RESUMO
The nicotine acetylcholinergic receptor (nAchR) in the central nucleus of the amygdala (CeA) is known to modulate anxiety traits as well as ethanol-induced behavioral effects. Therefore, the present study investigated the role of CeA nAChR in the tolerance to ethanol anxiolysis and withdrawal-induced anxiety-related effects in rats on elevated plus maze (EPM). To develop ethanol dependence, rats were given free access to an ethanol-containing liquid diet for 10 days. To assess the development of tolerance, separate groups of rats were challenged with ethanol (2 g/kg, i.p.) on days 1, 3, 5, 7 and 10 during the period of ethanol exposure, followed by an EPM assessment. Moreover, expression of ethanol withdrawal was induced after switching ethanol-dependent rats to a liquid diet on day 11, and withdrawal-induced anxiety-like behavior was noted at different post-withdrawal time points using the EPM test. The ethanol-dependent rats were pretreated with intra-CeA (i.CeA) (bilateral) injections of nicotine (0.25â µg/rat) or mecamylamine (MEC) (5 ng/rat) before the challenge dose of ethanol on subthreshold tolerance on the 5th day or on peak tolerance day, that is, 7th or 10th, and before assessment of postwithdrawal anxiety on the 11th day on EPM. Bilateral i.CeA preadministration of nicotine before the challenge dose of ethanol on days 5, 7 and 10 exhibited enhanced tolerance, while injection of MEC, completely mitigated the tolerance to the ethanol-induced antianxiety effect. On the other hand, ethanol-withdrawn rats pretreated i.CeA with nicotine exacerbated while pretreatment with MEC, alleviated the ethanol withdrawal-induced anxiety on all time points. Thus, the present investigation indicates that stimulation of nAChR in CeA negatively modulates the ethanol-induced chronic behavioral effects on anxiety in rats. It is proposed that nAChR antagonists might be useful in the treatment of alcohol use disorder and ethanol withdrawal-related anxiety-like behavior.
Assuntos
Alcoolismo , Núcleo Central da Amígdala , Receptores Nicotínicos , Masculino , Animais , Ratos , Nicotina/farmacologia , Ansiedade/tratamento farmacológico , Etanol/farmacologiaRESUMO
Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a "neural addiction" property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3ß/ß-catenin signaling pathway partially through the influx of Ca2+-mediated activation of Ca/calmodulin-dependent protein kinases (CAMKII). In addition, acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor (BDNF), which formed a feedforward acetylcholine-BDNF axis to promote ICC progression. KN93, a small-molecule inhibitor of CAMKII, significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells. Above all, Acetylcholine/CHRNA5 axis increased the expression of ß-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKII/GSK3ß signaling, and the CAMKII inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.
Assuntos
Benzilaminas , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , beta Catenina/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Nicotina , Acetilcolina , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Gencitabina , Glicogênio Sintase Quinase 3 beta , Linhagem Celular Tumoral , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Neurotransmissores , Receptores Colinérgicos , Microambiente TumoralRESUMO
Currently, in the ongoing development of the tobacco industry, a large amount of tobacco rhizomes is discarded as waste. These wastes are usually disposed of through incineration or burial. However, these tobacco wastes still have some economic value. High-purity nicotine has a promising market outlook as the primary raw material for electronic cigarette liquid. Nicotine is not only found in tobacco leaves but also in the rhizomes of tobacco plants. This study presents a method for treating tobacco waste and extracting high-purity nicotine from it. After mixing the raw material powder and entrainer in specific ratios, as much of the nicotine in tobacco roots can be extracted as possible using supercritical carbon dioxide extraction. The effects of temperature, the ratio of the entrainer, and the volume fraction of ethanol in the entrainer on the nicotine yield in supercritical fluid extraction (SFE) at 25 MPa for 120 min were discussed. By using 90% ethanol (a raw material mass-to-volume ratio of 1:5) as the entrainer, we obtained the highest nicotine yield of 0.49% at 65 °C. Meanwhile, the purity of the crude extract was 61.71%, and after purification, it increased to 97.57%. In this way, we can not only obtain nicotine with market value but also further reduce the harm to the environment caused by tobacco waste disposal.
