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Activation of PI3K/Akt/NF-kB Signaling Mediates Swedish Snus Induced Proliferation and Apoptosis Evasion in the Rat Forestomach: Modulation by Blueberry.

https://arctichealth.org/en/permalink/ahliterature308291
Source
Anticancer Agents Med Chem. 2020; 20(1):59-69
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
2020
Author
Singaraj Ranjani
Jaganathan Kowshik
Josephraj Sophia
Ramesh Nivetha
Abdul B Baba
Veeran Veeravarmal
Gordana Joksic
Lars E Rutqvist
Robert Nilsson
Siddavaram Nagini
Author Affiliation
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Source
Anticancer Agents Med Chem. 2020; 20(1):59-69
Date
2020
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Animals
Apoptosis - drug effects
Blueberry Plants - chemistry
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Male
NF-kappa B - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Protective Agents - chemistry - pharmacology
Proto-Oncogene Proteins c-akt - metabolism
Rats
Rats, Wistar
Signal Transduction - drug effects
Stomach - drug effects
Structure-Activity Relationship
Sweden
Tobacco, Smokeless - adverse effects
Abstract
The present study was undertaken to ascertain whether the modulatory effects of blueberries on cell proliferation induced by Swedish snus in the rat forestomach epithelium is mediated via abrogation of the PI3K/Akt/NF?B signaling axis that regulates cell fate decision.
The transcript and protein expression of genes involved in cell cycle progression and apoptosis, as well as canonical PI3K/Akt/NF-?B signaling pathways, were analyzed by qRT-PCR, immunoblotting and ELISA. Expression profiling of noncoding RNAs (ncRNAs) that influence PI3K/Akt/NF-?B signaling was undertaken. TUNEL assay was performed using flow cytometry.
Administration of snus induced basal cell hyperplasia in the rat forestomach with increased cell proliferation and inhibition of apoptosis. This was associated with the activation of PI3K/Akt/NF?B signaling. Coadministration of blueberries significantly suppressed snus-induced hyperplasia. Analysis of the molecular mechanisms revealed that blueberries suppress the phosphorylation of Akt, NF-?B and IKKß, prevent nuclear translocation of NF-?B and modulate the expression of microRNAs that influence PI3K/Akt/NF-?B signaling.
Taken together, the results of the current study provide compelling evidence that blueberries exert significant protective effects against snus-induced soft tissue changes in the rat forestomach epithelium mediated by inhibiting key molecular players in the PI3K/Akt/NF-?B signaling axis. Long-term studies on the impact of snus exposure on various cellular processes, signaling pathways, and the interplay between genetic and epigenetic mechanisms are however warranted. The results of this investigation may contribute to the development of protection against soft tissue changes induced by smokeless tobacco in the human oral cavity.
PubMed ID
31696813 View in PubMed
Less detail

Acute effects on the ventricular function in Swedish snuffers: an echocardiographic study.

https://arctichealth.org/en/permalink/ahliterature127427
Source
Clin Physiol Funct Imaging. 2012 Mar;32(2):106-13
Publication Type
Article
Date
Mar-2012
Author
D. Sundström
M. Waldenborg
K. Emilsson
Author Affiliation
Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden. daniel.sundstrom@orebroll.se
Source
Clin Physiol Funct Imaging. 2012 Mar;32(2):106-13
Date
Mar-2012
Language
English
Publication Type
Article
Keywords
Adult
Analysis of Variance
Blood pressure
Diastole
Echocardiography, Doppler
Echocardiography, Doppler, Color
Echocardiography, Doppler, Pulsed
Female
Heart rate
Humans
Male
Middle Aged
Predictive value of tests
Stroke Volume
Sweden
Systole
Time Factors
Tobacco, Smokeless - adverse effects
Ventricular Dysfunction, Left - etiology - physiopathology - ultrasonography
Ventricular Dysfunction, Right - etiology - physiopathology - ultrasonography
Ventricular Function, Left
Ventricular Function, Right
Young Adult
Abstract
Cigarettes and Swedish snuff contain nicotine, which influence the cardiovascular system. Cigarette smoke has been shown to give an acute impairment in diastolic heart parameters. The systolic and diastolic heart function in snuff users is not thoroughly enough investigated. The aim of this study was to investigate if Swedish snuff will give an acute decrease in systolic and diastolic heart parameters in the left and right ventricles in healthy Swedish snuffers.
Thirty healthy volunteers were examined with echocardiography. The study involved recordings from four different times: before snuff intake, 5 and 30 min after intake and finally 30 min after snuff withdrawal. The systolic and diastolic heart parameters were collected with conventional echocardiographic methods. In addition, the heart frequency and blood pressure response were measured. The pulse and blood pressure response were significantly altered (P
PubMed ID
22296630 View in PubMed
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Adverse effects of Sudanese toombak vs. Swedish snuff on human oral cells.

