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Shin JM, Jeong Y, Kim J, Lee J, Kim TH. Assessing the Complex Impact of Smoking Habits on Allergic Rhinitis: A National Cross-Sectional Study. Clin Exp Otorhinolaryngol 2025; 18:30-39. [PMID: 39581678 PMCID: PMC11917198 DOI: 10.21053/ceo.2024.00202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 11/24/2024] [Indexed: 11/26/2024] Open
Abstract
OBJECTIVES Allergic rhinitis (AR) significantly impacts quality of life and incurs socioeconomic costs. The influence of smoking habits, including the use of conventional cigarettes (CCs) and electronic cigarettes (ECs), on the prevalence and management of AR remains a subject of debate. This study aims to explore the association between smoking status (CC and EC use) and the prevalence and management of AR among Koreans by analyzing data from the Korea National Health and Nutrition Examination Survey (KNHANES) VII (2018) and VIII (2019-2021). METHODS This cross-sectional study involved 22,290 participants aged 19 years and older from the KNHANES. Participants self-reported their smoking status, and urinary cotinine levels were measured to assess nicotine exposure. We employed statistical analyses, including logistic regression, to examine the relationships between smoking status, cotinine levels, and the prevalence and management of AR. RESULTS In univariable logistic regression analysis, EC users exhibited a 35.8% increased risk of AR compared to non-smokers, whereas CC users experienced a 27.7% reduced risk. Multivariable logistic regression analysis showed a 20.3% lower risk of AR among CC users; however, no significant association was observed for EC users. Higher cotinine levels (>500 ng/mL) were associated with a lower prevalence of AR. Specifically, heavy CC users with high cotinine levels demonstrated a 35% reduced risk of AR. Nonetheless, after adjusting for confounders, this association was no longer significant, indicating that other variables might influence this relationship. CONCLUSION Smoking status is associated with the prevalence of AR in Koreans. Notably, heavy use of CCs is negatively correlated with the prevalence of AR.
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Affiliation(s)
- Jae-Min Shin
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul, Korea
| | - Yujin Jeong
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Jaehyeong Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul, Korea
| | - Juhyun Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
| | - Tae Hoon Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
- Mucosal Immunology Institute, Korea University College of Medicine, Seoul, Korea
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Idrees SM, Waite SL, Granados Aparici S, Fenwick MA. Nicotine exposure is associated with targeted impairments in primordial follicle phenotype in cultured neonatal mouse ovaries. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 288:117302. [PMID: 39546863 DOI: 10.1016/j.ecoenv.2024.117302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/29/2024] [Accepted: 11/05/2024] [Indexed: 11/17/2024]
Abstract
The ovarian reserve consists of a limited supply of primordial follicles (PFs), each containing an oocyte surrounded by a layer of granulosa cells (GCs). PFs are relatively quiescent and must remain viable for a long period, thereby making them susceptible to environmental and lifestyle influences. Given the widespread prevalence of e-cigarette use, this study aimed to investigate the effects of nicotine and its metabolite cotinine in a mouse model and to elucidate the mechanisms by which nicotine influences the ovarian reserve. Neonatal ovaries were cultured for 7-days in nicotine or cotinine reflective of concentrations in plasma of e-cigarette users. From histological evaluation, nicotine or cotinine had no impact on the number of PFs or early growing follicles; however, the medium (15 ng/ml) and high (45 ng/ml) concentrations of nicotine (but not cotinine) caused a small reduction in oocyte and GC size within PFs relative to controls (0 ng/ml; both P<0.01). These morphological effects were not associated with changes in immunofluorescent markers of apoptosis (active caspase-3) or proliferation (Pcna), but were associated with increased gH2AX in PF oocytes, indicative of DNA damage and repair. RNA-sequencing of cultured ovaries exposed to nicotine (45 ng/ml) relative to control (0 ng/ml), revealed a suite of differentially expressed candidates, as well as numerous gene ontology biological processes associated with increased DNA damage, metabolism, respiration and immune function, alongside suppression of meiosis, cell adhesion, differentiation and morphogenesis. Findings from this study indicate that direct nicotine exposure has a limited effect on the quantity of PFs, but importantly highlights a range of processes that could impinge on the quality of the ovarian reserve.
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Affiliation(s)
- Sara M Idrees
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2SF, UK
| | - Sarah L Waite
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2SF, UK
| | - Sofia Granados Aparici
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2SF, UK
| | - Mark A Fenwick
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2SF, UK.
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Kijpaisalratana N, Ament Z, Patki A, Bhave VM, Jones AC, Couch CA, Guarniz ALG, Cushman M, Long DL, Judd SE, Irvin MR, Kimberly WT. Plasma Metabolites and Life's Simple 7 in REGARDS. Stroke 2024; 55:1191-1199. [PMID: 38482689 PMCID: PMC11039367 DOI: 10.1161/strokeaha.123.044714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 01/31/2024] [Indexed: 04/24/2024]
Abstract
BACKGROUND The American Heart Association's Life's Simple 7 (LS7) is a health metric that captures important factors associated with cardiovascular and cerebrovascular health. Previous studies highlight the potential of plasma metabolites to serve as a marker for lifestyle and health behavior that could be a target for stroke prevention. The objectives of this study were to identify metabolites that were associated with LS7 and incident ischemic stroke and mediate the relationship between the two. METHODS Targeted metabolomic profiling of 162 metabolites by liquid chromatography-tandem mass spectrometry was used to identify candidate metabolites in a stroke case-cohort nested within the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Weighted linear regression and weighted Cox proportional hazard models were used to identify metabolites that were associated with LS7 and incident ischemic stroke, respectively. Effect measures were based on a 1-SD change in metabolite level. Metabolite mediators were examined using inverse odds ratio weighting mediation analysis. RESULTS The study comprised 1075 ischemic stroke cases and 968 participants in the random cohort sample. Three out of 162 metabolites were associated with the overall LS7 score including guanosine (β, -0.46 [95% CI, -0.65 to -0.27]; P=2.87×10-6), cotinine (β, -0.49 [95% CI, -0.70 to -0.28]; P=7.74×10-6), and acetylneuraminic acid (β, -0.59 [95% CI, -0.77 to -0.42]; P=4.29×10-11). Guanosine (hazard ratio, 1.47 [95% CI, 1.31-1.65]; P=6.97×10-11), cotinine (hazard ratio, 1.30 [95% CI, 1.16-1.44]; P=2.09×10-6), and acetylneuraminic acid (hazard ratio, 1.29 [95% CI, 1.15-1.45]; P=9.24×10-6) were associated with incident ischemic stroke. The mediation analysis identified guanosine (27% mediation, indirect effect; P=0.002), cotinine (30% mediation, indirect effect; P=0.004), and acetylneurminic acid (22% mediation, indirect effect; P=0.041) partially mediated the relationship between LS7 and ischemic stroke. CONCLUSIONS We identified guanosine, cotinine, and acetylneuraminic acid that were associated with LS7, incident ischemic stroke, and mediated the relationship between LS7 and ischemic stroke.
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Affiliation(s)
- Naruchorn Kijpaisalratana
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Zsuzsanna Ament
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
| | - Amit Patki
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | | | - Alana C Jones
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - Catharine A. Couch
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | | | - Mary Cushman
- Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT
| | - D. Leann Long
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - Suzanne E. Judd
- Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - M. Ryan Irvin
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - W. Taylor Kimberly
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA
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Palmisano AN, Schwartz EKC, Gueorguieva R, Sofuoglu M. Associations Between Childhood Trauma and Tobacco Use Outcomes in Adults after Overnight Abstinence. Nicotine Tob Res 2024; 26:324-332. [PMID: 37565294 PMCID: PMC10882440 DOI: 10.1093/ntr/ntad135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 06/16/2023] [Accepted: 07/27/2023] [Indexed: 08/12/2023]
Abstract
INTRODUCTION Childhood trauma is known to be associated with nicotine dependence, yet limited smoking outcomes have been examined and few studies have assessed associations between specific trauma subscales and smoking. Additionally, sex differences in trauma-smoking relations are understudied. This study examined associations between childhood trauma and several smoking-related outcomes in adults who smoke after overnight abstinence. AIMS AND METHODS People who smoke (N = 205) completed self-report and biochemical assessments evaluating childhood trauma, affect, nicotine dependence, smoking urges, withdrawal, and plasma cortisol and cotinine levels. Smoking outcomes were compared between those with and without a history of moderate to severe childhood trauma among the total sample and by sex. RESULTS Relative to those with no to minimal abuse, those with moderate to severe abuse had higher negative affect, withdrawal severity, and plasma cotinine levels. Exploratory analyses revealed that women were more likely than men to have urges to smoke for negative reinforcement and have higher withdrawal severity, but no interactions between abuse group and sex were observed. Examining specific trauma subscales, the moderate to severe emotional abuse group had more severe nicotine dependence, negative affect, and withdrawal compared to the no to minimal group. The moderate to severe sexual abuse group had more severe nicotine dependence and withdrawal compared to the no to minimal group. CONCLUSIONS Exposure to childhood trauma is associated with more severe nicotine dependence, negative affect, withdrawal, and higher plasma cotinine levels. Findings also indicate that different types of trauma may differentially affect smoking behaviors. IMPLICATIONS This study of adults who smoke finds that childhood trauma history may be a marker for smoking susceptibility and suggests that individuals with experiences of emotional and sexual abuse may require targeted forms of smoking cessation interventions. Moreover, findings suggest that smoking risks may differ for men and women. Findings inform public health interventions intended to reduce cigarette use in individuals with exposure to childhood trauma.