Assuntos
Cromatografia com Fluido Supercrítico , Sistemas Eletrônicos de Liberação de Nicotina , Rizoma , Nicotina , Dióxido de Carbono , Etanol , Cromatografia com Fluido Supercrítico/métodosRESUMO
One of the members of CYP, a monooxygenase, CYP2A13 is involved in the metabolism of nicotine, coumarin, and tobacco-specific nitrosamine. Genetic polymorphisms have been identified in CYP2A13, with reported loss or reduction in enzymatic activity in CYP2A13 allelic variants. This study aimed to unravel the mechanism underlying the diminished enzymatic activity of CYP2A13 variants by investigating their three-dimensional structures through molecular dynamics (MD) simulations. For each variant, MD simulations of 1000 ns were performed, and the obtained results were compared with those of the wild type. The findings indicated alterations in the interaction with heme in CYP2A13.4, .6, .8, and .9. In the case of CYP2A13.5, observable effects on the helix structure related to the interaction with the redox partner were identified. These conformational changes were sufficient to cause a decrease in enzyme activity in the variants. Our findings provide valuable insights into the molecular mechanisms associated with the diminished activity in the CYP2A13 polymorphisms.
Assuntos
Simulação de Dinâmica Molecular , Nitrosaminas , Polimorfismo Genético , Nicotina , Oxirredução , Citocromo P-450 CYP2A6/genéticaRESUMO
BACKGROUND: Varenicline is considered one of the most effective treatment options for smoking cessation. Nonetheless, it is only modestly effective. A deeper comprehension of the effects of varenicline by means of the in-depth review of relevant fMRI studies may assist in paving the development of more targeted and effective treatments. METHODOLOGY: A search of PubMed and Google Scholar databases was conducted with the keywords "functional magnetic resonance imaging" or "fMRI", and "varenicline". All peer-reviewed articles regarding the assessment of smokers with fMRI while undergoing treatment with varenicline and meeting the predefined criteria were included. RESULTS: Several studies utilizing different methodologies and targeting different aspects of brain function were identified. During nicotine withdrawal, decreased mesocorticolimbic activity and increased amygdala activity, as well as elevated amygdala-insula and insula-default-mode-network functional connectivity are alleviated by varenicline under specific testing conditions. However, other nicotine withdrawal-induced changes, including the decreased reward responsivity of the ventral striatum, the bilateral dorsal striatum and the anterior cingulate cortex are not influenced by varenicline suggesting a task-dependent divergence in neurocircuitry activation. Under satiety, varenicline treatment is associated with diminished cue-induced activation of the ventral striatum and medial orbitofrontal cortex concomitant with reduced cravings; during the resting state, varenicline induces activation of the lateral orbitofrontal cortex and suppression of the right amygdala. CONCLUSIONS: The current review provides important clues with regard to the neurobiological mechanism of action of varenicline and highlights promising research opportunities regarding the development of more selective and effective treatments and predictive biomarkers for treatment efficacy.
Assuntos
Abandono do Hábito de Fumar , Síndrome de Abstinência a Substâncias , Humanos , Vareniclina/farmacologia , Vareniclina/uso terapêutico , Abandono do Hábito de Fumar/métodos , Nicotina , Imageamento por Ressonância Magnética , Agonistas Nicotínicos/uso terapêutico , Encéfalo/diagnóstico por imagemRESUMO
This review discusses the diverse effects of nicotine on the various nicotinic acetylcholine receptors of the central and peripheral nervous system and how those effects may promote the usage and addiction to tobacco products.
Assuntos
Receptores Nicotínicos , Tabagismo , Humanos , Nicotina/farmacologiaRESUMO
Nicotine has been well-characterized for its ability to alter neurophysiology to promote rewarding and reinforcing properties. However, several exogenous chemicals possess properties that modulate or enhance nicotine's ability to alter neurophysiology. This chapter focuses on nicotine's impact on behavior through changes in neurophysiology and several chemical entities that in-turn modulate nicotine's ability to act as a neuromodulator.
