.29(SD), highest percentage was the item number 7 (poor diet) followed by item number 2 (worsened taste) and item number 4(Discomfort eating food). Only 1.2% of the respondents reported item number 4 very often (inability in function). Item number 14 reported as never more frequently (53.5%) followed by item number 1 (trouble pronouncing words, 52.9%) and 10 (Embarrassment, 52.9%) followed by item number 5 (Feeling self-conscious, 47.1%). Conclusion: The result shows that the mean score of OHIP-14 among the respondents who have 1-19 teeth were higher than who have 20-28 teeth. Elderly with 20-28 teeth had lowest means score of OHIP-14 with the best quality of life related to oral health compare to others. [ABSTRACT FROM AUTHOR]

Background There are 600 million betel quid chewers around the world. betel quid chewing is a major risk factor of oral cancer. Why betel quid components induce oral cancer is not clear. Methods Cytotoxicity of areca nut extract and arecoline (an areca nut alkaloid) to SAS oral epithelial cell line was evaluated by trypan blue dye exclusion and MTT assays. Cell cycle distribution and apoptosis was analyzed by propidium iodide staining flow cytometry. Chk1 and chk2 activation was analyzed by Pathscan phospho-enzyme-linked immunosorbent assay. Metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase (TIMPs) production was measured by enzyme-linked immunosorbent assay. Results Areca nut extract (800 μg/mL) and arecoline (>0.4 mmol/L) caused cell death, apoptosis, and cell cycle arrest of SAS cells. Areca nut extract and arecoline stimulated Chk1 and Chk2 phosphorylation in SAS cells. Areca nut extract stimulated cellular MMP-9 but suppressed TIMP-1 and TIMP-2 production. Conclusions Areca nut components activate Chk1/Chk2, alter cell cycle regulation/apoptosis, MMP-9, and TIMPs production, contributing to the pathogenesis of oral carcinogenesis. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Background: A variety of oral mucosal lesions and conditions are associated with the habit of smoking and chewing tobacco, and many of these carry a potential risk for the development of cancer. There have been no studies that report the prevalence of habits and associated oral changes in the population in Dharwad region, of Karnataka, south India. Materials and Methods: A hospital-based, cross-sectional study was carried out at SDM Dental College (Dharwad, Karnataka). A total of 2400 subjects (1200 subjects with and 1200 subjects without habits) attending the dental hospital were interviewed and examined by trained professionals to assess any oral mucosal changes. Results: Oral mucosal lesions were found in 322 (26.8%) subjects who had tobacco smoking and chewing habits as compared to 34 (2.8%) subjects without those habits. Oral leukoplakia (8.2%) and oral submucous fibrosis (OSF) (7.1%) were the prevalent oral mucosal lesions found in subjects who had those habits, while the other lesions (1.7%) namely; oral candidiasis, median rhomboid glossitis, recurrent apthous ulcer, frictional keratosis, and oral lichen planus (0.9%) were frequently reported among individuals without those habits. The odds of developing oral lesions in subjects with tobacco habits was nearly 11.92 times that of abstainers (odds ratio, OR = 11.92, 95% confidence intervals, CI = 10.61-14.59%). Conclusion: The study showed that the risk of the development of oral lesions associated with tobacco smoking, chewing, or both is quite high. Males who had one or more of these habits showed more frequent oral changes than females. The study reinforces the association of OSF with gutkha and areca nut chewing, and leukoplakia, erythroplakia, and oral cancer with tobacco smoking, chewing, or mixed habits. [ABSTRACT FROM AUTHOR]

Ten percent of the world's population use betel quid, making betel quid the fourth most used substance in the world. In Taiwan, there are an estimated 1.5 million users and the majority of them are also smokers. The number of people who died from oral cancer rose more than five times over the period from 1987 to 2006. In this study, we employ propensity score matching and the Weibull hazard model with instrumental variables to examine the health effects of betel quid chewing, in particular the health effect of its combined use with cigarettes. We show that betel quid chewing and smoking have a significant negative effect on health, and that the 10-year death hazard for joint users of betel quid and cigarettes doubles that for abstainers. Moreover, betel quid chewing is as harmful to health as smoking. We also find that betel quid chewing and smoking significantly increase the odds of dying from oral and oesophagus cancers. [ABSTRACT FROM AUTHOR]

