An Insight into Survivin in Relevance to Hematological, Biochemical and Genetic Characteristics in Tobacco Chewers with Oral Squamous Cell Carcinoma.

BACKGROUND: Survivin is an inhibitor of apoptosis protein (IAP), encoded by the Baculoviral IAP Repeat Containing 5 (BIRC5) gene located on q arm (25.3) on chromosome 17. It is expressed in various human cancers and involved in tumor resistance to radiation and chemotherapy. The genetic analysis of the BIRC5 gene and its protein survivin levels in buccal tissue related to oral squamous cell carcinoma (OSCC) in South Indian tobacco chewers has not been studied. Hence, the study was designed to quantify survivin in buccal tissue and its association with pretreatment hematological parameters and to analyze the BIRC5 gene sequence. METHOD: In a single centric case control study, buccal tissue survivin levels were measured by ELISA. A total of 189 study subjects were categorized into Group 1 (n = 63) habitual tobacco chewers with OSCC, Group 2 (n = 63) habitual tobacco chewers without OSCC, and Group 3 (n = 63) healthy subjects as control. Retrospective hematological data were collected from Group 1 subjects and statistically analyzed. The BIRC5 gene was sequenced and data were analyzed using a bioinformatics tool. RESULTS: Survivin protein mean ± SD in Group 1 was (1670.9 ± 796.21 pg/mL), in Group 2 it was (1096.02 ± 346.17 pg/mL), and in Group 3 it was (397.5 ± 96.1 pg/mL) with significance (p < 0.001). Survivin levels showed significance with cut-off levels of absolute monocyte count (AMC), neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR) at (p = 0.001). The unique variants found only in OSCC patients were T → G in the promoter region, G → C in exon 3, C → A, A → G, G → T, T → G, A → C, G → A in exon 4, C → A, G → T, G → C in the exon 5 region. CONCLUSIONS: The tissue survivin level increased in OSCC patients compared to controls; pretreatment AMC, LMR, and NLR may serve as add-on markers along with survivin to measure the progression of OSCC. Unique mutations in the promoter and exons 3-5 were observed in sequence analysis and were associated with survivin concentrations.

Molecular and neuronal mechanisms underlying the effects of adolescent nicotine exposure on anxiety and mood disorders.

Tobacco addiction is highly co-morbid with a variety of mental health conditions, including schizophrenia, mood and anxiety disorders. Nicotine, the primary psychoactive compound in tobacco-related products is known to functionally modulate brain circuits that are disturbed in these disorders. Nicotine can potently regulate the transmission of various neurochemicals, including dopamine (DA), γ-amino-butyric acid (GABA) and glutamate, within various mesocorticolimbic structures, such as the ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex (PFC), all of which show pathologies in these disorders. Many neuropsychiatric diseases have etiological origins during neurodevelopment, typically occurring during vulnerable periods of adolescent or pre-natal brain development. During these neurodevelopmental periods, exposure to extrinsic drug insults can induce enduring and long-term pathophysiological sequelae that ultimately increase the risk of developing chronic mental health disorders in later life. These vulnerability factors are of growing concern given rising rates of adolescent nicotine exposure via traditional tobacco use and the increasing use of alternative nicotine delivery formats such as vaping and e-cigarettes. A large body of clinical and pre-clinical evidence points to an important role for adolescent exposure to nicotine and increased vulnerability to developing mood and anxiety disorders in later life. This review will examine current clinical and pre-clinical evidence that pinpoints specific mechanisms within the mesocorticolimbic circuitry and molecular biomarkers linked to the association between adolescent nicotine exposure and increased risk of developing mood and anxiety-related disorders. This article is part of the special issue on 'Vulnerabilities to Substance Abuse'.

Usefulness of salivary sialic acid as a tumor marker in tobacco chewers with oral cancer.

