Browsing by Subject "Alcohol"

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  • Mustonen, Antti; Alakokkare, Anni-Emilia; Salom, Caroline; Hurtig, Tuula; Levola, Jonna; Scott, James G.; Miettunen, Jouko; Niemelä, Solja (2021)
    Objective: Early onset of alcohol use is associated with an increased risk of substance use disorders (SUD), but few studies have examined associations with other psychiatric disorders. Our aim was to study the association between the age of first alcohol intoxication (AFI) and the risk of psychiatric disorders in a Finnish general population sample. Methods: We utilized a prospective, general population-based study, the Northern Finland Birth Cohort 1986. In all, 6,290 15?16-year old adolescents answered questions on AFI and were followed up until the age of 33 years for psychiatric disorders (any psychiatric disorder, psychosis, SUD, mood disorders and anxiety disorders) by using nationwide register linkage data. Cox-regression analysis with Hazard Ratios (HR, with 95% confidence intervals (CI)) was used to assess the risk of psychiatric disorders associated with AFI. Results: Statistically significant associations were observed between AFI and any psychiatric disorder, psychosis, SUDs, and mood disorders. After adjustments for other substance use, family structure, sex and parental psychiatric disorders, AFIs of 13?14 years and
  • Lehikoinen, Anni I.; Kärkkäinen, Olli K.; Lehtonen, Marko A.S.; Auriola, Seppo O.K.; Hanhineva, Kati J.; Heinonen, Seppo T. (2018)
    Background: Although the effects of alcohol on metabolic processes in the body have been studied widely, there do not appear to be any previous reports clarifying how substance abuse changes metabolic profiles of pregnant women during the first trimester of pregnancy. Objective: Our aim was to evaluate the effect of substance abuse, especially alcohol use, on the metabolic profile of pregnant women during the first trimester. Study design: We applied mass spectrometry based non-targeted metabolite profiling of serum collected during routine visit to the hospital between gestational weeks 9 + 0 to 11 + 6 from controls (n = 55), alcohol users (n = 19), drug users (n = 24) and tobacco smokers (n = 40). Results: We observed statistically significantly differences among the study groups in serum levels of glutamate, glutamine, and serotonin (p-values Conclusion: The present study shows that alcohol and drug use were associated with increased glutamate, and decreased glutamine levels, and alcohol use is associated with decreased serotonin levels. This study serves as a proof-of-concept that the metabolite profile of human first trimester serum samples could be used to detect alcohol exposure during pregnancy. (C) 2018 Elsevier B.V. All rights reserved.
  • Dickerman, Barbra A.; Markt, Sarah Coseo; Koskenvuo, Markku; Pukkala, Eero; Mucci, Lorelei A.; Kaprio, Jaakko (2016)
    Purpose Alcohol intake may be associated with cancer risk, but epidemiologic evidence for prostate cancer is inconsistent. We aimed to prospectively investigate the association between midlife alcohol intake and drinking patterns with future prostate cancer risk and mortality in a population-based cohort of Finnish twins. Methods Data were drawn from the Older Finnish Twin Cohort and included 11,372 twins followed from 1981 to 2012. Alcohol consumption was assessed by questionnaires administered at two time points over follow-up. Over the study period, 601 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between weekly alcohol intake and binge drinking patterns with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were performed to control for potential confounding by shared genetic and early environmental factors. Results Compared to light drinkers ( Conclusion Heavy regular alcohol consumption and binge drinking patterns may be associated with increased prostate cancer risk, while abstinence may be associated with increased risk of prostate cancer-specific mortality compared to light alcohol consumption.
  • Lachenmeier, Dirk W.; Salaspuro, Mikko (2017)
    Humans are cumulatively exposed to acetaldehyde from various sources including alcoholic beverages, tobacco smoke, foods and beverages. The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract. The risk assessment has so far relied on thresholds based on animal toxicology with lower one-sided confidence limit of the benchmark dose values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day dependent on species and endpoint. The animal data is problematic for regulatory toxicology for various reasons (lack in study quality, problems in animal models and appropriateness of endpoints - especially cancer - for transfer to humans). In this study, data from genetic epidemiologic and biochemical studies are reviewed. The increase in the daily exposure dose to acetaldehyde in alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The acetaldehyde increase due to ALDH2 inactivity was calculated to be 6.7 mu g/kg bw/day for heavy drinkers, which is associated with odds ratios of up to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology based risk assessments may have underestimated the risk of acetaldehyde. Risk assessments of acetaldehyde need to be revised using this updated evidence. (C) 2017 The Authors. Published by Elsevier Inc.