Objective: To correlate the clinico-pathological aspects of Oral Squamous Cell Carcinoma (OSCC) with risk factors to determine the present status and variations in the profile. Methodology: One hundred patients of OSCC and one hundred age and sex matched controls were selected. Detailed demographic data, regarding age, gender, marital status, ethnicity, religion, socioeconomic status along with habits, betel quid, tobacco chewing / smoking, alcohol and dietary habits was recorded. Detailed oral examination was carried out for the site of involvement and associated pathology. Histological grade was determined on microscopic examination of Hemotoxylin & Eosin (H&E) stained slides. One hundred age and sex matched controls were also evaluated for this study. Results: Ages of patients ranged from 25 to 80 years with mean age being 47.84 ± 12.18(SD). Maximum cases were detected in the fifth decade. Male: Female ratio was 2.8:1. Age in controls ranged from 22 -73 with male to female ratio being 3.54:1. In patients, most tumors were seen in buccal cavity (54%) followed by tongue (24%). Histologically 60% cases were well differentiated. Strong association with tobacco smoking and chewing, betel quid and its substitutes was detected, with smoking being more prevalent in males and betel quid in females. Significantly less number of controls were observed to be involved in these habits, with almost half having no such addictions. Conclusion: The present clinico-pathological status of oral cancer still emphasizes primary prevention by creating awareness against the devastating effects of tobacco use, betel quid, its substitutes and areca nut, which can go a long way in decreasing the incidence of this disfiguring and lethal condition. [ABSTRACT FROM AUTHOR]

Objectives: Oral submucous fibrosis (OSF) is a chronic oral precancerous disease primarily caused by betel quid chewing. Some OSF patients are concomitant with oral lichenoid lesion (OLL), a white-streak lesion with a higher risk for cancerization, in OSF mucosa. Immunological reaction has been considered as one of their common pathogenic mechanisms. Cys-X-Cys ligand 9 (CXCL9) is an important factor to recruit effector neutrophils and lymphocytes in immunological reactions. However, the expression levels of CXCL9 in OSF and OLL remain unclear. Materials and methods: We investigated the expression levels of CXCL9 in 10 normal buccal mucosa (NBM) samples and 56 OSF concomitant with OLL patients, and evaluated the possible mechanism of CXCL9 on their pathogenesis. Results: Our results showed NBM demonstrated negative CXCL9 expression. OSF stained positive CXCL9 mainly in the cytoplasm of inflammatory cells and endothelial cells throughout the superficial layer of connective tissue, while its concomitant OLL showed much stronger CXCL9 in all mononuclear cells of subepithelial inflammatory infiltration ( p = 0.0006). There was an upregulated trend of CXCL9 expression from NBM to OSF to OLL. However, no significant association between CXCL9 expression and clinicopathologic parameters of patients was found. Conclusions: In conclusion, CXCL9 was found for the first time to contribute to the immunological pathogenesis for both OSF and its concomitant OLL, indicating a continuously enhanced intensity of immunoreactivity in their pathogenic process. Clinical relevance: CXCL9 might be a useful tool to monitor the phase and disease severity of OSF and OLL, and a potential target for further clinical therapy for both lesions. [ABSTRACT FROM AUTHOR]