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Affiliation(s)
- Alexandra N Palmisano
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA
| | - Elizabeth K C Schwartz
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA
| | - Ralitza Gueorguieva
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA
| | - Mehmet Sofuoglu
- Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA
- U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA
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Kumboyono K, Chomsy IN, Shalshabilla NN, Sujuti H, Srihardyastutie A, Tjahjono CT, Heriansyah T, Wihastuti TA. Nicotine is associated with smoking dependence and vascular inflammation through cotinine: A mediation analysis. Tob Induc Dis 2024; 22:TID-22-16. [PMID: 38250634 PMCID: PMC10798223 DOI: 10.18332/tid/171356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 08/04/2023] [Accepted: 08/17/2023] [Indexed: 01/23/2024] Open
Abstract
INTRODUCTION The main alkaloid component in cigarettes is nicotine. Cotinine, a metabolite of nicotine, is capable of causing dependence effects through endless mechanisms modulated by the ion channel nicotinic acetylcholine receptors nAChRs. Nicotine and cotinine can also cause damage to blood vessels through a chronic inflammatory process mediated by the Ligand-Tie2 Angiopoietin Receptor system. Hypoxic conditions that occur due to vascular inflammation cause a decrease in the concentration of nitric oxide (NO). This study aimed to evaluate the relationship between NO levels and cotinine through the expression of nAChRs that mediate the nicotine dependence mechanism and Tie2 (Tyrosine Kinase 2) expression. METHODS A cross-sectional study was conducted with 200 participants grouped into two groups based on their smoking status: 100 smokers and 100 non-smokers. All participants were men aged 20-40 years with no history of cardiovascular disease, diabetes mellitus, or dyslipidemia, and were not currently on medication. According to the parameters used, all blood samples were taken from peripheral blood for analysis using the ELISA kit or Colorimetric Assay Kit. RESULTS Cigarette consumption increases blood cotinine concentrations in smokers and causes dependence by modulating nAChRs. The study indicates an emerging cycle regarding nicotine-cotinine consumption and nAChRs expression. In addition, the data in this study showed a significant relationship (p<0.001) regarding the cycle formed with decreased NO levels as a result of damage caused by Tie2-mediated inflammation. CONCLUSIONS There is a relationship between NO levels and cotinine through nAChRs, which mediate the nicotine dependence mechanism and Tie2 expression.
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Affiliation(s)
- Kumboyono Kumboyono
- Department of Nursing, Faculty of Health Sciences, University of Brawijaya, Malang, Indonesia
| | - Indah N. Chomsy
- Doctoral Program of Medical Science, Faculty of Medicine, University of Brawijaya, Malang, Indonesia
| | - Nadya N. Shalshabilla
- Master Program of Biomedical Science, Faculty of Medicine, University of Brawijaya, Malang, Indonesia
| | - Hidayat Sujuti
- Department of Biomolecular-Ophtalmology, Faculty of Medicine, University of Brawijaya-Saiful Anwar General Hospital, Malang, Indonesia
| | - Arie Srihardyastutie
- Department of Chemistry, Faculty of Mathematics and Natural Science, University of Brawijaya, Malang, Indonesia
| | - Cholid T. Tjahjono
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Brawijaya-Saiful Anwar General Hospital, Malang, Indonesia
| | - Teuku Heriansyah
- Department of Cardiology and Vascular Medicine, Syiah Kuala University, Banda Aceh, Indonesia
| | - Titin A. Wihastuti
- Department of Nursing, Faculty of Health Sciences, University of Brawijaya, Malang, Indonesia
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Lakes JE, Fu X, Harvey BT, Neupane KR, Aryal SP, Ferrell JL, Flythe MD, Richards CI. Impact of nicotine and cotinine on macrophage inflammatory plasticity via vesicular modifications in gastrointestinal bacteria. Anaerobe 2023; 83:102787. [PMID: 37827238 PMCID: PMC10841519 DOI: 10.1016/j.anaerobe.2023.102787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 09/26/2023] [Accepted: 10/03/2023] [Indexed: 10/14/2023]
Abstract
OBJECTIVES This study aimed to elucidate mechanistic explanation(s) for compositional changes to enteric microbiota by determining the impacts of continuous nicotine/cotinine exposure on representative gastrointestinal bacteria and how these alterations impact innate immune cell plasticity. METHODS In vitro cultures of the gastrointestinal bacteria (Bacteroides fragilis 25285, Prevotella bryantii B14, and Acetoanaerobium sticklandii SR) were continuously exposed to nicotine or cotinine. Supernatant samples were collected for fermentation acid analysis. Vesicles were collected and analyzed for physiological changes in number, size, and total protein cargo. Cultured macrophages were stimulated to a tolerogenic phenotype, exposed to control or altered (nicotine or cotinine - exposed) vesicles, and inflammatory plasticity assessed via inflammatory cytokine production. RESULTS Nicotine/cotinine exposure differentially affected metabolism of all bacteria tested in a Gram (nicotine) and concentration-dependent (cotinine) manner. Physiological studies demonstrated changes in vesiculation number and protein cargo following nicotine/cotinine exposures. Continuous exposure to 1 μM nicotine and 10 μM cotinine concentrations reduced total protein cargo of Gram (-) - 25285 and B14 vesicles, while cotinine generally increased total protein in Gram (+) - SR vesicles. We found that theses physiological changes to the vesicles of 25285 and SR formed under nicotine and cotinine, respectively, challenged the plasticity of tolerogenic macrophages. Tolerogenic macrophages exposed to vesicles from 1 μM nicotine, and 5 or 10 μΜ cotinine cultures produced significantly less IL-12p70, TNFα, or KC/GRO, regardless of macrophage exposure to nicotine/cotinine. CONCLUSIONS Nicotine/cotinine exposure differentially alters bacterial metabolism and vesicle physiology, ultimately impacting the inflammatory response of tolerogenic macrophages.
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Affiliation(s)
- Jourdan E Lakes
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA.
| | - Xu Fu
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA.
| | - Brock T Harvey
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA.
| | - Khaga R Neupane
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA.
| | - Surya P Aryal
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA.
| | - Jessica L Ferrell
- USDA Agricultural Research Service Forage-Animal Production Research Unit, Lexington, KY, USA.
| | - Michael D Flythe
- USDA Agricultural Research Service Forage-Animal Production Research Unit, Lexington, KY, USA; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, USA.
| | - Christopher I Richards
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA.
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Echeverria V, Mendoza C, Iarkov A. Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases. Front Neurosci 2023; 17:1179611. [PMID: 37255751 PMCID: PMC10225599 DOI: 10.3389/fnins.2023.1179611] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 04/07/2023] [Indexed: 06/01/2023] Open
Abstract
Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and connectivity of a particular arrangement of engram neurons, supported by the concerted action of neurons, glia, and vascular cells. The deterioration of the cholinergic system is a common occurrence in neurological conditions exacerbated by aging such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), Alzheimer's disease (AD), and Parkinson's disease (PD). Cotinine is a cholinergic modulator with neuroprotective, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. Current evidence suggests Cotinine's beneficial effects on cognition results from the positive modulation of the α7-nicotinic acetylcholine receptors (nAChRs) and the inhibition of the toll-like receptors (TLRs). The α7nAChR affects brain functions by modulating the function of neurons, glia, endothelial, immune, and dendritic cells and regulates inhibitory and excitatory neurotransmission throughout the GABA interneurons. In addition, Cotinine acting on the α7 nAChRs and TLR reduces neuroinflammation by inhibiting the release of pro-inflammatory cytokines by the immune cells. Also, α7nAChRs stimulate signaling pathways supporting structural, biochemical, electrochemical, and cellular changes in the Central nervous system during the cognitive processes, including Neurogenesis. Here, the mechanisms of memory formation as well as potential mechanisms of action of Cotinine on memory preservation in aging and neurological diseases are discussed.