AIM: This study aims to assess the usefulness of salivary sialic acid (SA) as a tumor marker in the detection of oral squamous cell carcinoma (OSCC) among tobacco chewers. MATERIALS AND METHODS: After the approval of study protocol by the Institutional Ethics Committee and informed voluntary consent, salivary samples were collected from 96 participants in each group of tobacco chewers with OSCC, tobacco chewers without precancerous or cancerous lesion, and healthy controls. Salivary protein-bound SA (PBSA) and salivary-free SA (FSA) were measured by Yao et al.'s method of acid ninhydrin reaction, and the data were subjected to appropriate statistical analysis. RESULTS: The salivary PBSA and FSA levels in the Groups 1, 2, and 3 participants were 31.17 ± 7.6 mg/dL and 63.45 ± 9.8 mg/dL, 25.45 ± 16.61 mg/dL and 33.18 ± 11.38 mg/dL, and 22.73 ± 3.01 mg/dL and 21.62 ± 8.86 mg/dL, respectively. Salivary FSA levels were significantly increased among the tobacco chewers with OSCC patients (Group 1) and tobacco chewers with no premalignant lesions of the oral cavity (Group 2) compared to the healthy controls (Group 3) with P < 0.05 being statistically significant. Salivary FSA levels were significantly increased in Group 1 as compared with Group 2. The salivary PBSA was high among Group 1 as compared to the control Group 3; there was however no significant difference in the levels of salivary PBSA between Group 1 and Group 2. There was no significant difference in the PBSA levels between OSCC patients of Group 1 and the tobacco chewers without precancerous or cancerous lesion in the oral cavity of Group 2. CONCLUSION: Salivary PBSA and FSA are significantly raised in both tobacco chewers with OSCC and in tobacco chewers with no precancerous or cancerous lesions in the oral cavity. SA should therefore be used cautiously while considering it as a marker for the early detection of oral cancer. Tobacco can be a crucial confounding factor when SA is used as a biomarker in OSCC since their levels are elevated to some extent even in tobacco chewers without any clinically obvious precancerous or cancerous lesions in the oral cavity.

Epigenome-Wide Tobacco-Related Methylation Signature Identification and Their Multilevel Regulatory Network Inference for Lung Adenocarcinoma.

Tobacco exposure is one of the major risks for the initiation and progress of lung cancer. The exact corresponding mechanisms, however, are mainly unknown. Recently, a growing body of evidence has been collected supporting the involvement of DNA methylation in the regulation of gene expression in cancer cells. The identification of tobacco-related signature methylation probes and the analysis of their regulatory networks at different molecular levels may be of a great help for understanding tobacco-related tumorigenesis. Three independent lung adenocarcinoma (LUAD) datasets were used to train and validate the tobacco exposure pattern classification model. A deep selecting method was proposed and used to identify methylation signature probes from hundreds of thousands of the whole epigenome probes. Then, BIMC (biweight midcorrelation coefficient) algorithm, SRC (Spearman's rank correlation) analysis, and shortest path tracing method were explored to identify associated genes at gene regulation level and protein-protein interaction level, respectively. Afterwards, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and GO (Gene Ontology) enrichment analysis were used to analyze their molecular functions and associated pathways. 105 probes were identified as tobacco-related DNA methylation signatures. They belong to 95 genes which are involved in hsa04512, hsa04151, and other important pathways. At gene regulation level, 33 genes are uncovered to be highly related to signature probes by both BIMC and SRC methods. Among them, FARSB and other eight genes were uncovered as Hub genes in the gene regulatory network. Meanwhile, the PPI network about these 33 genes showed that MAGOH, FYN, and other five genes were the most connected core genes among them. These analysis results may provide clues for a clear biological interpretation in the molecular mechanism of tumorigenesis. Moreover, the identified signature probes may serve as potential drug targets for the precision medicine of LUAD.

Glutathione S-transferasesP1 AA (105Ile) allele increases oral cancer risk, interacts strongly with c-Jun Kinase and weakly detoxifies areca-nut metabolites.