  • Liskola, Joni; Haravuori, Henna; Lindberg, Nina; Niemelä, Solja; Karlsson, Linnea; Kiviruusu, Olli; Marttunen, Mauri (2018)
    Background: The Alcohol Use Disorders Identification Test (AUDIT) is commonly used in adults to screen for harmful alcohol consumption but few studies exist on its use among adolescents. Our aim was to validate the AUDIT and its derivative consumption questionnaire (AUDIT-C) as screening instruments for the detection of problem use of alcohol in adolescents. Methods: 621 adolescents (age-range, 12-19 years) were drawn from clinical and population samples who completed the AUDIT questionnaire. Psychiatric diagnoses were assessed using K-SADS-PL. A rating based on the K-SADS-PL was used to assess alcohol use habits, alcohol use disorders, screening and symptom criteria questions. Screening performance of the AUDIT and AUDIT-C sum scores and Receiver Operating Characteristic (ROC) curves were calculated. The diagnostic odds ratios (dOR) were calculated to express the overall discrimination between cut-offs. Results: Comparisons of ROC between the AUDIT and AUDIT-C pairs indicated a slightly better test performance by AUDIT for the whole sample and in a proportion of the subsamples. Optimal cut-off value for the AUDIT was >= 5 (sensitivity 0.931, specificity 0.772, dOR 45.22; 95% CI: 24.72-83.57) for detecting alcohol problem use. The corresponding optimal cut-off value for the AUDIT-C was >= 3 in detecting alcohol problem use (sensitivity 0.952, specificity 0.663, dOR 39.31; 95% CI: 19.46-78.97). Agreement between the AUDIT and AUDIT-C using these cut-off scores was high at 91.9%. Conclusions: Our results for the cut-off scores for the early detection of alcohol problem use in adolescents are >= 5 for AUDIT, and >= 3 for AUDIT-C.
  • Heikkinen, Noora; Kärkkäinen, Olli; Laukkanen, Eila; Kekkonen, Virve; Kaarre, Outi; Kivimäki, Petri; Könönen, Mervi; Velagapudi, Vidya; Nandania, Jatin; Lehto, Soili M.; Niskanen, Eini; Vanninen, Ritva; Tolmunen, Tommi (2019)
    Our aim was to analyze metabolite profile changes in serum associated with moderate-to-heavy consumption of alcohol in young adults and to evaluate whether these changes are connected to reduced brain gray matter volumes. These study population consisted of young adults with a 10-year history of moderate-to-heavy alcohol consumption (n = 35) and light-drinking controls (n = 27). We used the targeted liquid chromatography mass spectrometry method to measure concentrations of metabolites in serum, and 3.0 T magnetic resonance imaging to assess brain gray matter volumes. Alterations in amino acid and energy metabolism were observed in the moderate-to-heavy drinking young adults when compared to the controls. After correction for multiple testing, the group of moderate-to-heavy drinking young adults had increased serum concentrations of 1-methylhistamine (p = 0.001, d = 0.82) when compared to the controls. Furthermore, concentrations of 1-methylhistamine (r = 0.48, p = 0.004) and creatine (r = 0.52, p = 0.001) were negatively correlated with the brain gray matter volumes in the females. Overall, our results show association between moderate-to-heavy use of alcohol and altered metabolite profile in young adults as well as suggesting that some of these changes could be associated with the reduced brain gray matter volume. (C) 2018 Elsevier Inc. All rights reserved.
  • Virtanen, Suvi; Kuja-Halkola, Ralf; Mataix-Cols, David; Jayaram-Lindström, Nitya; D'Onofrio, Brian M.; Larsson, Henrik; Ruck, Christian; Suvisaari, Jaana; Lichtenstein, Paul; Latvala, Antti (2020)
    Background Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors. Methods We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis. Results Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse. Conclusions Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.