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Affiliation(s)
- Valentina Echeverria
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Concepción, Chile
- Research and Development Department, Bay Pines VAHCS, Bay Pines, FL, United States
| | - Cristhian Mendoza
- Facultad de Odontologia y Ciencias de la Rehabilitacion, Universidad San Sebastián, Concepción, Chile
| | - Alex Iarkov
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Concepción, Chile
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Ahmad F. Medicinal nicotine in COVID-19 acute respiratory distress syndrome, the new corticosteroid. World J Crit Care Med 2022; 11:228-235. [PMID: 36051943 PMCID: PMC9305679 DOI: 10.5492/wjccm.v11.i4.228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 04/23/2022] [Accepted: 06/18/2022] [Indexed: 02/06/2023] Open
Abstract
The cholinergic anti-inflammatory pathway (CAP) refers to the anti-inflammatory effects mediated by the parasympathetic nervous system. Existence of this pathway was first demonstrated when acetylcholinesterase inhibitors showed benefits in animal models of sepsis. CAP functions via the vagus nerve. The systemic anti-inflammatory effects of CAP converges on the α7 nicotinic acetylcholine receptor on splenic macrophages, leading to suppression of pro-inflammatory cytokines and simultaneous stimulation of anti-inflammatory cytokines, including interleukin 10. CAP offers a novel mechanism to mitigate inflammation. Electrical vagal nerve stimulation has shown benefits in patients suffering from rheumatoid arthritis. Direct agonists like nicotine and GTS-1 have also demonstrated anti-inflammatory properties in models of sepsis and acute respiratory distress syndrome, as have acetylcholinesterase inhibitors like Galantamine and Physostigmine. Experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome indicates that immunomodulators have a protective role in patient outcomes. Dexamethasone is the only medication currently in use that has shown to improve clinical outcomes. This is likely due to the suppression of what is referred to as a cytokine storm, which is implicated in the lethality of viral pneumonia. Nicotine transdermal patch activates CAP and harvests its anti-inflammatory potential by means of an easily administered depot delivery mechanism. It could prove to be a promising, safe and inexpensive additional tool in the currently limited armamentarium at our disposal for management of COVID-19 induced acute hypoxic respiratory failure.
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Affiliation(s)
- Farrukh Ahmad
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
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Association between Environmental Tobacco Smoke Exposure and Adaptive Behavior in Individuals with Autism Spectrum Disorder. TOXICS 2022; 10:toxics10040189. [PMID: 35448450 PMCID: PMC9027185 DOI: 10.3390/toxics10040189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/09/2022] [Accepted: 04/11/2022] [Indexed: 11/17/2022]
Abstract
The study focuses on current issues of adaptive behavior in individuals with autism spectrum disorder (ASD) and on the possible risk factor of environmental tobacco smoke (ETS). Children examined at the Academic Research Center for Autism (ARCA) in Bratislava were involved in the study. The study sample included 84 children (71 boys) with ASD (average age 5.35 years) and a non-ASD group of 24 children (20 boys; average age 8.10 years). The “ETS Questionnaire” focused on the detection of parental smoking habits and other ETS exposures. The concentrations of cotinine in urine were measured by ELISA kit. A significant delay in adaptive behavior of children with ASD in comparison with the non-ASD group was identified. The significant differences were in adaptive behavior, communication, and everyday skills. Children with ASD were more likely to be exposed to ETS, especially in the household. Good agreement was found between objective and subjective ETS exposure indicators (kappa = 0.613). Self-reported exposure to ETS corresponded significantly with the median levels of urinary cotinine. In addition to evaluation and assessment of the quality of adaptive behavior, an important goal of further research should be to identify, investigate, and eliminate environmental factors that interfere with adaptive behavior.
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Duko B, Pereira G, Tait RJ, Betts K, Newnham J, Alati R. Prenatal tobacco and alcohol exposures and the risk of anxiety symptoms in young adulthood: A population-based cohort study. Psychiatry Res 2022; 310:114466. [PMID: 35219268 DOI: 10.1016/j.psychres.2022.114466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 01/18/2022] [Accepted: 02/19/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Epidemiological studies have linked prenatal tobacco and alcohol exposures to internalizing behaviours in children and adolescents with inconsistent findings. Dearth of epidemiological studies have investigated the associations with the risk of experiencing symptoms of anxiety in young adulthood. METHODS Study participants (N = 1190) were from the Raine Study, a population-based prospective birth cohort based in Perth, Western Australia. Data on prenatal tobacco and alcohol exposures were available for the first and third trimesters of pregnancy. Experiencing symptoms of anxiety in young adulthood at age 20 years was measured by a short form of the Depression Anxiety Stress Scale (DASS 21). Relative risk (RR) of experiencing symptoms of anxiety in young adulthood for prenatal tobacco and alcohol exposures were estimated with log binomial regression. RESULTS After adjusting for potential confounders, we observed increased risks of experiencing symptoms of anxiety in young adults exposed to prenatal tobacco in the first trimester [RR = 1.52, 95% CI: 1.12-2.06, p-value < 0.01] and third trimester [RR = 1.53, 95% CI: 1.10-2.13, p-value = 0.02]. However, we found insufficient statistical evidence for an association between first trimester [RR = 1.01, 95% CI: 0.76-1.22, p-value = 0.90] and third trimester [RR = 1.03, 95% CI: 0.80-1.34, p-value = 0.91] prenatal exposure to alcohol and the risk of experiencing symptoms of anxiety in young adults. There was a dose response association between prenatal tobacco exposure and increasing anxiety symptoms in offspring. CONCLUSION The findings of this study suggest that an association between prenatal tobacco exposure and risk of anxiety symptoms remains apparent into young adulthood.
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Affiliation(s)
- Bereket Duko
- Curtin School of Population Health, Curtin University, Kent Street, Bentley WA 6102, Australia.
| | - Gavin Pereira
- Curtin School of Population Health, Curtin University, Kent Street, Bentley WA 6102, Australia; Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway; enAble Institute, Curtin University, Kent Street, Bentley, Western Australia 6102, Australia
| | - Robert J Tait
- National Drug Research Institute, Faculty of Health Sciences, Curtin University, 7 Parker Place Building 609, Level 2 Technology Park, Bentley WA 6102, Australia
| | - Kim Betts
- Curtin School of Population Health, Curtin University, Kent Street, Bentley WA 6102, Australia
| | - John Newnham
- Division of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, The University of Western Australia, 17 Monash Ave, Nedlands WA 6009, Australia
| | - Rosa Alati
- Curtin School of Population Health, Curtin University, Kent Street, Bentley WA 6102, Australia; Institute for Social Sciences Research, The University of Queensland, 80 Meier's Rd, Indooroopilly, Queensland 4068 Australia
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Duko B, Pereira G, Tait RJ, Betts K, Newnham J, Alati R. Prenatal alcohol and tobacco exposures and the risk of cannabis use in offspring: Findings from a population-based cohort study. Neurotoxicol Teratol 2022; 90:107064. [PMID: 35007727 DOI: 10.1016/j.ntt.2022.107064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 01/05/2022] [Accepted: 01/05/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND There is a paucity of prospective longitudinal studies examining the associations between maternal use of alcohol and tobacco during pregnancy and the risk of cannabis use in offspring. The aim of this study was to examine the association between prenatal alcohol and tobacco exposures and offspring cannabis use. METHODS Data were from the Raine Study, a longitudinal prospective birth cohort based in Western Australia. Cannabis use at 17 years of age was measured with a self-reported questionnaire developed to capture risky behaviors in adolescents. Associations between prenatal alcohol and tobacco exposures and the risk of cannabis use in offspring were examined using log-binomial regression models, computing relative risk (RR). We also computed the E-values (E) to estimate the extent of unmeasured confounding. RESULTS After adjusting for potential confounders, we observed increased risks of cannabis use in offspring exposed to first trimester prenatal alcohol use (RR = 1.38, 95% CI: 1.09-1.75; E = 2.10, CI:1.40) and tobacco use (RR = 1.42, 95% CI: 1.08-1.86; E = 2.19, CI:1.37) as well as third trimester prenatal alcohol use (RR = 1.39, 95% CI: 1.09-1.79; E = 2.13, CI:1.40) and tobacco use (RR = 1.39, 95% CI: 1.09-1.79; E = 2.21, CI:1.34]. We also noted dose-response associations in which risk estimates in offspring increased with the level of exposures to prenatal alcohol and tobacco use. CONCLUSION These findings provide epidemiological evidence for effects of prenatal alcohol and tobacco exposures on offspring cannabis use. Although these results should be confirmed by other studies, the present study adds to the mounting evidence suggesting that women should be encouraged to abstain from alcohol and tobacco during pregnancy.