Areca nut (AN) is consumed by millions of people for its therapeutic and psychoactive effects, making it one of the most widely self-administered psychoactive substances in the world. Even so, AN use/abuse is associated with myriad oral and systemic side effects, affecting most organ systems in the body. Alkaloids abundant in the nut (e.g. arecoline, arecaidine, guvacoline, and guvacine), collectively called the areca alkaloids, are presumably responsible for the major pharmacological effects experienced by users, with arecoline being the most abundant alkaloid with notable toxicological properties. However, the mechanisms of arecoline and other areca alkaloid elimination in humans remain poorly documented. Therefore, the purpose of this review is to provide an in-depth review of areca alkaloid pharmacokinetics (PK) in biological systems, and discuss mechanisms of metabolism by presenting information found in the literature. Also, the toxicological relevance of the known and purported metabolic steps will be reviewed. In brief, several areca alkaloids contain a labile methyl ester group and are susceptible to hydrolysis, although the human esterase responsible remains presumptive. Other notable mechanisms include N -oxidation, glutathionylation, nitrosamine conversion, and carbon-carbon double-bond reduction. These metabolic conversions result in toxic and sometimes less-toxic derivatives. Arecoline and arecaidine undergo extensive metabolism while far less is known about guvacine and guvacoline. Metabolism information may help predict drug interactions with human pharmaceuticals with overlapping elimination pathways. Altogether, this review provides a first-of-its-kind comprehensive analysis of AN alkaloid metabolism, adds perspective on new mechanisms of metabolism, and highlights the need for future metabolism work in the field.

Introduction: TikTok has gained increasing popularity over the past year. The social media may affect awareness and perceptions of betel quid (BQ) and smokeless tobacco (SLT) by utilizing content generated by TikTok users. The purpose of this study is to examine how BQ and SLT are portrayed on TikTok., Methods: The 28 most viewed hashtag-based keywords were used to identify popular BQ and SLT-related videos on TikTok (n=513) from June 2018 to September 2021. Two researchers independently coded the number of likes, shares, views, user category and themes., Results: A final sample of 513 videos containing BQ and SLT that met the study criteria were included. Collectively, these videos were viewed over 725 million times, with a median 'view' count of 17,300 (range 152-155,000,000) and a median 'likes' count of 831 (range 4-2,400,000) and a median 'share' count of 21 (range 0-48,400). Majority of the videos showed BQ and SLT use positively i.e promoting the product (390/513; 76%) and these had more than 686 million times views. Neutral depictions of BQ and SLT use were viewed 15 million times (72/513; 14%) and negative portrayals of BQ and SLT have been viewed 193 million times (105/808; 13%). The video themes included 'life style' (349/513; 68.0%), 'marketing' (62/513; 12.09%), 'comedy' (44/513; 8.6%), 'warning' (25/513; 4.87%), 'awareness' (12/513; 2.3%), 'sports and other' (12/513; 2.3%) and social events or culture (9/513; 1.75%)., Conclusion: Our results demonstrated that video clips related to BQ and SLT on TikTok, a fast-growing, popular video-sharing platform among teens, which is available with no age restrictions has been viewed multiple times. Majority (76%) promoted these two products, that could be detrimental to oral health. Therefore, the age restrictions especially for the videos containing BQ and SLT is mandatory in order to reduce the potential exposure of adolescents/young adults.

Consumption of areca nut alone, or in the form of betel quid (BQ), has negative health effects and is carcinogenic to humans. Indonesia is one of the largest producers of areca nuts worldwide, yet little is known about the biomolecular composition of Indonesian areca nuts and BQs. We have recently shown that phenolic and alkaloid content of Indonesian BQs exhibits distinct geographical differences. Here, we profiled for the first time the metabolomics of BQ constituents from four regions of Indonesia using non-targeted gas chromatography-mass spectrometry (GC-MS) analysis. In addition to well-known alkaloids, the analysis of small-molecule profiles tentatively identified 92 phytochemicals in BQ. These included mainly benzenoids and terpenes, as well as acids, aldehydes, alcohols, and esters. Safrole, a potentially genotoxic benzenoid, was found abundantly in betel ( Piper betle ) inflorescence from West Papua and was not detected in areca nut samples from any Indonesian region except West Papua. Terpenes were mostly detected in betel leaves and inflorescence/stem. Areca nut, husk, betel leaf, the inflorescence stem, and BQ mixture expressed distinctive metabolite patterns, and a significant variation in the content and concentration of metabolites was found across different geographical regions. In summary, this was the first metabolomic study of BQs using GC-MS. The results demonstrate that the molecular constituents of BQs vary geographically and suggest that the differential disease-inducing capacity of BQs may reflect their distinct chemical composition.