The Glutathione S-transferases (GSTs) protects cellular DNA against oxidative damage. The role of GSTP1 polymorphism (A313G; Ile105Val) as a susceptibility factor in oral cancer was evaluated in a hospital-based case-control study in North-East India, because the habit of chewing raw areca-nut (RAN) with/without tobacco is common in this region. Genetic polymorphism was investigated by genotyping 445 cases and 444 controls. Individuals with the GSTP1 AA-genotype showed association with the oral cancer (OR = 3.1, 95% CI = 2.4-4.2, p = 0.0002). Even after adjusting for age, sex and habit the AA-genotype is found to be significantly associated with oral cancer (OR = 2.4, 95% CI = 1.7-3.2, p = 0.0001). A protein-protein docking analysis demonstrated that in the GG-genotype the binding geometry between c-Jun Kinase and GSTP1 was disrupted. It was validated by immunohistochemistry in human samples, showing lower c-Jun-phosphorylation and down-regulation of pro-apoptotic genes in normal oral epithelial cells with the AA-genotype. In silico docking revealed that AA-genotype weakly detoxifies the RAN/tobacco metabolites. In addition, experiments revealed a higher level of 8-Oxo-2'-deoxyguanosine induction in tumor samples with the AA-genotype. Thus, habit of using RAN/tobacco and GSTP1 AA-genotype together play a significant role in predisposition to oral cancer risk by showing higher DNA-lesions and lower c-Jun phosphorylation that may inhibit apoptosis.

Potential Effect of Tobacco Consumption through Smoking and Chewing Tobacco on IL1beta Protein Expression in Chronic Periodontitis Patients: In Silico Molecular Docking Study.

Detrimental effect of bad oral habits, such as smoking and chewing tobacco, on chronic periodontitis (CP) manifest chronic inflammation of gingival tissues which majorly results in gum bleeding, and teeth loss. A genetic association study of Interleukin 1 beta (IL1ß) has been conducted in CP patients having smoking and chewing tobacco habits in regular life style. A molecular docking study has been consequently done to analyze the effect of tobacco on CP progression in depth. All statistical evaluation has been done by using SPSS v16.0. The findings of the study show the significant association of IL1ß gene polymorphisms with CP increased susceptibility in combination of oral habits as mentioned earlier. The docking profile has showed the highest binding affinity of IL1ß protein with the Nicotine derived Nitrosamine Ketone (NNK), one of the derivatives of nicotine which is in-taken through the habits associated with smoking and chewing tobacco. Nicotine, N-nitrosoanabasine, and N-nitrosonornicotine, the other derivatives, have also demonstrated significant impact over the IL1ß protein-caused altered expression. Thus, this study concluded that the harmful effect of tobacco may increase the inflammation in periodontia by inducing the inflammatory active site of the IL1ß protein in the CP patients.

Superoxide Dismutase response: physiological plasticity in tobacco users.

BACKGROUND: Free radicals (FRs) are active chemical substances having unpaired electron(s) which participate in the causation of precancerous lesions or cancer in tobacco habituates. Alterations in the antioxidant levels are reflected throughout the antioxidant enzyme activities in blood, wherein erythrocytes are considered highly sensitive to those enzymes. Our study was therefore aimed to assess the effects of tobacco consumption on erythrocyte antioxidant enzyme- Superoxide dismutase (E-SOD) and evaluate its defensive action. METHODS: E-SOD was estimated in 32 participants categorized in 2 groups (tobacco users and controls). 3 mL venous blood was withdrawn and antioxidant levels were assessed using RANSOD kit (Randox, Catalogue No.-125) as per the manufacturer's instructions. The E-SOD activity was then determined using spectrophotometry and the data was statistically evaluated. RESULTS: The Two-tailed Paired t-test was applied in smokers-SOD intergroup (mean=-124.45, P<0.0001) and chewers-SOD intergroup (mean=-66.70, P=0.1017). The mean SOD values (139.72±36.94) in cases were found to be significantly lower as compared to controls (212.75±37.04). The lowest SOD level was seen with chewers compared to other groups. CONCLUSIONS: E-SOD was found to be lowest among tobacco chewers probably due to the fact of excessive enzyme activity against prolonged release of carcinogens. The variability in the enzyme activity envisaged its potential as a biomarker in establishing the oral potentially malignant disorders (OPMDs) much before the lesions arises or detect the progression of existing lesion to malignancy.