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Affiliation(s)
- Bereket Duko
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA 6102, Australia.
| | - Gavin Pereira
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA 6102, Australia; Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway
| | - Robert J Tait
- National Drug Research Institute, Faculty of Health Sciences, Curtin University, 7 Parker Place Building 609, Level 2 Technology Park, Bentley, WA 6102, Australia
| | - Kim Betts
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA 6102, Australia
| | - John Newnham
- Division of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, The University of Western Australia, 17 Monash Ave, Nedlands, WA 6009, Australia
| | - Rosa Alati
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA 6102, Australia; Institute for Social Sciences Research, The University of Queensland, 80 Meier's Rd, Indooroopilly, Queensland 4068, Australia
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12
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Lin IH, Yang L, Dalley JW, Tsai TH. Trans-placental transfer of nicotine: Modulation by organic cation transporters. Biomed Pharmacother 2021; 145:112489. [PMID: 34915670 DOI: 10.1016/j.biopha.2021.112489] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/21/2021] [Accepted: 11/30/2021] [Indexed: 01/10/2023] Open
Abstract
Nicotine is a highly addictive substance and harmful to the developing foetus. However, few studies have investigated the transporter mechanism responsible for regulating the transfer of nicotine across the blood-placental interface. A multiple in-vivo microdialysis system coupled to ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed to monitor simultaneously nicotine and cotinine in the blood, placenta, foetus, and amniotic fluid of pregnant rats. The pharmacological mechanism of nicotine transfer across the placenta was investigated by co-administering corticosterone, an inhibitor of organic cation transporters (OCTs) that partly mediate the exchange of nicotine across the placenta. The results revealed that intravenously administered nicotine (1 mg/kg) was rapidly metabolised to cotinine with a transformation ratio (AUCcotinine/AUCnicotine) of 0.67 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.12, 0.31 ± 0.05 in maternal blood, placenta, amniotic fluid, and foetus, respectively. The tissue transformation ratios (AUCtissue/AUCblood) were 0.83 ± 0.16, 0.65 ± 0.17, 0.57 ± 0.13 for nicotine, and 0.25 ± 0.06, 0.24 ± 0.12, 0.26 ± 0.04 for cotinine at placenta, amniotic fluid and foetus, respectively. Following the co-administration of corticosterone (2 mg/kg), the tissue transformation ratio of nicotine was significantly reduced in the placenta but was significantly increased in the foetus. Levels of cotinine were not significantly altered by the administration of corticosterone. These findings implicate OCT in mediating the transfer of nicotine across the blood-placenta barrier. Understanding the mechanism of nicotine transfer through the placenta may inform therapeutic strategies to lessen the exposure of the developing foetus to nicotine in the maternal bloodstream.
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Affiliation(s)
- I-Hsin Lin
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Ling Yang
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Jeffrey W Dalley
- Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK; Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, UK
| | - Tung-Hu Tsai
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK; Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan.
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13
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Shutta KH, Balasubramanian R, Huang T, Jha SC, Zeleznik OA, Kroenke CH, Tinker LF, Smoller JW, Casanova R, Tworoger SS, Manson JE, Clish CB, Rexrode KM, Hankinson SE, Kubzansky LD. Plasma metabolomic profiles associated with chronic distress in women. Psychoneuroendocrinology 2021; 133:105420. [PMID: 34597898 PMCID: PMC8547060 DOI: 10.1016/j.psyneuen.2021.105420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 09/10/2021] [Accepted: 09/12/2021] [Indexed: 11/19/2022]
Abstract
Several forms of chronic distress including anxiety and depression are associated with adverse cardiometabolic outcomes. Metabolic alterations may underlie these associations. Whether these forms of distress are associated with metabolic alterations even after accounting for comorbid conditions and other factors remains unclear. Using an agnostic approach, this study examines a broad range of metabolites in relation to chronic distress among women. For this cross-sectional study of chronic distress and 577 plasma metabolites, data are from different substudies within the Women's Health Initiative (WHI) and Nurses' Health Studies (NHSI, NHSII). Chronic distress was characterized by depressive symptoms and other depression indicators in the WHI and NHSII substudies, and by combined indicators of anxiety and depressive symptoms in the NHSI substudy. We used a two-phase discovery-validation framework, with WHI (N = 1317) and NHSII (N = 218) substudies in the discovery phase (identifying metabolites associated with distress) and NHSI (N = 558) substudy in the validation phase. A differential network analysis provided a systems-level assessment of metabolomic alterations under chronic distress. Analyses adjusted for potential confounders and mediators (demographics, comorbidities, medications, lifestyle factors). In the discovery phase, 46 metabolites were significantly associated with depression measures. In validation, six of these metabolites demonstrated significant associations with chronic distress after adjustment for potential confounders. Among women with high distress, we found lower gamma-aminobutyric acid (GABA), threonine, biliverdin, and serotonin and higher C16:0 ceramide and 3-methylxanthine. Our findings suggest chronic distress is associated with metabolomic alterations and provide specific targets for future study of biological pathways in chronic diseases.
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Affiliation(s)
- Katherine H Shutta
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, 010 Arnold House, 715 North Pleasant Street, Amherst, MA 01003, USA.
| | - Raji Balasubramanian
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, 010 Arnold House, 715 North Pleasant Street, Amherst, MA 01003, USA.
| | - Tianyi Huang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
| | - Shaili C Jha
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Oana A Zeleznik
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
| | - Candyce H Kroenke
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
| | - Lesley F Tinker
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
| | - Jordan W Smoller
- Department of Psychiatry and Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
| | | | - Shelley S Tworoger
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Cancer Epidemiology, Moffit Cancer Center, Tampa, FL, USA.
| | - JoAnn E Manson
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
| | - Clary B Clish
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
| | - Kathryn M Rexrode
- Harvard Medical School, Boston, MA, USA; Division of Women's Health, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
| | - Susan E Hankinson
- Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, 010 Arnold House, 715 North Pleasant Street, Amherst, MA 01003, USA.
| | - Laura D Kubzansky
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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14
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Iarkov A, Mendoza C, Echeverria V. Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson's Disease. Front Neurosci 2021; 15:665820. [PMID: 34616271 PMCID: PMC8488354 DOI: 10.3389/fnins.2021.665820] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 08/26/2021] [Indexed: 12/20/2022] Open
Abstract
Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the midbrain resulting in progressive impairment in cognitive and motor abilities. The physiological and molecular mechanisms triggering dopaminergic neuronal loss are not entirely defined. PD occurrence is associated with various genetic and environmental factors causing inflammation and mitochondrial dysfunction in the brain, leading to oxidative stress, proteinopathy, and reduced viability of dopaminergic neurons. Oxidative stress affects the conformation and function of ions, proteins, and lipids, provoking mitochondrial DNA (mtDNA) mutation and dysfunction. The disruption of protein homeostasis induces the aggregation of alpha-synuclein (α-SYN) and parkin and a deficit in proteasome degradation. Also, oxidative stress affects dopamine release by activating ATP-sensitive potassium channels. The cholinergic system is essential in modulating the striatal cells regulating cognitive and motor functions. Several muscarinic acetylcholine receptors (mAChR) and nicotinic acetylcholine receptors (nAChRs) are expressed in the striatum. The nAChRs signaling reduces neuroinflammation and facilitates neuronal survival, neurotransmitter release, and synaptic plasticity. Since there is a deficit in the nAChRs in PD, inhibiting nAChRs loss in the striatum may help prevent dopaminergic neurons loss in the striatum and its pathological consequences. The nAChRs can also stimulate other brain cells supporting cognitive and motor functions. This review discusses the cholinergic system as a therapeutic target of cotinine to prevent cognitive symptoms and transition to dementia in PD.
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Affiliation(s)
- Alexandre Iarkov
- Laboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile
| | - Cristhian Mendoza
- Laboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile
| | - Valentina Echeverria
- Laboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile.,Research & Development Service, Bay Pines VA Healthcare System, Bay Pines, FL, United States
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15
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Duko B, Pereira G, Tait RJ, Newnham J, Betts K, Alati R. Prenatal tobacco exposure and the risk of conduct disorder symptoms in offspring at the age of 14 years: Findings from the Raine Study. J Psychiatr Res 2021; 142:1-8. [PMID: 34304077 DOI: 10.1016/j.jpsychires.2021.07.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/30/2021] [Accepted: 07/18/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Emerging epidemiological evidence suggests that offspring born to mothers who smoked tobacco during pregnancy may have elevated risk of developing conduct disorder (CD) symptoms. We examined associations between maternal and paternal tobacco smoking during pregnancy and CD symptoms in offspring at the age of 14 years. METHODS We obtained data from the Raine Study, a multi-generational cohort study based in Western Australia. DSM-oriented scale of the Child Behavior Checklist (CBCL) was used to measure CD symptoms in offspring. Negative binomial regression was used to estimate the rate ratio (risks) (RR) of CD symptoms in offspring. We also produced the E-values to investigate the extent of unmeasured confounding. Paternal smoking during pregnancy was used as a proxy for environmental tobacco smoke exposure. RESULTS Complete data were available for 1747 mother-offspring and 1711 father-offspring pairs. After adjusting for potential confounders, we found elevated risks (rates) of CD symptoms in offspring born to mothers smoking tobacco during the first trimester [RR 1.52 (95 % CI: 1.24-1.87)], third trimester [RR 1.36 (95 % CI: 1.09-1.69)] and during both trimesters of pregnancy [RR 1.50 (95 % CI: 1.19-1.90)]. The rates of CD symptoms in offspring increased with the level of exposure to maternal smoking during pregnancy. However, we noted insufficient statistical evidence for an association between paternal smoking during pregnancy and CD symptoms in offspring. CONCLUSION The associations we found for maternal but not paternal smoking may suggest a biological mechanism for intrauterine tobacco exposure on the risk of CD symptoms in offspring. Early interventions assisting pregnant mothers to quit tobacco smoking, or avoid smoking initiation, have potential to contribute health benefits to both mothers and their offspring.