  • Mariottini, Claudia; Kriikku, Pirkko; Ojanperä, Ilkka (2021)
    Background: Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. Methods: All cases in the Finnish national post-mortem toxicology database from 2016-2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15-64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. Results: There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25-64 years. Conclusions: The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.
  • Airaksinen, Noora K.; Nurmi-Lüthje, Ilona S.; Kataja, J. Matti; Kröger, Heikki P. J.; Lüthje, Peter M. J. (2018)
    Background: Most of the cycling accidents that occur in Finland do not end up in the official traffic accident statistics. Thus, there is minimal information on these accidents and their consequences, particularly in cases in which alcohol was involved. The focus of the present study is on cycling accidents and injuries involving alcohol in particular. Methods: Data on patients visiting the emergency department at North Kymi Hospital because of a cycling accident was prospectively collected for two years, from June 1, 2004 to May 31, 2006. Blood alcohol concentration (BAC) was measured on admission with a breath analyser. The severity of the cycling injuries was classified according to the Abbreviated Injury Scale (AIS). Results: A total of 217 cycling accidents occurred. One third of the injured cyclists were involved with alcohol at the time of visiting the hospital. Of these, 85% were males. A blood alcohol concentration of Conclusions: Cyclists involved with alcohol were, in most cases, heavily intoxicated and were not wearing a bicycle helmet. Head injuries were more common among these cyclists than among sober cyclists. As cycling continues to increase, it is important to monitor cycling accidents, improve the accident statistics and heighten awareness of the risks of head injuries when cycling under the influence of alcohol. (c) 2018 Elsevier Ltd. All rights reserved.
  • Zhang, Christine R.; Kurniawan, Nyoman D.; Yamada, Lisa; Fleming, Whitney; Kaminen-Ahola, Nina; Ahola, Arttu; Galloway, Graham; Chong, Suyinn (2019)
    We examined whether an early-life event ethanol exposure in the initial stages of pregnancy affected offspring brain structure, energy metabolism, and body composition in later life. Consumption of 10% (v/v) ethanol by inbred C57BL/6J female mice from 0.5 to 8.5 days post coitum was used to model alcohol exposure during the first 3-4 weeks of gestation in humans, when pregnancy is not typically recognized. At adolescence (postnatal day [P] 28) and adulthood (P64), the brains of male offspring were scanned ex vivo using ultra-high field (16.4 T) magnetic resonance imaging and diffusion tensor imaging. Energy metabolism and body composition were measured in adulthood by indirect calorimetry and dual energy X-ray absorptiometry (DXA), respectively. Ethanol exposure had no substantial impact on white matter organization in the anterior commissure, corpus callosum, hippocampal commissure, internal capsule, optic tract, or thalamus. Whole brain volume and the volumes of the neocortex, cerebellum, and caudate putamen were also unaffected. Subtle, but non-significant, effects were observed on the hippocampus and the hypothalamus in adult ethanol-exposed male offspring. Ethanol exposure was additionally associated with a trend toward decreased oxygen consumption, carbon dioxide production, and reduced daily energy expenditure, as well as significantly increased adiposity, albeit with normal body weight and food intake, in adult male offspring. In summary, ethanol exposure restricted to early gestation had subtle long-term effects on the structure of specific brain regions in male offspring. The sensitivity of the hippocampus to ethanol-induced damage is reminiscent of that reported by other studies despite differences in the level, timing, and duration of exposure and likely contributes to the cognitive impairment that characteristically results from prenatal ethanol exposure. The hypothalamus plays an important role in regulating metabolism and energy homeostasis. Our finding of altered daily energy expenditure and adiposity in adult ethanol-exposed males is consistent with the idea that central nervous system abnormalities also underpin some of the metabolic phenotypes associated with ethanol exposure in pregnancy. (C) 2018 Elsevier Inc. All rights reserved.