Snus users had high levels of nicotine, cotinine and 3-hydroxycotinine in their breastmilk, and the clearance was slower than in smoking mothers.

AIM: Using snus, an oral moist tobacco, has increased among pregnant women in Sweden, the only European Union country where sales are legal. This study evaluated whether snus generated similar concentrations of nicotine and its metabolites in breastmilk to cigarette smoking. METHODS: We analysed 49 breastmilk samples from 33 nursing mother - 13 snus users, six cigarette smokers and 14 controls - for concentrations of nicotine, cotinine and 3-hydroxycotinine. The mothers were recruited at antenatal clinics in Sweden from 2007 to 2012. RESULTS: The median nicotine concentration in breastmilk of the snus users was 38.7 ng/mL (0-137) versus 24.0 ng/mL (0-56) in smokers, with median cotinine levels of 327.6 ng/mL (37-958) versus 164.4 ng/mL and median 3-hydroxycotinine levels of 202.7 ng/mL (28-452) versus 112.4 (0-231), respectively. Nicotine was still detected in the breastmilk of eight of the 13 snus users after abstaining from tobacco for a median duration of 11 hours (0.6-12.5), while the breastmilk of the smokers was nicotine-free after four hours' abstinence. CONCLUSION: Snus users had high levels of nicotine and metabolites in their breastmilk and nicotine was found even after 12.5 hours of abstinence.

Expression analysis of cyclooxygenase-2 in patients suffering from esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. A total of 69 diagnosed patients of ESCC, both Pakistanis and Afghans were enrolled. Various risk factors associated with ESCC were recorded. Mean age at the time of diagnosis was 55 years. Out of 69 patients of ESCC 46 (67%) were users of dipping tobacco (Naswar). Expression of COX-2 was determined in normal esophageal mucosa, CIS and invasive ESCC using Immunohistochemistry (IHC). Differences of mean were computed using ANOVA followed by applying Post Hoc test. Patients were categorized as positive with high expression or negative with low to nil expression. ANOVA showed large differences in expression of COX-2 in normal healthy mucosa compared with CIS and ESCC with the mean difference of -9.529 and -7.370 respectively, p-value being <.05 at 95% confidence interval (CI). No significant difference was noticed in the expression of COX-2 in CIS compared with ESCC with p-value >.05 at 95% CI. Our complete cohort (23-85 years) showed statistically significant difference in the expression of COX-2 gene in ESCC and CIS tissue samples compared with normal healthy mucosa. Results of this study indicate that over-expression of COX-2 is positively associated with ESCC.

Prevalencia del consumo de tabaco en el embarazo: optimización del diagnóstico / Prevalence of smoking in pregnancy: Optimization of the diagnosis

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Maternal snuff use and cotinine in late pregnancy-A validation study.

INTRODUCTION: Oral moist snuff is widely used in Sweden including during pregnancy. Maternal snuff use has been associated with increased risks of adverse pregnancy outcomes in epidemiological studies. Self-reported maternal snuff use has not been validated previously. The main objective of this study was to validate self-reported snuff use in pregnancy in a prospective cohort study and in the Medical Birth Register. MATERIAL AND METHODS: A prospective Swedish cohort study, 2005-2011, in which 572 women were asked to participate. Of 474 recruited women, 381 non-smokers (263 snuff users and 118 non-tobacco users) were included in the main analyses. Participants prospectively reported snuff use through questionnaires. Medical Birth Register data on the participants was obtained. Maternal urine cotinine was collected in late pregnancy and was used as a biomarker. RESULTS: Cotinine levels in maternal urine confirmed a high validity of self-reported snuff use through questionnaires in late pregnancy; sensitivity and specificity values were 98% and 96%, respectively. In the Medical Birth Register, 45% of the snuff users were misclassified as nonusers in late pregnancy. There were significant differences in median cotinine levels between users of mini pouches and users of standard pouches, but there was a great difference of cotinine levels among users with similar number of pouches used daily. CONCLUSIONS: Self-reported snuff use through questionnaires has high validity. In the Medical Birth Register, in late pregnancy, many snuff users were misclassified as nonusers. As a consequence, there is a risk of underestimating the harmful effects of snuff use when using late pregnancy Medical Birth Register data.