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Affiliation(s)
- Bereket Duko
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA, 6102, Australia.
| | - Gavin Pereira
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA, 6102, Australia; Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway
| | - Robert J Tait
- National Drug Research Institute, Faculty of Health Sciences, Curtin University, 7 Parker Place Building 609, Level 2 Technology Park, Bentley, WA, 6102, Australia
| | - John Newnham
- Division of Obstetrics and Gynaecology, Faculty of Health and Medical Sciences, The University of Western Australia, 17 Monash Ave, Nedlands, WA, 6009, Australia
| | - Kim Betts
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA, 6102, Australia
| | - Rosa Alati
- Curtin School of Population Health, Curtin University, Kent Street, Bentley, WA, 6102, Australia; Institute for Social Sciences Research, The University of Queensland, 80 Meier's Rd, Indooroopilly, Queensland, 4068, Australia
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16
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Wu CC, Wang HE, Liu YC, Zheng CM, Chu P, Lu KC, Chu CM, Chang YT. Sleeping, Smoking, and Kidney Diseases: Evidence From the NHANES 2017-2018. Front Med (Lausanne) 2021; 8:745006. [PMID: 34651001 PMCID: PMC8505692 DOI: 10.3389/fmed.2021.745006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/30/2021] [Indexed: 12/23/2022] Open
Abstract
Study Objectives: Smoking and sleep are modifiable factors associated with the chronic kidney diseases. However, the interaction of smoking and sleep on the renal function are still unclear. Therefore, we aimed to evaluate the interactive impacts of smoking and sleep on the renal function. Methods: Data were obtained from the National Health and Nutrition Examination Survey. The study population were categorized into nine subgroups by smoking (smoking every day, sometimes, and non-smokers recently) and sleep duration (short duration ≤ 6 h, normal duration 6-9 h, and longer duration ≥ 9 h on the weekdays). Results: The study group with a short sleep duration had significantly higher serum cotinine and hydrocotinine levels compared with the other two sleep groups. After adjusting the demographic characteristics (age, race, body mass index, and marital status), sleep quality (snoring or breathing cessation), and comorbidities (diabetes mellitus, hypertension, high cholesterol, anemia, congestive heart failure, coronary heart disease, and stroke), non-smokers with short or long sleep duration had significant lower estimated glomerular filtration rate (eGFR) levels than the study group who smoked every day and slept ≤ 6 h. The effects of sleep duration on eGFR levels varied with smoking status. For the study group smoking every day, eGFR levels increased as sleep duration decreased, whereas for the study group smoking sometimes, eGFR levels increased as sleep duration increased. The U-shaped effects of eGFR levels were observed among non-smokers whose normal sleep duration was associated with better eGFR levels. Normal sleep duration was an important protective factor of the renal function for non-smokers than smokers. Conclusions: The effects of sleep duration on eGFR levels varied with smoking status. Normal sleep duration was a protective factor and more crucial for non-smokers than for smokers.
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Affiliation(s)
- Chia-Chao Wu
- Division of Nephrology, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
- National Defense Medical Center, Department and Graduate Institute of Microbiology and Immunology, Taipei, Taiwan
| | - Han-En Wang
- Division of Nephrology, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
| | - Yi-Chun Liu
- School of Public Health, National Defense Medical Center, Taipei City, Taiwan
| | - Cai-Mei Zheng
- Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- TMU Research Centre of Urology and Kidney, Taipei Medical University, Taipei, Taiwan
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Pauling Chu
- Division of Nephrology, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
| | - Kuo-Cheng Lu
- Division of Nephrology, Department of Medicine, School of Medicine, Fu-Jen Catholic Hospital, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chi-Ming Chu
- School of Public Health, National Defense Medical Center, Taipei City, Taiwan
- Department of Surgery, National Defense Medical Center, Songshan Branch of Tri-Service General Hospital, Taipei City, Taiwan
- Division of Biostatistics and Informatics, Department of Epidemiology, National Defense Medical Center, School of Public Health, Taipei, Taiwan
- Department of Public Health, China Medical University, Taichung City, Taiwan
- Department of Public Health, Kaohsiung Medical University, Kaohsiung City, Taiwan
| | - Yu-Tien Chang
- School of Public Health, National Defense Medical Center, Taipei City, Taiwan
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Jamieson CS, Misa J, Tang Y, Billingsley JM. Biosynthesis and synthetic biology of psychoactive natural products. Chem Soc Rev 2021; 50:6950-7008. [PMID: 33908526 PMCID: PMC8217322 DOI: 10.1039/d1cs00065a] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Psychoactive natural products play an integral role in the modern world. The tremendous structural complexity displayed by such molecules confers diverse biological activities of significant medicinal value and sociocultural impact. Accordingly, in the last two centuries, immense effort has been devoted towards establishing how plants, animals, and fungi synthesize complex natural products from simple metabolic precursors. The recent explosion of genomics data and molecular biology tools has enabled the identification of genes encoding proteins that catalyze individual biosynthetic steps. Once fully elucidated, the "biosynthetic pathways" are often comparable to organic syntheses in elegance and yield. Additionally, the discovery of biosynthetic enzymes provides powerful catalysts which may be repurposed for synthetic biology applications, or implemented with chemoenzymatic synthetic approaches. In this review, we discuss the progress that has been made toward biosynthetic pathway elucidation amongst four classes of psychoactive natural products: hallucinogens, stimulants, cannabinoids, and opioids. Compounds of diverse biosynthetic origin - terpene, amino acid, polyketide - are identified, and notable mechanisms of key scaffold transforming steps are highlighted. We also provide a description of subsequent applications of the biosynthetic machinery, with an emphasis placed on the synthetic biology and metabolic engineering strategies enabling heterologous production.
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Affiliation(s)
- Cooper S Jamieson
- Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.
| | - Joshua Misa
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
| | - Yi Tang
- Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA. and Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
| | - John M Billingsley
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA. and Invizyne Technologies, Inc., Monrovia, CA, USA
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Boiangiu RS, Mihasan M, Gorgan DL, Stache BA, Hritcu L. Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish ( Danio rerio) Model of Alzheimer's Disease. Antioxidants (Basel) 2021; 10:212. [PMID: 33535660 PMCID: PMC7912787 DOI: 10.3390/antiox10020212] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/18/2021] [Accepted: 01/27/2021] [Indexed: 12/20/2022] Open
Abstract
Cotinine (COT) and 6-hydroxy-L-nicotine (6HLN) are two nicotinic derivatives that possess cognitive-improving abilities and antioxidant properties in different rodent models of Alzheimer's disease (AD), eluding the side-effects of nicotine (NIC), the parent molecule. In the current study, we evaluated the impact of COT and 6HLN on memory deterioration, anxiety, and oxidative stress in the scopolamine (SCOP)-induced zebrafish model of AD. For this, COT and 6HLN were acutely administered by immersion to zebrafish that were treated with SCOP before testing. The memory performances were assessed in Y-maze and object discrimination (NOR) tasks, while the anxiety-like behavior was evaluated in the novel tank diving test (NTT). The acetylcholinesterase (AChE) activity and oxidative stress were measured from brain samples. The RT-qPCR analysis was used to evaluate the npy, egr1, bdnf, and nrf2a gene expression. Our data indicated that both COT and 6HLN attenuated the SCOP-induced anxiety-like behavior and memory impairment and reduced the oxidative stress and AChE activity in the brain of zebrafish. Finally, RT-qPCR analysis indicated that COT and 6HLN increased the npy, egr1, bdnf, and nrf2a gene expression. Therefore, COT and 6HLN could be used as tools for improving AD conditions.
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Affiliation(s)
- Razvan Stefan Boiangiu
- Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700506 Iasi, Romania; (M.M.); (D.L.G.); (B.A.S.)
| | | | | | | | - Lucian Hritcu
- Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, 700506 Iasi, Romania; (M.M.); (D.L.G.); (B.A.S.)