  • Pajunen, T.; Vuori, E.; Lunetta, P. (2018)
    Background: Post-mortem (PM) ethanol production may hamper the interpretation of blood alcohol concentration (BAC) in victims of drowning. Different exclusion criteria (e.g. cases with low BAC or with protracted interval between death and toxicological analysis) have been proposed with no factual figures to reduce the potential bias due to PM ethanol production when examining the prevalence rates for alcohol-related drowning. The aim of this study is to verify the extent to which PM alcohol production may affect the accuracy of studies on drowning and alcohol. Findings: Unintentional fatal drowning cases (n = 967) for which a full medico-legal autopsy and toxicological analysis was performed, in Finland, from 2000 to 2013, and relevant variables (demographic data of the victims, month of incident, PM submersion time, blood alcohol concentration, urine alcohol concentration (UAC), vitreous humour alcohol concentration (VAC) were available. Overall, out of 967 unintentional drownings, 623 (64.4%) were positive for alcohol (BAC > 0 mg/dL), 595 (61.5%) had a BAC ≥ 50 mg/dL, and 567 (58.6%) a BAC ≥ 100 mg/dL. Simultaneous measurements, in each victim, of BAC, UAC, and VAC revealed PM ethanol production in only 4 victims (BAC: 25 mg/dL – 48 mg/dL). These false positive cases represented 0.4% of drownings with BAC > 0 mg/dL and 14.3% of drownings with BAC > 0 mg/dL and <50 mg/dL. Conclusions: The present study suggests that PM ethanol production has a limited impact on research addressing the prevalence rate for alcohol-related drowning and that the use of too rigorous exclusion criteria, such as those previously recommended, may led to a significant underestimation of actual alcohol-positive drowning cases. © 2018, The Author(s).
  • Pajunen, Tuulia; Vuori, Erkki; Lunetta, Philippe (Springer International Publishing, 2018)
    Abstract Background Post-mortem (PM) ethanol production may hamper the interpretation of blood alcohol concentration (BAC) in victims of drowning. Different exclusion criteria (e.g. cases with low BAC or with protracted interval between death and toxicological analysis) have been proposed with no factual figures to reduce the potential bias due to PM ethanol production when examining the prevalence rates for alcohol-related drowning. The aim of this study is to verify the extent to which PM alcohol production may affect the accuracy of studies on drowning and alcohol. Findings Unintentional fatal drowning cases (n = 967) for which a full medico-legal autopsy and toxicological analysis was performed, in Finland, from 2000 to 2013, and relevant variables (demographic data of the victims, month of incident, PM submersion time, blood alcohol concentration, urine alcohol concentration (UAC), vitreous humour alcohol concentration (VAC) were available. Overall, out of 967 unintentional drownings, 623 (64.4%) were positive for alcohol (BAC > 0 mg/dL), 595 (61.5%) had a BAC ≥ 50 mg/dL, and 567 (58.6%) a BAC ≥ 100 mg/dL. Simultaneous measurements, in each victim, of BAC, UAC, and VAC revealed PM ethanol production in only 4 victims (BAC: 25 mg/dL – 48 mg/dL). These false positive cases represented 0.4% of drownings with BAC > 0 mg/dL and 14.3% of drownings with BAC > 0 mg/dL and < 50 mg/dL. Conclusions The present study suggests that PM ethanol production has a limited impact on research addressing the prevalence rate for alcohol-related drowning and that the use of too rigorous exclusion criteria, such as those previously recommended, may led to a significant underestimation of actual alcohol-positive drowning cases.