Rapid diagnostic method of tobacco products in saliva by fourier transform infrared spectroscopy (FTIR).

The present study was designed to explore the easy and fast method diagnosis of tobacco products in saliva of tobacco users (TU) by FTIR. Sixty four male tobacco users (TU) with mean age range 15.3 to 30.7 years were randomly selected for collection of saliva samples before and after tobacco use (smoking, chewing and dipping tobacco). Twenty were the smoking tobacco users (STU), 24 were chewing tobacco users (CTU) and 20 were dipping tobacco users (DTU). CTU were the users of Mainpuri (n=10) and users of PEN, FIT, 2100 (n=14). Forty eight saliva samples of age and gender matched healthy individuals with negative personal or family history of any addiction were also collected for comparison which served as controls. All were analyzed for their salivary flow rate, salivary pH and salivary diagnostic bands by FTIR. Significantly increased SFR (p<0.05) and salivary pH were found in after chewing tobacco as compared to before its chewing. The comparison between after tobacco use and controls we found decreased SFR and salivary pH for STU. Significant decreased SFR and increased salivary pH were found before or after use of dipping tobacco as compared to controls. Sharp bands at 735-745 cm-1 were found and may be used as salivary diagnostic bands for STU, 945-949 cm-1 for DTU and 900-915 cm-1 for CTU as well as DTU. In conclusion, the salivary diagnostic bands were found at 735-745 cm-1, 900-915 cm-1 and 945-949 cm-1 for TU by easy and fast method using FTIR.

Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes.

Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated. From a biological perspective, however, long-term (chronic) exposure to tobacco mimics the pathogenesis of oral cancer more closely. We developed a cell line model to investigate the chronic effects of chewing tobacco. Chronic exposure to tobacco resulted in higher cellular proliferation and invasive ability of the normal oral keratinocytes (OKF6/TERT1). We carried out quantitative proteomic analysis of OKF6/TERT1 cells chronically treated with chewing tobacco compared to the untreated cells. We identified a total of 3,636 proteins among which expression of 408 proteins were found to be significantly altered. Among the overexpressed proteins, stearoyl-CoA desaturase (SCD) was found to be 2.6-fold overexpressed in the tobacco treated cells. Silencing/inhibition of SCD using its specific siRNA or inhibitor led to a decrease in cellular proliferation, invasion and colony forming ability of not only the tobacco treated cells but also in a panel of head and neck cancer cell lines. These findings suggest that chronic exposure to chewing tobacco induced carcinogenesis in non-malignant oral epithelial cells and SCD plays an essential role in this process. The current study provides evidence that SCD can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients who are users of tobacco.

Estudio multicéntrico de normalización y estandarización de instrumentos neuropsicológicos en personas sanas para población española: metodología y características del proyecto Normacog / Multisite study for norming and standardizing neuropsychological instruments in healthy people for Spanish population: methods and characteristics of Normacog project