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Bulló M, Papandreou C, Ruiz-Canela M, Guasch-Ferré M, Li J, Hernández-Alonso P, Toledo E, Liang L, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Arós F, Fiol M, Serra-Majem L, Clish CB, Becerra-Tomás N, Martínez-González MA, Hu FB, Salas-Salvadó J. Plasma Metabolomic Profiles of Glycemic Index, Glycemic Load, and Carbohydrate Quality Index in the PREDIMED Study. J Nutr 2021; 151:50-58. [PMID: 33296468 PMCID: PMC7779218 DOI: 10.1093/jn/nxaa345] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/10/2020] [Accepted: 10/07/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The quality of carbohydrate consumed, assessed by the glycemic index (GI), glycemic load (GL), or carbohydrate quality index (CQI), affects the postprandial glycemic and insulinemic responses, which have been implicated in the etiology of several chronic diseases. However, it is unclear whether plasma metabolites involved in different biological pathways could provide functional insights into the role of carbohydrate quality indices in health. OBJECTIVES We aimed to identify plasma metabolomic profiles associated with dietary GI, GL, and CQI. METHODS The present study is a cross-sectional analysis of 1833 participants with overweight/obesity (mean age = 67 y) from 2 case-cohort studies nested within the PREDIMED (Prevención con Dieta Mediterránea) trial. Data extracted from validated FFQs were used to estimate the GI, GL, and CQI. Plasma concentrations of 385 metabolites were profiled with LC coupled to MS and associations of these metabolites with those indices were assessed with elastic net regression analyses. RESULTS A total of 58, 18, and 57 metabolites were selected for GI, GL, and CQI, respectively. Choline, cotinine, γ-butyrobetaine, and 36:3 phosphatidylserine plasmalogen were positively associated with GI and GL, whereas they were negatively associated with CQI. Fructose-glucose-galactose was negatively and positively associated with GI/GL and CQI, respectively. Consistent associations of 21 metabolites with both GI and CQI were found but in opposite directions. Negative associations of kynurenic acid, 22:1 sphingomyelin, and 38:6 phosphatidylethanolamine, as well as positive associations of 32:1 phosphatidylcholine with GI and GL were also observed. Pearson correlation coefficients between GI, GL, and CQI and the metabolomic profiles were 0.30, 0.22, and 0.27, respectively. CONCLUSIONS The GI, GL, and CQI were associated with specific metabolomic profiles in a Mediterranean population at high cardiovascular disease risk. Our findings may help in understanding the role of dietary carbohydrate indices in the development of cardiometabolic disorders. This trial was registered at isrctn.com as ISRCTN35739639.
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Affiliation(s)
- Mònica Bulló
- Universitat Rovira i Virgili, Biochemistry and Biotechnology Department, Human Nutrition Unit, Reus, Spain
- Pere i Virgili Health Research Institute (IISPV), Reus, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
| | - Christopher Papandreou
- Universitat Rovira i Virgili, Biochemistry and Biotechnology Department, Human Nutrition Unit, Reus, Spain
- Pere i Virgili Health Research Institute (IISPV), Reus, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
| | - Miguel Ruiz-Canela
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Navarra, Spain
| | - Marta Guasch-Ferré
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Jun Li
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Pablo Hernández-Alonso
- Universitat Rovira i Virgili, Biochemistry and Biotechnology Department, Human Nutrition Unit, Reus, Spain
- Pere i Virgili Health Research Institute (IISPV), Reus, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), Malaga, Spain
| | - Estefania Toledo
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Navarra, Spain
| | - Liming Liang
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Statistics, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Cristina Razquin
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Navarra, Spain
| | - Dolores Corella
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Ramon Estruch
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Internal Medicine, Hospital Clínic, University of Barcelona, Barcelona, Spain
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Emilio Ros
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
- Lipid Clinic, Department of Endocrinology and Nutrition, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Montserrat Fitó
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Cardiovascular and Nutrition Research Group, Hospital del Mar Medical Research Institute, Barcelona, Spain
| | - Fernando Arós
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Cardiology, University Hospital of Alava, Vitoria, Spain
| | - Miquel Fiol
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain
| | - Lluís Serra-Majem
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Las Palmas, Spain
| | - Clary B Clish
- Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA
| | - Nerea Becerra-Tomás
- Universitat Rovira i Virgili, Biochemistry and Biotechnology Department, Human Nutrition Unit, Reus, Spain
- Pere i Virgili Health Research Institute (IISPV), Reus, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
| | - Miguel A Martínez-González
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, Navarra, Spain
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Frank B Hu
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA
- Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jordi Salas-Salvadó
- Universitat Rovira i Virgili, Biochemistry and Biotechnology Department, Human Nutrition Unit, Reus, Spain
- Pere i Virgili Health Research Institute (IISPV), Reus, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain
- Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain
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Developmental impaired Akt signaling in the Shank1 and Shank3 double knock-out mice. Mol Psychiatry 2021; 26:1928-1944. [PMID: 33402706 PMCID: PMC8440179 DOI: 10.1038/s41380-020-00979-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 11/23/2020] [Accepted: 12/01/2020] [Indexed: 01/30/2023]
Abstract
Human mutations and haploinsufficiency of the SHANK family genes are associated with autism spectrum disorders (ASD) and intellectual disability (ID). Complex phenotypes have been also described in all mouse models of Shank mutations and deletions, consistent with the heterogeneity of the human phenotypes. However, the specific role of Shank proteins in synapse and neuronal functions remain to be elucidated. Here, we generated a new mouse model to investigate how simultaneously deletion of Shank1 and Shank3 affects brain development and behavior in mice. Shank1-Shank3 DKO mice showed a low survival rate, a developmental strong reduction in the activation of intracellular signaling pathways involving Akt, S6, ERK1/2, and eEF2 during development and a severe behavioral impairments. Our study suggests that Shank1 and Shank3 proteins are essential to developmentally regulate the activation of Akt and correlated intracellular pathways crucial for mammalian postnatal brain development and synaptic plasticity. Therefore, Akt function might represent a new therapeutic target for enhancing cognitive abilities of syndromic ASD patients.
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Lin SX, Curtis MA, Sperry J. Pyridine alkaloids with activity in the central nervous system. Bioorg Med Chem 2020; 28:115820. [PMID: 33120080 PMCID: PMC7561606 DOI: 10.1016/j.bmc.2020.115820] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 09/27/2020] [Accepted: 10/05/2020] [Indexed: 12/29/2022]
Abstract
This review discusses all pyridine alkaloids with CNS activity, their therapeutic potential, and the interesting array of sources whence they originate.
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Affiliation(s)
- Simon X Lin
- School of Chemical Sciences, University of Auckland, Auckland, New Zealand
| | - Maurice A Curtis
- Centre for Brain Research, University of Auckland, Auckland, New Zealand; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand
| | - Jonathan Sperry
- School of Chemical Sciences, University of Auckland, Auckland, New Zealand.
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Effect of Sample Storage Conditions on Measurements of Salivary Cotinine Levels. Metabolites 2020; 10:metabo10090365. [PMID: 32911758 PMCID: PMC7569849 DOI: 10.3390/metabo10090365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 08/21/2020] [Accepted: 09/06/2020] [Indexed: 11/17/2022] Open
Abstract
Information on smoking exposure obtained with self-reports may be inaccurate. Cotinine has a large half-life and its salivary levels correlate well with plasmatic levels. The influence of storage conditions on the validity and precision of salivary cotinine assessments has rarely been evaluated. Here, smokers donated saliva samples, which were sent for immediate analysis, mail posting, storage at 4 °C for 30 or 90 days, or storage at −20 °C for 30 or 90 days. Cotinine levels were determined using enzyme-linked immune-sorbent assay. Agreement of cotinine level measurements was assessed using Bland-Altman analyses. Average age (years), duration of smoking (years) and number of cigarettes smoked (/day) were 55.4 (±SD 9.4), 35.1 (±SD 11.3), and 15.3 (±SD 7.6). The mean immediate cotinine level was 457 ng/mL (range 11.3 to 1318 ng/mL). Mean cotinine levels in samples analyzed after delay ranged between 433 ng/mL (−20 °C 30 days) and 468 ng/mL (4 °C 30 days). A dose-response gradient was observed in the relationship between salivary cotinine level and self-reported smoking status. A good agreement between cotinine levels for all storage conditions compared with immediate analysis was observed, with average differences ranging from −11 to 24 ng/mL. Cotinine levels remained stable regardless of the tested condition. The stability of salivary cotinine may enable samples to be obtained in difficult-to-reach areas, reduce study costs, and improve the validity of the information on exposure to smoking.