  • Chd Exome Consortium; Consortium Genetics Smoking; EPIC-CVD Consortium; Understanding Soc Sci Grp; Brazel, David M.; Jiang, Yu; Hughey, Jordan M.; Loukola, Anu; Qaiser, Beenish; Kaprio, Jaakko; Kontto, Jukka; Perola, Markus; Dunning, Alison M. (2019)
    BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed similar to 250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
  • Sahlman, Perttu; Nissinen, Markku; Puukka, Pauli; Jula, Antti; Salomaa, Veikko; Männistö, Satu; Lundqvist, Annamari; Valsta, Liisa; Perola, Markus; Färkkilä, Martti; Åberg, Fredrik (2019)
    Background and Aim Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. Methods Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41 260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. Results A total of 355 liver events occurred during the mean 12.4-year follow-up (511 789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P = 0.0083 for men; HR 1.04, P = 0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P = 0.0006 for men; HR 1.58, P = 0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P = 0.024 for men; HR 2.7, P = 0.0109 for women), and weekly binge drinking (HR 2.4, P = 0.0024 for men; HR 7.4, P <0.0001 for women) predicted development of severe liver disease. Among men, diabetes (HR 2.7, P = 0.0002), average alcohol consumption (HR for 10 g/day 1.1, P = 0.0022), non-married status (HR 1.9, P = 0.0397 for single; HR 2.4, P = 0.0002 for widowed/separated), and serum high-density lipoprotein (HR 2.2, P = 0.0022) and non-high-density lipoprotein cholesterol (HR 1.2, P = 0.0237) were additional risk factors. Alcohol intake increased the risk especially among persons with high WHR (P for interaction 0.009). Conclusions Age, patatin-like phospholipase-containing domain 3 haplotype, and WHR increase the risk for development of severe liver disease. We found strong synergism between alcohol and central obesity. Binge drinking is an additional risk factor.
  • Sarmalinna, Oona (Helsingin yliopisto, 2018)
    Fetaalialkoholisyndrooma (FAS) on oireyhtymä, joka johtuu äidin raskaudenaikaisesta alkoholinkäytöstä. FAS-oireyhtymää esiintyy 1-2 lapsella jokaista tuhatta syntyvää lasta kohden. Diagnoosin muodostaa eri oireiden yhdistelmä: lapsen raskaudenaikainen ja syntymän jälkeinen kasvuhäiriö, keskushermoston toimintahäiriöt, kasvojen tyypilliset piirteet ja muut elimistön epämuodostumat. Edellä mainittujen oireiden lisäksi sikiöaikainen runsas alkoholialtistus on varmistettu. Huuli- ja suulakihalkiot ovat yksi yleisimmistä synnynnäisistä kasvojen epämuodostumista lapsilla. Niitä esiintyy jopa yhdellä lapsella jokaista viittäsataa syntyvää lasta kohden. Halkiot syntyvät sikiölle ensimmäisen raskauskolmanneksen aikana. Halkioiden syntymekanismi on monitekijäinen eli siihen vaikuttavat sekä perimä että ympäristötekijät. Tutkielman tavoitteena on kuvata FAS-lapsen, jolla on halkio, hampaiston ja kasvojen rakenteet, ja verrata niitä FAS-lapsen ja halkiolapsen vastaaviin rakenteisiin. Tutkimus sisältää kirjallisuuskatsauksen ja asiakirjatutkimuksen. Asiakirjatutkimus tehtiin neljän potilaan hampaiston ja leukojen hoitoon liittyvistä röntgenkuvista. Ptg-kuvista laskettiin lasten hampaistoikä ja arvioitiin sen korrelointia kronologiseen ikään. Kallolateraalikuvista arvioitin pehmytkudokset ja leukojen, hampaiston ja kallon väliset suhteet. Aineisto on peräisin Huuli- ja suulakihalkiokeskuksesta. Lapsilla, joilla on sekä FAS-oireyhtymä että halkio, esiintyi enemmän hampaistoiän jälkeenjääneisyyttä ja maksillan retrognatiaa, kuin lapsilla, joilla oli vain FAS-oireyhtymä tai halkio. Hampaistoiän jälkeenjääneisyyttä lisäsi halkion vakavuus. Nämä erityiset piirteet tulisi huomioida lapsen, jolla on sekä FAS-oireyhtymä että halkio, hoidossa ja diagnostiikassa. Potilasaineiston pienuuden ja hajanaisuuden vuoksi varmempien johtopäätösten tekeminen vaatii kuitenkin lisätutkimuksia laajemmalla potilasaineistolla.