https://arctichealth.org/en/permalink/ahliterature98857
Source
J Oral Pathol Med. 2010 Feb;39(2):128-40
Publication Type
Article
Date
Feb-2010
Author
Daniela Elena Costea
Ochiba Lukandu
Linh Bui
Muna Jaffar M Ibrahim
Raymond Lygre
Evelyn Neppelberg
Salah Osman Ibrahim
Olav Karsten Vintermyr
Anne Christine Johannessen
Author Affiliation
Section of Pathology, The Gade Institute, University of Bergen, Bergen, Norway. daniela.costea@gades.uib.no
Source
J Oral Pathol Med. 2010 Feb;39(2):128-40
Date
Feb-2010
Language
English
Publication Type
Article
Keywords
Adult
Annexin A5 - analysis
Apoptosis - drug effects
Cell Count
Cell Division - drug effects
Cell Line
Cell Proliferation - drug effects
Cell Shape - drug effects
Cell Survival - drug effects
Cells, Cultured
Coloring Agents - diagnostic use
DNA Breaks, Double-Stranded
Fibroblasts - cytology - drug effects
G2 Phase - drug effects
Humans
Keratinocytes - cytology - drug effects
Microscopy, Electron, Transmission
Mouth Mucosa - cytology - drug effects
Phosphatidylserines - analysis
Plant Extracts - adverse effects
Sudan
Sweden
Tobacco, Smokeless - adverse effects
Abstract
BACKGROUND: The high incidence of oral cancer in Sudan has been associated with the use of toombak, the local type of smokeless tobacco. However, its specific effects on human oral cells are not known. We aimed to investigate the effects of toombak on primary normal human oral keratinocytes, fibroblasts, and a dysplastic oral keratinocytic cell line, and to compare them with the effects induced by Swedish snuff. METHOD: Aqueous extracts were prepared from moist toombak and Swedish snuff and added in serial dilutions on in vitro monolayer cultured cells. Cell viability, morphology and growth, DNA double-strand breaks (gammaH2AX staining), expression of phosphatidylserine (Annexin V staining), and cell cycle were assessed after various exposure time periods. RESULTS: Significant decrease in cell number, occurrence of DNA double-strain breaks, morphological and biochemical signs of programmed cell death were detected in all oral cell types exposed to clinically relevant dilutions of toombak extract, although to a lesser extent in normal oral fibroblasts and dysplastic keratinocytes. G2/M-block was also detected in normal oral keratinocytes and fibroblasts exposed to clinically relevant dilutions of toombak extract. Swedish snuff extract had less adverse effects on oral cells, mainly at non-clinically relevant dilutions. CONCLUSION: This study indicates a potential for toombak, higher than for Swedish snuff, to damage human oral epithelium. Dysplastic oral keratinocytes were less sensitive than their normal counterparts, suggesting that they might have acquired a partially resistant phenotype to toombak-induced cytotoxic effects while still being prone to DNA damage that could lead to further malignant progression.
PubMed ID
19804503 View in PubMed
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[Adverse effects of Swedish smokeless tobacco "snus"].