Introducción. Muchos de los instrumentos neuropsicológicos utilizados en España se han normalizado en población hispanohablante procedente de Estados Unidos y Sudamérica, con grupos de edad y características restrictivas. Utilizar este tipo de normas disminuye potencialmente su representatividad, la interpretación de los resultados y las decisiones clínicas. Este estudio se enmarca dentro del proyecto Normacog, con el fin de estandarizar instrumentos neuropsicológicos en una muestra representativa de la sociedad española. Objetivo. Presentar la metodología de normalización llevada a cabo en el proyecto Normacog y las características sociodemográficas de la población española y de los participantes incluidos en el estudio. Sujetos y métodos. Se reclutaron 711 participantes (rango: 18-90 años) de diferentes áreas geográficas de España, incluyendo los datos sociodemográficos, médicos, hábitos habituales, lengua materna, bilingüismo y dominancia manual. Cada participante completó 19 instrumentos que evaluaban un amplio rango de dominios cognitivos, como memoria verbal y visual, atención, funciones ejecutivas, velocidad de procesamiento o fluidez y denominación verbal. Resultados. La muestra final normativa refleja las características sociodemográficas y la representatividad de la población española de acuerdo con los rangos de edad, educación y sexo. Conclusiones. Se describe la metodología de normalización y las características de la muestra incluida en el estudio multicéntrico Normacog, mediante el cual se llevará a cabo la estandarización y normalización de instrumentos neuropsicológicos, teniendo en cuenta las características sociodemográficas propias de la población española. El proyecto Normacog proporciona datos normativos adecuados a nuestro medio cultural, y es esencial para poder realizar un diagnóstico clínico y neuropsicológico fiable (AU)

Introduction. Many neuropsychological tests used in Spain have been normed on Spanish-speaking persons in the USA and South America. In addition, the normative samples often span limited age or educational ranges, potentially decreasing their representativeness of the population, the interpretation of test results, and clinical decisions based on them. This study is part of the Normacog project which seeks to standardize neuropsychological instruments in a representative sample of Spanish society. Aim. To present the normalization methodology undertaken in the Normacog project and the sociodemographic characteristics of participants and Spanish population. Subjects and methods. Seven hundred and eleven participants aged 18-90 years were recruited from different geographical regions in Spain. Their sociodemographic characteristics, medical history, habits, native language, bilingualism and handedness were taken into account. Each participant completed 19 tests that assess a wide variety of cognitive domains such as verbal and visual memory, executive functions, processing speed or naming and verbal fluency. Results. The final normative sample mirrors the population of Spain in age, education, and sex distributions. Conclusions. This article describes the normalization methodology and the characteristics of participants included in the multicenter Normacog study. This study seeks to standardize and normalize neuropsychological instruments, taking into account the sociodemographic characteristics of Spanish population. The Normacog project will provide normative data that are appropriate to our cultural environment, and essential for using these measures to form reliable clinical and diagnostic inferences (AU)

A longitudinal proton magnetic resonance spectroscopy study investigating oxidative stress as a result of alcohol and tobacco use in youth with bipolar disorder.

Alcohol and tobacco have been suggested to be "aggravating factors" for neuroprogression in bipolar disorder (BD), however the impact of these substances on the underlying neurobiology is limited. Oxidative stress is a key target for research into neuroprogression in BD and in accordance with this model, our previous cross-sectional studies have found that risky alcohol and tobacco use in BD is associated with increased oxidative stress, investigated via in vivo glutathione (GSH) measured by proton magnetic resonance spectroscopy ((1)H-MRS) in the anterior cingulate cortex (ACC). What remains unknown is whether the negative impact on GSH levels can be modified as a result of limiting alcohol and tobacco use. Thirty BD patients were included in the study. (1)H-MRS and tobacco and alcohol measures were conducted at baseline and follow-up assessments (15.5±4.6 months apart). Pearson׳s correlations were performed between percentage change in GSH concentration and changes in alcohol/tobacco use. Regression analyses were then conducted to further explore the significant correlations. An increase in GSH was associated with a decrease in alcohol consumption (r=-0.381, p<0.05) and frequency of tobacco use (-0.367, p=0.05). Change in alcohol consumption, tobacco use and age were significant predictors of change in GSH concentration (F (3, 26)=3.69, p<0.05). Due to the high comorbidity of alcohol and tobacco use in the sample, the individual effects of these substances on GSH levels could not be determined. This study offers longitudinal evidence that changing risky drinking patterns and tobacco use early in the course of BD is associated with improvements in antioxidant capacity, and therefore may be specific targets for early intervention and prevention of neuroprogression in BD.