Assuntos
Nicotina , Reforço Psicológico , Humanos , Nicotina/farmacologia , RecompensaAssuntos
Humanos , Feminino , Gravidez , Poluição por Fumaça de Tabaco , Cannabis , Drogas Ilícitas/efeitos adversos , Fumaça , Etanol , Analgésicos Opioides , NicotinaRESUMO
The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies. In the Multiethnic Cohort Study (discovery, n = 1994), TNEs were associated with differential methylation at 408 CpG sites across >250 genomic regions (p < 9 × 10-8). The top significant sites were annotated to AHRR, F2RL3, RARA, GPR15, PRSS23, and 2q37.1, all of which had decreasing methylation with increasing TNEs. We identified 45 novel CpG sites, of which 42 were unique to the EPIC array and eight annotated to genes not previously linked with smoking-related DNA methylation. The most significant signal in a novel gene was cg03748458 in MIR383;SGCZ. Fifty-one of the 408 discovery sites were validated in the Singapore Chinese Health Study (n = 340) and the Southern Community Cohort Study (n = 394) (Bonferroni corrected p < 1.23 × 10-4). Significant heterogeneity by race and ethnicity was detected for CpG sites in MYO1G and CYTH1. Furthermore, TNEs significantly mediated the association between cigarettes per day and DNA methylation at 15 sites (average 22.5%-44.3% proportion mediated). Our multiethnic study highlights the transethnic and ethnic-specific methylation associations with internal nicotine dose, a strong predictor of smoking-related morbidities.
Assuntos
MicroRNAs , Fumantes , Humanos , Nicotina , Epigênese Genética/genética , Epigenoma , Estudos de Coortes , Estudos Prospectivos , Estudo de Associação Genômica Ampla , Metilação de DNA/genética , Ilhas de CpG/genética , Receptores de Peptídeos/genética , Receptores Acoplados a Proteínas G/genéticaRESUMO
Consumption of e-cigarettes (particularly the famous "puffs") and other nicotine products has risen sharply among Swiss teenagers, and now exceeds consumption of traditional cigarettes. Yet these products are harmful to health. Nicotine is highly addictive for young people, and e-cigarette use causes significant respiratory morbidity for both active and passive users. We are just measuring the extent of the toxic effects of these products, given their recent appearance on the market, but the initial scientific evidence is extremely worrisome and calls for a rapid response. Prevention among young people is crucial, and better legislation is urgently needed.
La consommation d'e-cigarettes (notamment des fameuses « puffs ¼) et d'autres produits nicotiniques a fortement augmenté chez les adolescents suisses, dépassant désormais la consommation de cigarettes traditionnelles. Ces produits sont pourtant nocifs pour la santé. La nicotine a un très fort pouvoir addictif chez les jeunes et la consommation d'e-cigarette induit une importante morbidité respiratoire pour les consommateurs actifs mais aussi passifs. Nous mesurons à peine l'étendue des effets toxiques de ces produits vue leur apparition récente sur le marché, mais les premiers éléments scientifiques sont extrêmement préoccupants et appellent à une réaction rapide. La prévention auprès des jeunes est capitale et un meilleur encadrement législatif nécessaire.
Assuntos
Comportamento Aditivo , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adolescente , Humanos , Nicotina/efeitos adversos , Comportamento Aditivo/epidemiologiaRESUMO
Tobacco smoking is a serious health problem in society. While smoking rates are declining, smoking remains a serious risk to national health. Currently, there are several medications available to aid in smoking cessation. However, these medications have the disadvantages of low success rates in smoking cessation and various side effects. Therefore, natural-based smoking cessation aids are being suggested as a good alternative due to their accessibility and minimal side effects. The roots and stems of Acanthopanax koreanum (AK) Nakai, a plant that is native to Jeju Island, South Korea, have traditionally been used as tonic and sedatives. Moreover, eleutheroside B and chlorogenic acid are the main components of AK stem extract. In the present study, we investigated the effect of 70% ethanol AK extract and its components on ameliorating nicotine dependence and withdrawal symptoms by using behavioural tests in mice. In addition, alterations in the dopaminergic and DRD1-EPAC-ERK-CREB pathways were observed using dopamine ELISA and western blotting using mouse brains. Our findings demonstrate that the AK extract and its components effectively mitigated the effects of nicotine treatment in behavioural tests. Furthermore, it normalized the dopamine concentration and the expression level of nicotine acetylcholine receptor α7. Additionally, it was observed that AK extract and its components led to the normalization of DRD1, ERK and CREB expression levels. These results indicate that AK extract exhibits effects in ameliorating nicotine dependence behaviour and alleviating withdrawal symptoms. Moreover, EB and CGA are considered potential marker components of AK extract.