Natural products and traditional ethnomedicines are of great effect in therapeutics. Such types of medicine have been practiced in certain areas of the world to treat different health conditions. This pilot investigation aims to review the cumulative health effect of addendums used in betel quid such as areca nut, lime, and tobacco-associated betel quid chewing and without tobacco-associated chewing. This review shows that betel leaf extract and its essential oil could inhibit growth of microbes and damage different gram-positive and gram-negative bacteria as well as various fungus species. Some studies concluded that the combination of Piper leaves essential oil with antibiotics have potential effect on oral microorganisms. Long-term consumption of betel quid with tobacco is known to cause cancer, chromosomal aberrations, and pharynx tumors. However, consumption of betel leaf without tobacco has health benefits because of ethnomedicinal properties. Its essential is oil utilized as raw material for perfumes and mouth fresheners manufacturing. Scientific researches on this plant revealed that it possesses many beneficial activities to be used for developing novel drugs. However, compounds of betel leaves have beneficial natural antioxidant. Chewing and intake of leaves have effect on moving parts of salivary gland which is the main step of digestion. Its components also act as heartbeat regulators in relaxing the blood vessels to reduce hypertension. So this review discussed the natural compounds of betel leaves which is used as traditional medicine to further develop drug discovery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction., (© 2022 Society for the Study of Addiction.)

Areca nut chewing is one of the major risk factors for oral cancer, with large-magnitude risks reported in studies comparing betel quid chewers and never users, and it has been evaluated as a group 1 carcinogen by the International Agency for Research on Cancer. Data from a high-quality meta-analysis examining risk estimates are presented in summary form with additional information from more recent studies (pooled adjusted relative risk, 7.9; 95% CI, 7.1 to 8.7). The risk of oral cancer increases in a dose-response manner with the daily number of quids consumed and the number of years chewing. In the Indian subcontinent and in Taiwan, approximately half of oral cancers reported are attributed to betel quid chewing (population attributable fraction, 53.7% for residents in Taiwan and 49.5% for the Indian population), a disease burden that could be prevented. Oral leukoplakia and oral submucous fibrosis are 2 main oral potentially malignant disorders caused by areca nut chewing that can progress to oral cancer with continued use. Ex-chewers seem to demonstrate lower risks than current chewers, but the impact of areca nut cessation on oral cancer risk has not been scientifically evaluated on the basis of randomized controlled studies. These data strongly reconfirm that betel quid chewing, primarily areca nut use, should be taken into account in assessing the cancer risk of South Asian, East Asian populations and Pacific Islanders for the development of oral cancer.

Background: The nut of Areca catechu (areca nut) and the extract of leaves and barks of Uncaria gambir (gambir) are wrapped in Piper betle leaf making the ingredients of what the Malaysian called “sireh” or betel quid. Sometimes calcium hydroxide is added to it. It has been reported that the respective ingredients of betel quid except calcium hydroxide have wide spectrum of therapeutic and antioxidant properties. The aim of this study was to investigate the antioxidant and cytoprotective activities of the respective ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their cytoprotective and antioxidant activities with phenolic content was also determined. Methods: Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyszed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Results: Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and cytoprotective activity (r = 0.682). Conclusions: The betel quid has higher TPC, and antioxidant and cytoprotective activities than betel quid with calcium hydroxide. The quinic acid in betel quid may play an important role in the oral health protection. [ABSTRACT FROM AUTHOR]

Abstract: Cancer of the oral cavity is one of the most commonly diagnosed cancers and one of the leading causes of death among men in Taiwan. Extensive research findings have linked betel quid chewing with oral cancer and precancerous conditions. To date, no pharmacological or behavioral treatments exist for betel quid cessation. This paper discusses the potential benefits of applying behavioral research to better understand why betel quid chewers consume betel quid. Specifically, it discusses using behavioral research methods to examine betel quid chewing initiation, dependence, motivation, and withdrawal. Better understanding of these different aspects of betel quid chewing is likely to aid researchers in developing treatment programs. [Copyright &y& Elsevier]