Scalp hair and blood cadmium levels in association with chewing gutkha, mainpuri, and snuff, among patients with oral cancer in Pakistan.

BACKGROUND: It has been reported that smokeless tobacco (SLT) chewing can lead to caners of oral cavity. In this study, the relationship between cadmium exposure via consumption of different SLT products by patients with oral cancer with related to referents belongs to different cities of Pakistan are investigated. METHODS: The cadmium in different types of SLT products (gutkha, mainpuri and snuff) consumed by studied population and biological samples (scalp hair and blood) of cancerous and healthy subjects were analyzed. Both referents and patients with cancer have same age group (ranged 30-60 years), socioeconomic status, localities, and dietary habits. The concentrations of cadmium in SLT products and biological samples were measured by electrothermal atomic absorption spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked by certified reference materials. RESULTS: It was estimated that 10 g intake of different types of gutkha, mainpuri, and snuff could contribute, 18-40%, 15.7-33.6%, and 14-68% of the provisional maximum tolerable daily intake of cadmium, respectively for adults (60 kg). The results of present study showed that the mean value of cadmium was significantly higher in scalp hair and blood samples of patients with oral cancer as compared to those results obtained for referents (P < 0.001). CONCLUSIONS: The high exposure of cadmium due to consuming different SLT products may have synergistic effects with other risk factors associated for oral cancer.

¿El consumo de cigarrillos y alcohol se relaciona con el consumo de cannabis y el juego problema en adolescentes españoles? / Do cigarette smoking and alcohol consumption associate with cannabis use and problem gambling among Spanish adolescents?

Este estudio examinó la relación entre consumo de tabaco y alcohol, y consumo de cannabis y juego problema en una muestra aleatoria y representativa de 1.447 adolescentes españoles (797 varones y 650 mujeres con una media de edad de 12,8 años). Los participantes respondieron a un cuestionario elaborado a tal efecto que recogía información acerca del consumo de cigarrillos, de alcohol (cerveza, vino y licores) y cannabis. El juego se evaluó con el South Oaks Gambling Screen Revised for Adolescents (SOGS-RA). Los resultados indicaron una asociación positiva y significativa entre el consumo de tabaco y alcohol y las dos variables analizadas. Se halló un mayor porcentaje de fumadores y consumidores de alcohol entre los que habían consumido cannabis en alguna ocasión así como entre los jugadores problema. Además, el análisis de regresión lineal múltiple mostró que tanto el consumo de cigarrillos como de alcohol (cerveza y vino) se relacionaban positivamente con el inicio en el consumo de cannabis y con una mayor implicación en el juego

This article examined the relationship between cigarette smoking or alcohol consumption and cannabis use and problem gambling among a random and representative sample of 1447 Spanish adolescents (797 males and 650 females with an average age of 12.8 years). An ad hoc questionnaire was used to assess cigarette smoking, alcohol consumption (beer, wine and spirits) and cannabis use. Gambling was assessed with the South Oaks Gambling Screen Revised for Adolescents (SOGS-RA). Results indicated a positive and significant association between cigarette smoking and alcohol consumption and the two aforementioned variables. A larger percentage of cigarette smokers and drinkers was found among those participants who had consumed cannabis before or scored significantly in problem gambling. Additionally, multiple regression analysis confirmed that both cigarette smoking and alcohol consumption (beer and wine) were the most determinant variables for cannabis use and problem gambling

Características clínicas y demográficas de bebedores "por atracones" que se relacionan con una falta de eficacia de la intervención breve y el consejo médico / Clinical and Demographic Characteristics of Binge Drinkers Associated with Lack of Efficacy of Brief Intervention and Medical Advice