Assuntos
Eleutherococcus , Síndrome de Abstinência a Substâncias , Tabagismo , Animais , Camundongos , Tabagismo/tratamento farmacológico , Nicotina/efeitos adversos , Dopamina , Síndrome de Abstinência a Substâncias/tratamento farmacológico , EtanolRESUMO
BACKGROUND: Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface. METHODS: Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure. RESULTS: PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm². CONCLUSION: Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , Adolescente , Nicotina/toxicidade , Vaping/efeitos adversos , Sais , Solventes , Propilenoglicol/toxicidade , Propilenoglicol/química , Glicerol/química , Glicerol/farmacologia , Aerossóis , Aromatizantes , InflamaçãoRESUMO
Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Aprendizado Profundo , Gravidez , Feminino , Animais , Camundongos , Nicotina/efeitos adversos , Comportamento SocialRESUMO
BACKGROUND: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes. METHODS: Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts. The first cohort underwent exposure to air/EC preceding randomization to transient middle cerebral artery occlusion (90 minutes) or sham surgery, followed by survival for 21 days. During the survival period, rats underwent sensorimotor and Morris water maze testing. Subsequently, brains were collected for histopathology. A second cohort was exposed to air/EC after which brains were collected for unbiased metabolomics analysis. The third cohort of animals was exposed to air/EC and received transient middle cerebral artery occlusion/sham surgery, and brain tissue was collected 24 hours later for biochemical analysis. RESULTS: In females, EC significantly increased (P<0.05) infarct volumes by 94% as compared with air-exposed rats, 165±50 mm3 in EC-exposed rats, and 85±29 mm3 in air-exposed rats, respectively, while in males such a difference was not apparent. Morris water maze data showed significant deficits in spatial learning and working memory in the EC sham or transient middle cerebral artery occlusion groups compared with the respective air groups in rats of both sexes (P<0.05). Thirty-two metabolites of carbohydrate, glycolysis, tricarboxylic acid cycle, and lipid metabolism were significantly altered (P≤0.05) due to EC, 23 of which were specific for females. Steady-state protein levels of hexokinase significantly decreased (P<0.05) in EC-exposed females; however, these changes were not seen in males. CONCLUSIONS: Even brief EC exposure over 2 weeks impacts brain energy metabolism, exacerbates infarction, and worsens poststroke cognitive deficits in working memory more in female than male rats.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , Adulto , Ratos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Nicotina/efeitos adversos , Infarto da Artéria Cerebral Média/metabolismoRESUMO
BACKGROUND: Flavored novel oral nicotine products (ONP), such as pouches, gum, lozenges, tablets, and gummies, have recently entered the US market but have not been authorized for smoking cessation. This study assessed the prevalence and correlates of ONPs in a national sample of youth who smoked little filtered cigars or cigarillos (LCCs) or were susceptible to LCCs. METHODS: We conducted a national online survey from September-October 2022, as part of a study to develop cigar warnings among youth. Those aged 15-20 years old who reported using (ever or current) or susceptibility to little filtered cigars or cigarillos (LCCs) were eligible. Descriptive statistics and chi-square analyses assessed the prevalence of flavored ONP use and associations with other past 30-day tobacco product use and participant characteristics. RESULTS: Approximately one-fifth (17.1 %) of the sample (n = 680) reported past month flavored ONP use. Any past month tobacco use was correlated with past month flavored ONP use (ps < 0.001), increasing from 17.1 % in the overall sample to 26.8 % among those reporting e-cigarette use, 41.4 % (LCCs), 47.8 % (waterpipe tobacco), 61.8 % (large cigars), and 69.1 % (smokeless tobacco). The number of products used in the past month was significantly associated with higher odds of ONPs in the past month in a multivariable logistic regression model (aOR2.26; 95 % CI: 1.92, 2.65). DISCUSSION: Almost one-fifth of participants who use or are susceptible to cigar use in our national sample of youth use ONPs. Dual/poly use of other tobacco products and ONPs among youth suggests that many of these youth may be addicted to nicotine. Additional surveillance and regulation of ONPs that exhibit enticing characteristics, such as flavors, kid-friendly formulations, and targeted marketing/branding may be needed.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Adolescente , Adulto Jovem , Adulto , Nicotina , Prevalência , Fumar/epidemiologiaRESUMO