Betel quid ( BQ) and areca nut chewing is widely prevalent in many parts of Asia and Asian-migrant communities throughout the world. Global reports estimate 600 million users. Sufficient evidence of carcinogenicity has been found for BQ and its main ingredient, areca nut. BQ areca nut users have an increased risk of potentially malignant disorders. Among chewers, BQ remains in contact with the oral mucosa for prolonged periods. This review examines the clinical and pathological aspects of lichenoid lesions caused by areca nut and BQ, a condition that has received little attention in the published literature. [ABSTRACT FROM AUTHOR]

ABSTRACT Few studies have investigated whether genetic abnormalities predispose individuals to heavy betel quid (BQ) use. One of the major ingredients of BQ, arecoline, is known to affect the expression of monoamine oxidase A ( MAO-A). We investigated the extent to which arecoline inhibits MAO-A expression and the role of MAO-A polymorphisms in BQ use in Taiwanese aborigines. Cytotoxicity assays, microarrays and quantitative reverse transcriptase-polymerase chain reaction were used to examine the effects of arecoline and areca nut extract (ANE) on cell viability and MAO-A expression in neuroblastoma SH-SY5Y cells. After identifying the effective concentrations of arecoline and ANE in vitro, we examined the in vivo effects of these compounds using a rat model system. Our results indicate that arecoline and ANE inhibit MAO-A expression both in vitro and in vivo. In addition, we examined the correlation between plasma MAO-A activity and cumulative exposure to BQ in humans. We recruited 1307 aborigines from a large-scale community-based survey to determine whether MAO-A variants were associated with high BQ use and a preference for use with smoking or alcohol and whether gender bias existed. MAO-A expression was significantly downregulated by arecoline and ANE at 100-200 µg/ml and in rat whole brains on days 30 and 45. MAO-A activity levels in human plasma were positively correlated with the extent of BQ exposure, and individuals with at-risk alleles exhibited lower activity, although this result did not reach statistical significance. We found two single nucleotide polymorphism (SNPs) in aboriginal males [rs2283725, odds ratio (OR) = 2.04; rs5953210, OR = 2.03] and females (rs2283725, OR = 1.54; rs5953210, OR = 1.59) that were associated with heavy BQ use. Those individuals carrying at-risk alleles who drank alcohol were twice as likely to be heavy BQ users. However, the effects of these SNPs on BQ use were significant even after controlling for alcohol use. Our results suggest that two specific loci may confer a susceptibility to BQ abuse and affect MAO-A enzymatic activity. [ABSTRACT FROM AUTHOR]

Background: Areca-nut (AN) chewing habit has been associated with oral diseases including oral cancer, oral submucous fibrosis and periodontal disease; however, some authors have reported that the AN-chewing abuse may also jeopardize the systemic health among its users. Objectives: The objective was to review any reported association between AN-chewing and the metabolic syndrome (MetS). Methods: To address the research question “Is there an association between areca-nut chewing habit and the MetS?” the MEDLINE and PubMed databases were searched from 1991 up to and including April 2010. The search criteria included: human studies, metabolic syndrome, diabetes, areca nut (AN). Only articles published in English were included. Results: Eight cohort studies were included in the review. The sample size of the selected studies ranged from 210 to 56,116 individuals (age range 15-83 years). The daily frequencies of AN-chewing reported by the users ranged between once a day to 76 times daily. The duration of use ranged from 6 years to ≥ 20 years. Two studies associated AN-chewing habit with hyperglycemia and type 2 diabetes while five studies studies reported an association between AN-chewing and metabolic syndrome. Four studies related AN-chewing with obesity and an increased body mass index. Higher triacylglycerol levels were reported in one study among AN-chewers compared to non-chewers. Though the numbers of publications on this subject are limited, the available studies indicate that AN-chewing could be associated with the metabolic syndrome, and individually with two of the recognized components of the syndrome i.e. diabetes mellitus and central obesity. [ABSTRACT FROM AUTHOR]

Arecanut (AN) usage is widespread in Asian countries, especially India and Taiwan. The incidence of oral cancer is increasing day by day, but there is no exponential increase with tobacco usage. Especially in the country like Taiwan where betel quid mostly do not contain tobacco, AN can be correlated with the increased incidence of cancer. There are different studies in the literature about AN and oral cancer but none of them have concluded with the definite pathway for carcinogenesis. The present paper includes reviews of the literature for AN and oral cancer and summarizes the possible mechanisms associated with AN-induced carcinogenesis; and we have also tried to propose pathway of carcinogenesis. [ABSTRACT FROM AUTHOR]