https://arctichealth.org/en/permalink/ahliterature123183
Source
Duodecim. 2012;128(10):1089-96
Publication Type
Article
Date
2012
Author
Seppo Wickholm
Aira Lahtinen
Anja Ainamo
Matti Rautalahti
Author Affiliation
Johnson & Johnson Consumer Nordic, Karolinska Institutet, hammaslääketieteen osasto, parodontologia, PL 4064, SE-141 04 Huddinge, Sverige.
Source
Duodecim. 2012;128(10):1089-96
Date
2012
Language
Finnish
Publication Type
Article
Keywords
Apnea - chemically induced
Cardiovascular Diseases - chemically induced
Female
Finland
Humans
Infant, Newborn
Male
Mouth Diseases - chemically induced
Neoplasms - chemically induced
Nicotine - administration & dosage
Pre-Eclampsia - chemically induced
Pregnancy
Premature Birth - chemically induced
Risk factors
Sweden
Tobacco Use Disorder
Tobacco, Smokeless - adverse effects
Abstract
Selling smokeless tobacco (snus) in Finland is illegal, yet one-third of all males aged 16 to 18 years have tried it. A regular snus user can receive a daily dose of 60 to 150 milligrams of nicotine and become heavily addicted. The first--and easily detectable--lesions appear in the oral mucosa and gingiva. Long-time followup studies of snus use from a young age are, however, still lacking. Evidence exists of increased risk for fatal cardiovascular diseases and increased risk for injuries. Risk for oral cancer is debated, with more studies showing an increased risk than showing no risk; risk also exists for cancer of esophagus, stomach and pancreas. A new and alarming finding among female users is increased risk for preterm birth, preeclampsia and neonatal apnea.
PubMed ID
22724324 View in PubMed
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Adverse pregnancy outcomes in snuff users.

https://arctichealth.org/en/permalink/ahliterature58354
Source
Am J Obstet Gynecol. 2003 Oct;189(4):939-43
Publication Type
Article
Date
Oct-2003
Author
Lucinda J England
Richard J Levine
James L Mills
Mark A Klebanoff
Kai F Yu
Sven Cnattingius
Author Affiliation
Division of Epidemiology, Statistics, and Prevention Research, Department of Health and Human Services, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. englandl@mail.nih.gov
Source
Am J Obstet Gynecol. 2003 Oct;189(4):939-43
Date
Oct-2003
Language
English
Publication Type
Article
Keywords
Birth weight
Comparative Study
Female
Humans
Obstetric Labor, Premature - epidemiology
Pre-Eclampsia - epidemiology
Pregnancy
Pregnancy outcome
Research Support, U.S. Gov't, P.H.S.
Risk factors
Smoking - adverse effects
Tobacco, Smokeless - adverse effects
Abstract
OBJECTIVE: The purpose of the study was to evaluate the effects of smokeless tobacco use during pregnancy. STUDY DESIGN: We examined birth weight, preterm delivery, and preeclampsia in women who were delivered of singleton, live-born infants in Sweden from 1999 through 2000. For each snuff user, 10 cigarette smokers and 10 tobacco nonusers were selected randomly. RESULTS: After exclusions, 789 snuff users, 11,240 smokers, and 11,495 nonusers remained. Compared with nonusers, adjusted mean birth weight was reduced in snuff users by 39 g (95% CI, 6-72 g) and in smokers by 190 g (95% CI, 178-202 g). Preterm delivery was increased in snuff users and smokers (adjusted odds ratios, 1.98 [95% CI, 1.46-2.68] and 1.57 [95% CI, 1.38-1.80], respectively). Preeclampsia was reduced in smokers (adjusted odds ratio, 0.63; 95% CI, 0.53-0.75) but increased in snuff users (adjusted odds ratio, 1.58; 95% CI, 1.09-2.27). CONCLUSION: Snuff use was associated with increased risk of preterm delivery and preeclampsia. Snuff does not appear to be a safe alternative to cigarettes during pregnancy.
PubMed ID
14586330 View in PubMed
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An investigation on the use of snus and its association with respiratory and sleep-related symptoms: a cross-sectional population study.