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Sadigh-Eteghad S, Vatandoust SM, Mahmoudi J, Rahigh Aghsan S, Majdi A. Cotinine ameliorates memory and learning impairment in senescent mice. Brain Res Bull 2020; 164:65-74. [PMID: 32818583 DOI: 10.1016/j.brainresbull.2020.08.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/29/2020] [Accepted: 08/10/2020] [Indexed: 10/23/2022]
Abstract
This study aimed to assess the effects of cotinine on age-induced memory and learning impairment and related downstream pathways in mice. Thirty aged (18-month old) and 10 young mice (8-week old) were randomly divided into 4 groups (n = 10 each) and subjected to cotinine at 5 mg/kg dose and/or methyllycaconitine (MLA) at 1 mg/kg, i.p. dose (α7 nAChRs antagonist) for 4 weeks. Morris water maze (MWM) and novel object recognition (NOR) tasks were used to assess spatial and recognition learning and memories of the mice, respectively. Levels of oxidative stress, apoptosis, neuroinflammation, and structural synaptic plasticity, and also neurotrophic factors and α7 nAChRs were assessed in the hippocampus using either ELISA or Western blotting. Aging was associated with learning and memory disabilities and dysregulation of the assessed pathways in the hippocampus of mice. Chronic cotinine treatment improved learning and memory in aged animals, indicated by decreased latency time, and increased time spent in the target quadrant and discrimination index (DI) in the MWM and NOR tasks. Also, chronic cotinine injection increased total antioxidant capacity (TAC), SOD and GSH-px activity, PSD-95, GAP-43, SYN, brain-derived neurotrophic factor, and neural growth factor levels and decreased malondialdehyde, TNF-α, and IL-1β in the hippocampus of aged mice. Conversely, MLA treatment reversed most of the mentioned effects via the blockade of α7 nAChRs. Cotinine improves age-induced memory and learning impairment via its modulatory effects on α7 nAChRs and subsequent activation/deactivation of the mentioned pathways in the hippocampus of aged mice.
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Affiliation(s)
- Saeed Sadigh-Eteghad
- Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Mehdi Vatandoust
- Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Mahmoudi
- Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sepideh Rahigh Aghsan
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Majdi
- Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
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Rosa MB, Fernandes MDS, Bonjardim LR, Gavião MBD, Calixto LA, Castelo PM. Evaluation of oral mechanical and gustatory sensitivities and salivary cotinine levels in adult smokers. Acta Odontol Scand 2020; 78:256-264. [PMID: 31775545 DOI: 10.1080/00016357.2019.1694978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 10/25/2019] [Accepted: 11/15/2019] [Indexed: 10/25/2022]
Abstract
Objective: The aim was to examine oral mechanical and gustatory sensitivities in adult smokers and to estimate salivary levels of cotinine by tobacco consumption. A total of 54 adults (20-45 years old; 28 males/26 females) were divided into two sex-paired groups: smoker group (n = 27), tobacco consumers with no other chronic disease/use of chronic medication, and a control non-smoker non-exposed group with similar age (n = 27).Materials and Methods: 24 h-Recall was used to gather information about tobacco consumption, date of onset and duration of the habit. Oral mechanical evaluation comprised touch detection threshold (MDT) of upper and lower lips and tongue tip and two-point discrimination (TPD) assessments. Taste sensitivities for sweet, salty, sour and bitter were evaluated in four concentrations. Salivary cotinine was determined by high performance liquid chromatography. Statistical analysis comprised Mann-Whitney, Two-way ANOVA test and regression analysis.Results: The mean smoking time was 13.6 years (mean 8.4 mg/day; 13 cigarettes/day). A sex-effect was observed on MDT of tongue tip (higher sensitivity in females), while group-effect was observed on TPD of lower lip, showing a smaller sensitivity among smokers (p < .05; moderate effect: Eta partial2 = 0.076). Although the total score of gustatory sensitivity did not differ between groups, smokers exhibited an irregular pattern of correctly identified tastants among the different concentrations of salty, sour and bitter. The predictive model showed that salivary cotinine was dependent on "nicotine consumption on the day before" (R2 = 49%).Conclusion: A difference in tactile sensitivity of the lower lip and qualitative changes in taste sensitivity were observed in smokers.
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Affiliation(s)
| | | | | | | | - Leandro Augusto Calixto
- Department Pharmaceutical Sciences, Universidade Federal de São Paulo (UNIFESP), Diadema, Brazil
| | - Paula Midori Castelo
- Department Pharmaceutical Sciences, Universidade Federal de São Paulo (UNIFESP), Diadema, Brazil
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25
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Ciocan RA, Cătană CS, Drugan C, Gherman CD, Ciocan A, Drugan TC, Bolboacă SD. Relation between serum cotinine levels and trophic lesions in patients with critical limb ischemia: a pilot study. Acta Clin Belg 2020; 75:149-154. [PMID: 30741123 DOI: 10.1080/17843286.2019.1577530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.
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Affiliation(s)
- Răzvan A. Ciocan
- Department of Medical Informatics and Biostatistics, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
- Department of Vascular Surgery, Second Surgical Clinic, Emergency County Hospital Cluj-Napoca, Cluj-Napoca, Romania
| | - Cristina-Sorina Cătană
- Department of Medical Biochemistry, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Cristina Drugan
- Department of Medical Biochemistry, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Claudia D. Gherman
- Department of Vascular Surgery, Second Surgical Clinic, Emergency County Hospital Cluj-Napoca, Cluj-Napoca, Romania
- Department of Practical Skills, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Andra Ciocan
- Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Tudor C. Drugan
- Department of Medical Informatics and Biostatistics, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Sorana D. Bolboacă
- Department of Medical Informatics and Biostatistics, Iuliu Haţieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
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Iarkov A, Barreto GE, Grizzell JA, Echeverria V. Strategies for the Treatment of Parkinson's Disease: Beyond Dopamine. Front Aging Neurosci 2020; 12:4. [PMID: 32076403 PMCID: PMC7006457 DOI: 10.3389/fnagi.2020.00004] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 01/09/2020] [Indexed: 12/11/2022] Open
Abstract
Parkinson’s disease (PD) is the second-leading cause of dementia and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra alongside the presence of intraneuronal α-synuclein-positive inclusions. Therapies to date have been directed to the restoration of the dopaminergic system, and the prevention of dopaminergic neuronal cell death in the midbrain. This review discusses the physiological mechanisms involved in PD as well as new and prospective therapies for the disease. The current data suggest that prevention or early treatment of PD may be the most effective therapeutic strategy. New advances in the understanding of the underlying mechanisms of PD predict the development of more personalized and integral therapies in the years to come. Thus, the development of more reliable biomarkers at asymptomatic stages of the disease, and the use of genetic profiling of patients will surely permit a more effective treatment of PD.
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Affiliation(s)
- Alexandre Iarkov
- Laboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile
| | - George E Barreto
- Department of Biological Sciences, University of Limerick, Limerick, Ireland.,Health Research Institute, University of Limerick, Limerick, Ireland
| | - J Alex Grizzell
- Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, CO, United States
| | - Valentina Echeverria
- Laboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, Chile.,Research & Development Service, Bay Pines VA Healthcare System, Bay Pines, FL, United States
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27
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Merecz-Sadowska A, Sitarek P, Zielinska-Blizniewska H, Malinowska K, Zajdel K, Zakonnik L, Zajdel R. A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment. Int J Mol Sci 2020; 21:ijms21020652. [PMID: 31963832 PMCID: PMC7013895 DOI: 10.3390/ijms21020652] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 01/03/2020] [Accepted: 01/15/2020] [Indexed: 12/11/2022] Open
Abstract
Worldwide use of electronic cigarettes has been rapidly expanding over recent years, but the long-term effect of e-cigarette vapor exposure on human health and environment is not well established; however, its mechanism of action entails the production of reactive oxygen species and trace metals, and the exacerbation of inflammation, which are associated with potential cytotoxicity and genotoxicity. The present study examines the effects of selected liquid chemicals used in e-cigarettes, such as propylene glycol/vegetable glycerin, nicotine and flavorings, on living organisms; the data collected indicates that exposure to e-cigarette liquid has potentially detrimental effects on cells in vitro, and on animals and humans in vivo. While e-liquid exposure can adversely influence the physiology of living organisms, vaping is recommended as an alternative for tobacco smoking. The study also compares the impact of e-cigarette liquid exposure and traditional cigarette smoke on organisms and the environmental impact. The environmental influence of e-cigarette use is closely connected with the emission of airborne particulate matter, suggesting the possibility of passive smoking. The obtained data provides an insight into the impact of nicotine delivery systems on living organisms and the environment.
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Affiliation(s)
- Anna Merecz-Sadowska
- Department of Economic Informatics, University of Lodz, 90-214 Lodz, Poland; (K.M.); (L.Z.); (R.Z.)
- Correspondence: ; Tel.: +48-663-626-667
| | - Przemyslaw Sitarek
- Department of Biology and Pharmaceutical Botany, Medical University of Lodz, 90-151 Lodz, Poland;
| | | | - Katarzyna Malinowska
- Department of Economic Informatics, University of Lodz, 90-214 Lodz, Poland; (K.M.); (L.Z.); (R.Z.)
- Department of Allergology and Respiratory Rehabilitation, Medical University of Lodz, 90-725 Lodz, Poland;
| | - Karolina Zajdel
- Department of Medical Informatics and Statistics, Medical University of Lodz, 90-645 Lodz, Poland;
| | - Lukasz Zakonnik
- Department of Economic Informatics, University of Lodz, 90-214 Lodz, Poland; (K.M.); (L.Z.); (R.Z.)
| | - Radoslaw Zajdel
- Department of Economic Informatics, University of Lodz, 90-214 Lodz, Poland; (K.M.); (L.Z.); (R.Z.)