La Intervención Breve (IB) y el Consejo Médico simple (CM) son intervenciones psicoterapéuticas usadas para el tratamiento del consumo de alcohol por atracones en Atención Primaria. A pesar de la frecuencia de este patrón de abuso en Europa y en los Estados Unidos, ningún estudio ha evaluado las características de los sujetos que no responden a esas dos técnicas. Objetivo:. determinar las características demográficas y clínicas de los bebedores por atracones en los que la IB y el CM no son efectivos para la reducción del consumo perjudicial de alcohol. Métodos:. Se trata de un análisis secundario de los datos obtenidos en un ensayo aleatorizado de intervención breve en alcohol con un período de seguimiento de 12 meses. Un total de 674 sujetos (89%) participaron durante todo el estudio hasta el final. La variable principal fue el cambio en el uso perjudicial de alcohol tras 12 meses de seguimiento. Resultados:. Para ambos grupos de tratamiento las variables que predecían la continuidad en el consumo perjudicial tras el seguimiento eran: bajo nivel educativo, ser jóvenes, el número de cigarrillos fumados, la historia familiar de alcoholismo y la gravedad del consumo de alcohol basalmente. Conclusiones:. Las características clínicas y sociodemográficas de los sujetos con un patrón de consumo de alcohol por atracones atendidos en Atención primaria influyen en el pronóstico de las Intervenciones breves y del Consejo Médico

Brief Counseling Intervention (BCI) and Medical advice (MA) are psychotherapeutic approaches used for the treatment of binge drinkers in Primary Care. Although binge drinking is a common pattern of alcohol misuse in Europe and in the US, no studies have evaluated those subjects who do not respond to Brief Counseling Interventions or Medical Advice. Objective: To determine the clinical and demographic characteristics of binge drinkers in whom BCI or MA are not effective in reducing harmful alcohol use. Methods: This is a secondary analysis of data from a randomized alcohol brief intervention trial with a 12-month follow-up period. A total of 674 subjects (89%) participated right through to the end of the study. The primary outcome measure was change in harmful alcohol use from baseline to 12 months. Results:. The strongest baseline predictors of harmful alcohol use during follow-up were educational status, young adults, and high number of cigarettes smoked, present family history of alcoholism, treatment condition and number of drinks per episode of binge drinking. Conclusions:. Binge drinkers are a heterogeneous group that responds to brief intervention or MA but in a subgroup of them these interventions fail to prevent harmful alcohol use. Other interventions should be implemented for these subjects

Nicotine exposure, blood pressure, and inflammation in tobacco smokers and chewers in a rural community in Nepal.

Tobacco consumption is high amongst the people of Xxx. This study was carried out in 2011 in a rural community of Xxx, to compare pathological parameters associated with tobacco use in relation to nicotine metabolism between smokers, chewers, and a control group. A total of 216 volunteers provided blood and urine samples for testing nicotine metabolites, C-reactive protein, and cell counts. Data were analyzed using ANOVA, correlation, and t-tests using STATA. Differences in blood pressure amongst the groups indicate a role of smoking in preventing a rise in BP with age, likely attributable to a different mechanism of metabolism of tobacco constituents.

Effects of tobacco constituents and psychological stress on the beta-adrenergic regulation of non-small cell lung cancer and pancreatic cancer: implications for intervention.

This review summarizes current preclinical and clinical evidence in support of the hypothesis that smoking and psychological stress have significant cancer promoting effects on non small cell lung cancer and pancreatic cancer via direct and indirect effects on nicotinic receptor-regulated beta-adrenergic signaling. Evidence is provided that targeted pharmacological interference with the resulting hyperactive cAMP-dependent signaling by beta-blockers or by γ-aminobutyric acid as well as positive psychological influences may be highly effective in preventing and improving clinical outcomes of these cancers, provided that appropriate diagnostic protocols are followed to monitor systemic levels of stress neurotransmitters and cAMP.