https://arctichealth.org/en/permalink/ahliterature291181
Source
BMJ Open. 2017 May 29; 7(5):e015486
Publication Type
Journal Article
Date
May-29-2017
Author
Arna Ýr Gudnadóttir
Inga Sif Ólafsdóttir
Roelinde Middelveld
Linda Ekerljung
Bertil Forsberg
Karl Franklin
Eva Lindberg
Christer Janson
Author Affiliation
Deparment of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
Source
BMJ Open. 2017 May 29; 7(5):e015486
Date
May-29-2017
Language
English
Publication Type
Journal Article
Keywords
Adolescent
Adult
Age Distribution
Aged
Asthma - epidemiology - etiology
Cross-Sectional Studies
Female
Humans
Logistic Models
Male
Middle Aged
Risk factors
Sex Distribution
Sleep Wake Disorders - epidemiology - etiology
Smoking
Snoring - epidemiology - etiology
Surveys and Questionnaires
Sweden - epidemiology
Tobacco Use Disorder - epidemiology
Tobacco, Smokeless - adverse effects
Young Adult
Abstract
Studies of the health effects of moist oral tobacco, snus, have produced inconsistent results. The main objective of this study is to examine the health effects of snus use on asthma, respiratory symptoms and sleep-related problems, a field that has not been investigated before.
This cross-sectional study was based on a postal questionnaire completed by 26?697 (59.3%) participants aged 16 to 75 years and living in Sweden. The questionnaire included questions on tobacco use, asthma, respiratory symptoms and sleeping problems. The association of snus use with asthma, respiratory symptoms and sleep-related symptoms was mainly tested in never-smokers (n=16?082).
The current use of snus in never-smokers was associated with an increased risk of asthma (OR 1.51 (95%?CI 1.28 to 1.77)), asthmatic symptoms, chronic bronchitis and chronic rhinosinusitis. This association was not present among ex-snus users. Snoring was independently related to both the former and current use of snus ((OR 1.37 (95%?CI 1.12 to 1.68)) and (OR 1.59 (95%?CI 1.34 to 1.89), respectively)). A higher risk of difficulty inducing sleep was seen among snus users.
Snus use was associated with a higher prevalence of asthma, respiratory symptoms and snoring. Healthcare professionals should be aware of these possible adverse effects of snus use.
Notes
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PubMed ID
28554933 View in PubMed
Less detail

Apoptosis and expression of Bax and Bcl-2 in snuff- and non-snuff associated oral squamous cell carcinomas.

https://arctichealth.org/en/permalink/ahliterature10343
Source
Anticancer Res. 2000 Sep-Oct;20(5A):2855-60
Publication Type
Article
Author
L L Loro
O K Vintermyr
S O Ibrahim
A M Idris
A C Johannessen
Author Affiliation
Department of Odontology-Oral Pathology and Forensic Odontology, Gade Institute, Haukeland Hospital, University of Bergen, Norway. lado.loro@gades.uib.no
Source
Anticancer Res. 2000 Sep-Oct;20(5A):2855-60
Language
English
Publication Type
Article
Keywords
Apoptosis
Carcinoma, Squamous Cell - genetics - metabolism - pathology
Humans
Ki-67 Antigen - biosynthesis
Mouth Neoplasms - etiology - genetics - metabolism - pathology
Norway
Plants, Toxic
Proto-Oncogene Proteins - biosynthesis
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Research Support, Non-U.S. Gov't
Sudan
Tobacco, Smokeless - adverse effects
Tumor Suppressor Protein p53 - genetics
bcl-2-Associated X Protein
Abstract
BACKGROUND: Oral squamous cell carcinoma (OSCC) is etiologically linked to tobacco and alcohol consumption. A higher frequency of p53 gene mutations was reported in snuff (toombak)-associated OSCC from the Sudan versus those from non-users (Ibrahim et al., 1999, 10). MATERIALS AND METHODS: OSCC from Sudanese toombak users (n = 13) and non-users from the Sudan (n = 6) and Norway (n = 24) were analysed for bax, bcl-2 and Ki-67 immunohistochemically. Apoptosis was evaluated by the TUNEL method. The OSCC from the Sudan had previously been studied for p53 gene mutations. RESULTS: We found a higher apoptotic rate and a higher bax expression in OSCC from Norway compared with those from the Sudan (p
PubMed ID
11062693 View in PubMed
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The appeal of smokeless tobacco products among young Canadian smokers: the impact of pictorial health warnings and relative risk messages.