CONTEXT: Current use and potential future uptake of e-cigarettes among youth remain public health concerns in the U.S., even as people who smoke combustible cigarettes could benefit from switching completely to e-cigarettes. The U.S. Food and Drug Administration (FDA) is considering alternative warning messages, but warnings that discourage youth from use may also deter people who smoke from switching. This study tests ten pre-registered hypotheses on effects of warning messages with national samples of youth overall and adults who smoke and/or vape. METHODS: NORC recruited 1639 adults (ages 18+) who smoke, vape, or use both products, from their probability-sampled AmeriSpeak Panel and augmented their AmeriSpeak Teen Panel with Lucid's nonprobability opt-in panel to recruit 1217 youth (ages 14-17) to participate in a web-based survey experiment. We randomly assigned respondents to view one of five warning label conditions and respond to measures of their e-cigarette risk beliefs, willingness to use e-cigarettes, and (among people who smoke or vape) considerations to quit these products. FINDINGS: Relative to the current FDA warning about nicotine, warning messages about the harms of e-cigarette use for youth brain development did not influence risk beliefs or reduce willingness to use these products among youth. Brain development warning messages did increase beliefs about these harms among adults but did not increase quit considerations among people who vape, relative to the FDA warning. Warning messages with information about chemical constituents of vaping products and the harm of these chemicals produced higher e-cigarette quit considerations than did the FDA warning among adults who vape. CONCLUSION: Potential alternative warning label messages were largely ineffective relative to the current FDA warning about nicotine, though limited evidence suggests some potential for chemical + harm messaging to encourage people who use both e-cigarettes and cigarettes to consider quitting both.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Estados Unidos , Adulto , Humanos , Adolescente , Nicotina , Publicidade , Vaping/efeitos adversos , PolíticasRESUMO
INTRODUCTION: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. METHODS: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. RESULTS: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. CONCLUSION: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.
Assuntos
Ácido Glutâmico , Nicotina , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem , BiomarcadoresRESUMO
Wastewater-based epidemiology (WBE) was applied to evaluate the consumption trends of pharmaceuticals (i.e., antibiotics, non-steroidal anti-inflammatory drugs, antiepileptics, antihypertensives, and others), as well as recreational drugs (caffeine, alcohol, and nicotine), in Latvia from December 2020 to July 2023. The time period covers both the COVID-19 pandemic and the post-pandemic periods; therefore, the impact of the implemented restrictions and the consequences of the illness in terms of the usage of pharmaceuticals thereon were investigated. Additionally, the seasonality and impact of the seasonal flu and other acute upper respiratory infections were studied. The results revealed that the pandemic impacted the consumption of alcohol, nicotine, and caffeine, as well as several pharmaceuticals, such as antihypertensives, antidepressants, psychiatric drugs, and the painkiller ibuprofen. The findings suggest that the imposed restrictions during the pandemic may have had a negative effect on the population's health and mental well-being. Distinct seasonal trends were discovered in the consumption patterns of caffeine and alcohol, where lower use was observed during the summer. The seasonal consumption trends of pharmaceuticals were discovered in the case of antibiotics, the antiasthmatic drug salbutamol, and the decongestant xylometazoline, where higher consumption occurred during colder seasons.