In Taiwan, oral cancer is causally associated with environmental carcinogens. Survivin is an anti-apoptotic protein and is generally considered a marker of malignancy. The current study explored the combined effect of survivin gene polymorphisms and environmental carcinogens on the risk and clinico-pathological development of oral cancer. Five single-nucleotide polymorphisms (SNPs) of survivin genes from 439 male patients with oral cancer and 424 male control participants (who did not have cancer) were analyzed. The survivin −31GG, +9194 GG, and +9809 TT homozygotes exhibited higher risk for oral cancer compared with the corresponding ancestral genotype, after adjustment for related confounders. The survivin −31, +9194, and +9809 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. The distribution frequency of the −31 G: +9194 A: +9809 T haplotype was significantly higher in oral cancer patients than in control participants. These results suggest that survivin gene polymorphisms and their interactions with environmental carcinogens may increase susceptibility to oral cancer in Taiwanese men.Abbreviations: AOR, adjusted odds ratio; CI, confidence intervals; PCR, polymerase chain-reaction; SNP, single-nucleotide polymorphisms. [ABSTRACT FROM PUBLISHER]

Abstract: Oesophageal cancer remains an important public health problem worldwide. This multicentre matched case–control study examined the chewing areca nut alone, betel quid with tobacco, oral snuff (snuff dipping) and cigarette smoking as the risk factors for oesophageal squamous-cell carcinoma. We enrolled 91 cases of oesophageal squamous-cell carcinoma and 364 matched controls from three tertiary-care hospitals in Karachi, Pakistan. A structured questionnaire was used to collect the data through face-to-face interview of the participants. Multivariable conditional logistic regression model showed that after adjusting for the effect of ethnicity, ever chewed areca nut alone (adjusted matched odds ratio (mORadj)=3.7; 95% confidence interval (CI): 1.6–8.5), ever chewed betel quid with tobacco (mORadj =12.8; 95% CI: 6.3–26.2), ever practiced snuff dipping (mORadj =4.3; 95% CI: 1.6–11.7) and ever smoked cigarettes (mORadj =2.9; 95% CI: 1.4–5.9) were significantly and independently associated with oesophageal squamous-cell carcinoma status. The adjusted summary population attributable risk (PAR) percent for all four substances together was 67.0. Furthermore, despite incomplete synergy, there was manifold increase in the risk of oesophageal squamous-cell carcinoma, if the respondents ever smoked cigarettes and ever chewed betel quid with tobacco (mORadj =21.4; 95% CI: 6.3–72.4) or if they ever smoked cigarettes and ever practiced snuff dipping (mORadj =14.4; 95% CI: 2.3–91.1). The adjusted PAR (%) was higher for the dual practice of smoking cigarettes and chewing betel quid with tobacco (64.3) than the dual practice of smoking cigarettes and snuff dipping (32.2). Public awareness to curtail the addiction to these substances may result in a substantial reduction in the incidence of oesophageal squamous-cell carcinoma and related mortality in this and similar settings. [Copyright &y& Elsevier]

Abstract: Background: Betel quid is a substance that commonly used among male labor in Taiwan, and the dependence potential has been reported in some studies, but no instrument has been developed specifically to assess areca/betel quid dependence. Objective: To develop a reliable and valid research instrument/screening tool for the measurement of betel quid dependence. Methods: There were 223 male prisoners with a history of betel quid chewing behavior before they were incarcerated in Kaohsiung Prison enrolled in this study. The items of the Betel Quid Dependence Scale (BQDS) were developed by the authors and were designed referring to previous research findings and the diagnostic criteria of Substance Dependence in DSM-IV. Results: The BQDS has high internal consistency (Cronbach''s α =0.921), and a three-factor structure consisting of “physical and psychological urgent need,” “increasing dose” and “maladaptive use,” which accounted for 61.2% of the total variance. There were 94 (42.2%) male-prisoners who satisfied DSM-IV criteria for dependent use, and the receiver operating characteristic (ROC) curve showed that the BQDS had an optimal cut-off score of 4, the optimal sensitivity was 0.926 and the specificity was 0.977, with the predictive accuracy up to 99.3%. Conclusions: The BQDS has good internal consistency and construct validity, and was proved to have optimal reliability and criterion validity in this special sample. Further investigation is suggested in different samples such as the general population or oral submucous fibrosis (OSF) patients to test the generalization of this instrument. [Copyright &y& Elsevier]