https://arctichealth.org/en/permalink/ahliterature136648
Source
Nicotine Tob Res. 2011 May;13(5):373-83
Publication Type
Article
Date
May-2011
Author
William E Callery
David Hammond
Richard J O'Connor
Geoffrey T Fong
Author Affiliation
Department of Health Studies and Gerontology, University of Waterloo, 200 University Ave. W, Waterloo, Ontario, Canada N2L 3G1.
Source
Nicotine Tob Res. 2011 May;13(5):373-83
Date
May-2011
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Audiovisual Aids
Canada
Data Collection
Health Knowledge, Attitudes, Practice
Health Promotion - methods
Humans
Product Labeling
Smoking - adverse effects - prevention & control
Smoking Cessation - methods
Social Perception
Tobacco, Smokeless - adverse effects
Young Adult
Abstract
Although the health risks from smokeless tobacco (ST) are lower than cigarettes, it remains unclear how smokers might use ST products, including as a substitute, a cessation aid, or concurrently with cigarette use, if at all. Additionally, there is little evidence examining the impact of health warning labels (HWL) on ST use and perceptions.
The current study investigated perceptions of ST products with and without HWL and a relative health risk (RHR) message. The study consisted of a full-factorial "between-subjects" experiment in which 3 HWL and a RHR message were systematically varied. Canadian smokers aged 18-30 years (N = 611) completed an online survey where they viewed four brands of ST packages altered according to the experimental conditions.
Approximately half of the smokers indicated that they were willing to try ST as a substitute and to help quit smoking. More than one quarter (28%) of smokers were unaware that using ST is less harmful than smoking. Pictorial HWL increased false beliefs about the RHR of ST and decreased smokers' willingness to try ST, whereas text warnings did not. Adding a RHR message communicating the lower risk of ST compared with cigarettes increased willingness to try ST when added to text HWL but decreased willingness to try ST even further when added to pictorial HWL.
The findings indicate relatively high levels of appeal for ST among young adult Canadian cigarette smokers. Pictorial HWL reduced the appeal of ST products and increased perceived risks, including the false belief that ST is equally harmful as cigarettes. Further research could consider evaluating designs of HWL on ST products that better balance absolute and RHR.
PubMed ID
21357730 View in PubMed
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Assessing the effect of public health information by incentivised risk estimation: An example on Swedish snus.