  • Laukkanen, Virpi; Kärkkäinen, Olli; Kautiainen, Hannu; Tiihonen, Jari; Storvik, Markus (2019)
    The function of group I metabotropic glutamate receptors mGluR1 and mGluR5 is involved in the hyperglutamatergic state caused by chronic alcohol. Preclinical studies suggest that group I mGluR modulation could serve as a novel treatment of alcoholism. Considering the wide role of glutamatergic neurochemistry in addiction, group I mGluR binding was studied in brain areas involved in decision-making, learning and memory. Post-mortem whole hemisphere autoradiography was used to study the binding density of [H-3] quisqualic acid, a potent group I mGluR agonist, in 9 Cloninger type 1 alcoholics, 8 Cloninger type 2 alcoholics and 10 controls. Binding was studied in the dorsal striatum, hippocampus and cortex. Alcoholics displayed a trend towards increased [ H-3] quisqualic acid binding in all brain areas. The most robust findings were in the putamen (p = 0.006) and anterior insula (p = 0.005), where both alcoholic subtypes displayed increased binding compared to the controls. These findings suggest altered group I mGluR function in alcoholic subjects in the dorsal striatum, which is involved in habitual learning, and in the anterior insula, which has a pivotal role in the perception of bodily sensations. Increased [H-3] quisqualic acid binding might suggest a beneficial impact of mGluR1/5 modulators in the treatment of alcoholism.
  • Salaspuro, Mikko (2017)
    Ethanol is neither genotoxic nor mutagenic. Its first metabolite acetaldehyde, however, is a powerful local carcinogen. Point mutation in ALDH2 gene proves the causal relationship between acetaldehyde and upper digestive tract cancer in humans. Salivary acetaldehyde concentration and exposure time are the two major and quantifiable factors regulating the degree of local acetaldehyde exposure in the ideal target organ, oropharynx. Instant microbial acetaldehyde formation from alcohol represents >70% of total ethanol associated acetaldehyde exposure in the mouth. In the oropharynx and achlorhydric stomach acetaldehyde is not metabolized to safe products, instead in the presence of alcohol it accumulates in saliva and gastric juice in mutagenic concentrations. A common denominator in alcohol, tobacco and food associated upper digestive tract carcinogenesis is acetaldehyde. Epidemiological studies on upper GI tract cancer are biased, since they miss information on acetaldehyde exposure derived from alcohol and acetaldehyde present in 'non-alcoholic' beverages and food. (C) 2017 Published by Elsevier Ltd.
  • Lounassalo, Irinja; Hirvensalo, Mirja; Palomäki, Sanna; Salin, Kasper; Tolvanen, Asko; Pahkala, Katja; Rovio, Suvi; Fogelholm, Mikael; Yang, Xiaolin; Hutri-Kähönen, Nina; Raitakari, Olli T; Tammelin, Tuija H (BioMed Central, 2021)
    Abstract Background Evidence on whether leisure-time physical activity (LTPA) facilitates individuals’ adoption of multiple healthy behaviors remains scarce. This study investigated the associations of diverse longitudinal LTPA trajectories from childhood to adulthood with diet, screen time, smoking, binge drinking, sleep difficulties, and sleep duration in adulthood. Methods Data were drawn from the Cardiovascular Risk in Young Finns Study. Participants were aged 9–18 years (N = 3553; 51% females) in 1980 and 33–49 years at the latest follow-up in 2011. The LTPA trajectories were identified using a latent profile analysis. Differences in self-reported health-related behaviors across the LTPA trajectories were studied separately for women and men by using the Bolck-Croon-Hagenaars approach. Models were adjusted for age, body mass index, education level, marital status, total energy intake and previous corresponding behaviors. Results Persistently active, persistently low-active, decreasingly and increasingly active trajectories were identified in both genders and an additional inactive trajectory for women. After adjusting the models with the above-mentioned covariates, the inactive women had an unhealthier diet than the women in the other trajectories (p <  0.01; effect size (ES) > 0.50). The low-active men followed an unhealthier diet than the persistently and increasingly active men (p <  0.01; ES > 0.50). Compared to their inactive and low-active peers, smoking frequency was lower in the increasingly active women and men (p <  0.01; ES > 0.20) and persistently active men (p <  0.05; ES > 0.20). The increasingly active men reported lower screen time than the low-active (p <  0.001; ES > 0.50) and persistently active (p <  0.05; ES > 0.20) men. The increasingly and persistently active women reported fewer sleep difficulties than the inactive (p <  0.001; ES > 0.80) and low-active (p <  0.05; ES > 0.50 and > 0.80, respectively) women. Sleep duration and binge drinking were not associated with the LTPA trajectories in either gender, nor were sleep difficulties in men and screen time in women. Conclusions Not only persistently higher LTPA but also an increasing tendency to engage in LTPA after childhood/adolescence were associated with healthier diet and lower smoking frequency in both genders, having less sleep difficulties in women and lower screen time in increasingly active men. Inactivity and low activity were associated with the accumulation of several unhealthy behaviors in adulthood. Associations were stronger in women.