Abstract: Background: We aimed to evaluate the effectiveness of an oral cavity cancer visual screening program conducted in a tertiary academic medical center. We also wanted to determine which group of participants was at greater risk of contracting oral cavity cancer. Methods: Participants were first asked to relate their personal habits during the past 6 months. Visual screening of the oral cavity was then performed under adequate lighting and with proper instruments. Results: From March 2005 to January 2010, 13,878 participants were enrolled in this study. The average age was 54.6 years. Positive lesions were identified in 726 participants (5.2%), and 282 of those participants (2.1%) had oral cavity cancers confirmed. The sensitivity and specificity of this study were 98.9% and 98.7%, respectively. Those participants who were habitual smokers, alcohol consumers, and betel quid chewers had the highest risk of developing oral cavity cancer when compared with those who did not have these habits (odds ratio=46.90, 95% confidence interval=33.15–66.35, p <0.001). Conclusion: The oral screening program conducted in a tertiary medical center was effective. We suggest that individuals aged ≥40 years or who are habitual cigarette smokers, alcohol consumers, and betel quid chewers should receive oral screening regularly so that potential oral cancer can be detected as early as possible. [Copyright &y& Elsevier]

The purpose of this study was to determine the prevalence of oral soft tissue lesions in patients who attended the outpatient department, at Bharati Vidyapeeth Deemed University Dental College during a period of 18 months in 2009-2010. About 24,422 subjects belonging to a semi-urban district of Sangli in Western Maharastra (India) were screened. Out of these about 623 cases showed soft tissue lesions. Statistical analysis was done using the SPSS software. 2.5% of the population studied had one or more oral lesions associated with prosthetic use, trauma and tobacco consumption etc. Six hundred and twenty-three patients were found to have significant mucosal lesions. 75 had leukoplakia, 152 had oral submucous fibrosis, 14 had both both leukoplakia and oral submucous fibrosis, 82 had oral squamous cell carcinoma, 35 had oral lichen planus, 195 had apthous ulcers, 23 had denture stomatitis, 28 had fibroma and 19 cases had pyogenic granuloma. The findings in the present study reveal a high prevalence of oral soft tissue lesions and a rampant misuse of variety of addictive substances in the community. Close follow up and systematic evaluation is required in this population. There is an urgent need for awareness programs involving the community health workers, dentists and allied medical professionals. [ABSTRACT FROM AUTHOR]

Oral Diseases (2011) 17, 636-641 Objectives: To investigate the age-standardized incidence, demography, recent trends and patterns of incidence of oral cancer in Sri Lanka between 1985 and 2005. Materials and methods: Data on oral and oropharyngeal cancers were obtained from the published hospital-based cancer registry reports in the years 1985, 1990, 1995, 2000, and 2005. The data were analyzed by gender, age (<40 or >40 years), and by site. A linear regression analysis was performed on the age-standardized oral and oropharyngeal cancer incidence rates to examine the trends over a 20-year period. Results: There was a steady decline in the age-standardized incidence of lip and oral cavity cancers over the past 20 years in both men and women. A significant reduction of 1.9% per year is noted over this period. Contrary to this, cancers of the oropharynx (C09, C10, and C14) showed a slight increase over the same period. Conclusions: Reversal of betel quid use and smoking must be considered in accounting for declining trends for oral cancer. Increasing rates of oropharyngeal cancer raises the issue whether risk factors for the oropharynx are different to those of the oral cavity, and this may need further investigation. [ABSTRACT FROM AUTHOR]