https://arctichealth.org/en/permalink/ahliterature299929
Source
Int J Drug Policy. 2018 04; 54:51-57
Publication Type
Journal Article
Date
04-2018
Author
Daniel Bergsvik
Ole Rogeberg
Author Affiliation
Norwegian Institute of Public Health, Department of Drug Policy, PO Box 4404, Nydalen, 0403 Oslo, Norway; Ragnar Frisch Centre for Economic Research, Gaustadalléen 21, 0349 Oslo, Norway. Electronic address: daniel.bergsvik@fhi.no.
Source
Int J Drug Policy. 2018 04; 54:51-57
Date
04-2018
Language
English
Publication Type
Journal Article
Keywords
Cigarette Smoking - adverse effects
Female
Health education
Humans
Male
Program Evaluation - methods
Reward
Risk Assessment - methods
Sweden
Tobacco, Smokeless - adverse effects
Abstract
The provision of accurate information on health damaging behaviours and products is a widely accepted and widespread governmental task. It is easily mismanaged. This study demonstrates a simple method which can help to evaluate whether such information corrects recipient risk beliefs.
Participants assess risks numerically, before and after being exposed to a relevant risk communication. Accuracy is incentivised by awarding financial prizes to answers closest to a pursued risk belief. To illustrate this method, 228 students from the University of Oslo, Norway, were asked to estimate the mortality risk of Swedish snus and cigarettes twice, before and after being exposed to one of three risk communications with information on the health dangers of snus.
The data allow us to measure how participants updated their risk beliefs after being exposed to different risk communications. Risk information from the government strongly distorted risk perceptions for snus. A newspaper article discussing the relative risks of cigarettes and snus reduced belief errors regarding snus risks, but increased belief errors regarding smoking. The perceived quality of the risk communication was not associated with decreased belief errors.
Public health information can potentially make the public less informed on risks about harmful products or behaviours. This risk can be reduced by targeting identified, measurable belief errors and empirically assessing how alternative communications affect these. The proposed method of incentivised risk estimation might be helpful in future assessments of risk communications.
PubMed ID
29414485 View in PubMed
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Assessment of a 72-hour repeated exposure to Swedish snus extract and total particulate matter from 3R4F cigarette smoke on gingival organotypic cultures.

https://arctichealth.org/en/permalink/ahliterature299104
Source
Food Chem Toxicol. 2019 Mar; 125:252-270
Publication Type
Journal Article
Date
Mar-2019
Author
Filippo Zanetti
Alain Sewer
Bjoern Titz
Walter K Schlage
Anita R Iskandar
Athanasios Kondylis
Patrice Leroy
Emmanuel Guedj
Keyur Trivedi
Ashraf Elamin
Florian Martin
Stefan Frentzel
Nikolai V Ivanov
Manuel C Peitsch
Julia Hoeng
Author Affiliation
PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland. Electronic address: filippo.zanetti@pmi.com.
Source
Food Chem Toxicol. 2019 Mar; 125:252-270
Date
Mar-2019
Language
English
Publication Type
Journal Article
Keywords
Cells, Cultured
Gingiva - drug effects - pathology
Humans
Inflammation - genetics - metabolism
Inflammation Mediators - metabolism
Male
MicroRNAs - metabolism
Middle Aged
Nicotine - analysis
Particulate Matter - analysis
Plant Extracts - adverse effects - analysis - chemistry
Sweden
Time Factors
Tobacco, Smokeless - adverse effects - analysis
Transcriptome - drug effects
Abstract
Swedish snus is a smokeless tobacco product that contains reduced levels of harmful compounds compared with cigarette smoke. In Sweden, where snus use exceeds smoking among men, relatively low rates of major smoking-related diseases have been recorded. To better understand how snus use could align with current tobacco harm reduction strategies, its potential mechanisms of toxicity must be investigated. This study aimed to determine, via a systems toxicology approach, the biological impact of repeated 72-hour exposure of human gingival epithelial organotypic cultures to extracts from both a commercial and a reference snus and the total particulate matter (TPM) from cigarette smoke. At concentrations relevant for human use, cultures treated with snus extracts induced mild, generally reversible biological changes, while TPM treatment induced substantial morphological and inflammatory alterations. Network enrichment analysis and integrative analysis of the global mRNA and miRNA expression profiles indicated a limited and mostly transient impact of the snus extracts, in particular on xenobiotic metabolism, while the effects of TPM were marked and sustained over time. High-confidence miRNAs that might be related to pathological conditions in vivo were identified. This study highlights the limited biological impact of Swedish snus extract on human organotypic gingival cultures.
PubMed ID
30610935 View in PubMed
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156 records – page 1 of 16.