  • Salaspuro, Mikko (2020)
    Background:Alcohol consumption and ethanol in alcoholic beverages are group 1 carcinogens, that is, carcinogenic to humans. However, ethanol itself is neither genotoxic nor mutagenic. Based on unique gene-epidemiologic and gene-biochemical evidence, the first metabolite of ethanol oxidation - acetaldehyde (ACH) - acts as a local carcinogen in the oropharynx. This review is focused on those facts, which highlight the importance of the oropharynx and local ACH in the pathogenesis of alcohol-related oropharyngeal cancer.Summary:The strongest evidence for the local carcinogenicity of ACH in man provides a point mutation in the aldehyde dehydrogenase 2 (ALDH2) gene, which has randomized millions of alcohol consumers to markedly increased ACH exposure via saliva. This novel human cancer model is associated with manifold risk for oropharyngeal cancer and most importantly it is free from confounding factors markedly hampering epidemiological studies on alcohol-related cancer. The oropharynx is an ideal target organ for the cancer risk assessment of ACH. There is substantial epidemiological data on alcohol-related oropharyngeal cancer risk and also on salivary ACH concentrations among major risk groups for oropharyngeal cancer. Normal human saliva does not contain measurable levels of ACH. However, alcohol ingestion results within seconds in a concentration-dependent accumulation of ACH in saliva, which continues for up to 10-15 min after each sip of alcoholic beverage. This instant ACH exposure phase is followed by a long-term phase derived from ethanol diffused back to saliva from blood circulation. Microbes representing normal oral flora play a major role in local ACH formation from ethanol. In ALDH2-deficient subjects excess ACH during the long-term ACH exposure phase is most probably derived from salivary glands.Key Message:ALDH2gene mutation proves the causal relationship between local ACH exposure via saliva and oropharyngeal cancer and provides new means for the quantitative assessment of local ACH exposure in relation to oropharyngeal cancer risk. Instant ACH formation from ethanol represents approximately 70-100% of total local ACH exposure. Ethanol present in "non-alcoholic" beverages and food forms an epidemiological bias in studies on alcohol-related upper digestive tract cancer.Responses:One should quit smoking, adopt sensible drinking habits, and maintain good oral hygiene. Genetic risk groups could be screened and educated. Consumption of beverages and foodstuffs containing low ethanol levels as well as alcoholic beverages containing high ACH levels should be minimized. To that aim, labelling of alcohol and ACH concentrations of all beverages and foodstuffs should be mandatory.
  • Einiö, Elina; Hiltunen, Elina; Martikainen, Pekka; Korhonen, Kaarina (2020)
    Background: Men's age at first birth may negatively or positively affect alcohol-related morbidity and mortality, although little evidence is available. Methods: We used register data of over 22,000 brothers to analyze the associations between age at first birth and alcohol-related morbidity and mortality from the age of 35 until the age of 60 or 72. We employed conventional Cox models and inter-sibling models, which allowed adjustment for unobserved social and genetic characteristics shared by brothers. Results: The findings show that men's age at first birth was inversely associated with alcohol-related morbidity and mortality, independent of unobserved characteristics shared by brothers and of observed demographic confounders. Men who had their first child late at 35-45 years experienced lower alcohol-related morbidity and mortality (hazard ratio (HR) = 0.57, 95 % confidence interval (CI) = 0.43, 0.75) than men who had their first child at 25-29. Men who had their first child before age 20 had the highest morbidity and mortality among all fathers (HR = 1.36, 95 % CI = 1.09, 1.69), followed by men who had their child at 20-24 (HR = 1.12, 95 % CI = 1.00, 1.25). Conclusions: The results imply that the inverse association between men's age at first birth and alcohol-related morbidity and mortality is not driven by familial characteristics.