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Polli FS, Kohlmeier KA. Prenatal Nicotine Exposure in Rodents: Why Are There So Many Variations in Behavioral Outcomes? Nicotine Tob Res 2019; 22:1694-1710. [DOI: 10.1093/ntr/ntz196] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/05/2019] [Indexed: 01/01/2023]
Abstract
Abstract
Introduction
The World Health Organization (WHO) reported that smoking cessation rates among women have stagnated in the past decade and estimates that hundreds of millions of women will be smokers in the next decade. Social, environmental, and biological conditions render women more susceptible to nicotine addiction, imposing additional challenges to quit smoking during gestation, which is likely why more than 8% of pregnancies in Europe are associated with smoking. In epidemiological investigations, individuals born from gestational exposure to smoking exhibit a higher risk of development of attention-deficit/hyperactive disorder (ADHD) and liability to drug dependence. Among other teratogenic compounds present in tobacco smoke, nicotine actions during neuronal development could contribute to the observed outcomes as nicotine misleads signaling among progenitor cells during brain development. Several experimental approaches have been developed to address the consequences of prenatal nicotine exposure (PNE) to the brain and behavior but, after four decades of studies, inconsistent data have been reported and the lack of consensus in the field has compromised the hypothesis that gestational nicotine exposure participates in cognitive and emotional behavioral deficits.
Aims
In this review, we discuss the most commonly used PNE models with focus on their advantages and disadvantages, their relative validity, and how the different technical approaches could play a role in the disparate outcomes.
Results
We propose methodological considerations, which could improve the translational significance of the PNE models.
Conclusions
Such alterations might be helpful in reconciling experimental findings, as well as leading to development of treatment targets for maladaptive behaviors in those prenatally exposed.
Implications
In this article, we have reviewed the advantages and disadvantages of different variables of the commonly used experimental models of PNE. We discuss how variations in the nicotine administration methods, the timing of nicotine exposure, nicotine doses, and species employed could contribute to the disparate findings in outcomes for PNE offspring, both in behavior and neuronal changes. In addition, recent findings suggest consideration of epigenetic effects extending across generations. Finally, we have suggested improvements in the available PNE models that could contribute to the enhancement of their validity, which could assist in the reconciliation of experimental findings.
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Affiliation(s)
- Filip Souza Polli
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Kristi Anne Kohlmeier
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Ironside N, Chen CJ, Pucci J, Connolly ES. Effect of Cigarette Smoking on Functional Outcomes in Patients with Spontaneous Intracerebral Hemorrhage. J Stroke Cerebrovasc Dis 2019; 28:2496-2505. [PMID: 31279697 DOI: 10.1016/j.jstrokecerebrovasdis.2019.06.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 04/25/2019] [Accepted: 06/08/2019] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Nicotine may have neuroprotective effects on the injured brain through modulation of the cholinergic anti-inflammatory pathway. AIMS This study aimed to evaluate the relationship between cigarette smoking and outcomes in patients with spontaneous intracerebral hemorrhage (ICH). METHODS This was a retrospective review of consecutive ICH patients enrolled in the ICH Outcomes Project from 2009 to 2017. Patients with age ≥18 years and baseline modified Rankin Scale (mRS) score 0-2 were included. Smoking patterns were categorized as recent smoker (≤30 days prior to ICH) and not recent smoker (>30 days prior to ICH). Not recent smokers were further categorized into former smokers and nonsmokers. The primary outcome was good outcome (90-day mRS ≤ 2). Secondary outcomes were excellent outcome (90-day mRS 0-1), 90-day Barthel Index, and in-hospital and 90-day mortality. RESULTS The study cohort comprised 545 patients, including 60 recent smokers and 485 not recent smokers. Recent smokers had higher rates of good (35% versus 23%; odds ratio [OR] = 1.787, P = .047) and excellent (25% versus 13%; OR = 2.220, P = .015) outcomes compared to not recent smokers. These differences were not significant after baseline adjustments. Recent smokers had higher rates of good (36% versus 24%; OR = 1.732, P = .063) and excellent (25% versus 13%; OR = 2.203, P = .018) outcomes compared to nonsmokers. These differences were not significant after baseline adjustments. A 90-day Barthel Index, in-hospital, and 90-day mortality were comparable between recent and not recent smokers, recent and nonsmokers, and former and nonsmokers. CONCLUSIONS Despite potential neuroprotective effects of nicotine found in cigarettes, these may be outweighed by the detrimental effects of cigarette smoking on health outcomes.
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Affiliation(s)
- Natasha Ironside
- Department of Neurological Surgery, Columbia University Medical Center, New York, New York.
| | - Ching-Jen Chen
- Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia
| | - Josephine Pucci
- Department of Neurological Surgery, Columbia University Medical Center, New York, New York
| | - Edward Sander Connolly
- Department of Neurological Surgery, Columbia University Medical Center, New York, New York
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Terzioglu F, Boztepe H, Erkekoglu P, Er Korucu A, Kocer-Gumusel B, Kandemir O. The effects of amniotic fluid and foetal cord blood cotinine concentrations on pregnancy complications and the anthropometric measurements of newborns. J OBSTET GYNAECOL 2019; 39:952-958. [PMID: 31215267 DOI: 10.1080/01443615.2019.1599834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Our objective was determining the effects of amniotic fluid (AF) and fetal cord blood (FCB) cotinine concentrations on pregnancy complications and the anthropometric measurements in the newborns whose mothers underwent amniocentesis. This study was conducted as a case-control study, in Turkey. A total of 250 pregnant women with amniocentesis indication were recruited into the study and the cotinine levels in the AF and FCB were determined. A smoking habit did not statistically affect the incidence of pregnancy complications (p>.05). The birth weights of the newborns were negatively correlated with the AF cotinine levels. The incidences of low birth weight, low Apgar scores and RDS were positively correlated with higher levels of cotinine in AF and FCB. It is important for healthcare staff to provide training and consultancy services for the health improvement of pregnant women and the prevention of smoking during pregnancy. Impact statement What is already known on this subject? The pre-pregnancy smoking habit usually continues during the pregnancy. A significant negative correlation was present between the foetal cord blood cotinine levels and the birth weight. What do the results of this study add? The anthropometric measurements of the newborns born from mothers with high AF cotinine levels were lower than newborns born from mothers with low amniotic fluid cotinine levels. Respiratory Distress syndrome is more often determined in newborns born from mothers with high AF cotinine levels. What are the implications of these findings for clinical practice and/or further research? Future studies should be performed to investigate the effects of cigarette smoking on the health problems, the growth characteristics and the neurological development of newborns and infants within the first year of life.
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Affiliation(s)
- Fusun Terzioglu
- Department of Nursing, Faculty of Health Sciences, Atilim University , Ankara , Turkey
| | - Handan Boztepe
- Faculty of Nursing, Hacettepe University , Ankara , Turkey
| | - Pinar Erkekoglu
- Department of Toxicology, Faculty of Pharmacy, Hacettepe University , Ankara , Turkey
| | - Aslı Er Korucu
- Department of Midwifery, Faculty of Nursing, Ankara University , Ankara , Turkey
| | - Belma Kocer-Gumusel
- Department of Toxicology, Faculty of Pharmacy, Lokman Hekim University , Ankara , Turkey
| | - Omer Kandemir
- Zübeyde Hanım Etlik Woman Health and Disease, Teaching and Research Hospital , Ankara , Turkey
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Papandreou C, Hernández-Alonso P, Bulló M, Ruiz-Canela M, Yu E, Guasch-Ferré M, Toledo E, Dennis C, Deik A, Clish C, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Arós F, Fiol M, Lapetra J, Ruano C, Liang L, Martínez-González MA, Hu FB, Salas-Salvadó J. Plasma Metabolites Associated with Coffee Consumption: A Metabolomic Approach within the PREDIMED Study. Nutrients 2019; 11:E1032. [PMID: 31072000 PMCID: PMC6566346 DOI: 10.3390/nu11051032] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/02/2019] [Accepted: 05/03/2019] [Indexed: 02/07/2023] Open
Abstract
Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56-0.64), 0.78 (95% CI 0.75-0.81) and 0.52 (95% CI 0.49-0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.
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Affiliation(s)
- Christopher Papandreou
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201 Reus, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Pablo Hernández-Alonso
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201 Reus, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Mònica Bulló
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201 Reus, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Miguel Ruiz-Canela
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- University of Navarra, Department of Preventive Medicine and Public Health, IdiSNA, 31009 Pamplona, Spain.
| | - Edward Yu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Marta Guasch-Ferré
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201 Reus, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Estefanía Toledo
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- University of Navarra, Department of Preventive Medicine and Public Health, IdiSNA, 31009 Pamplona, Spain.
| | - Courtney Dennis
- Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
| | - Amy Deik
- Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
| | - Clary Clish
- Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
| | - Cristina Razquin
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- University of Navarra, Department of Preventive Medicine and Public Health, IdiSNA, 31009 Pamplona, Spain.
| | - Dolores Corella
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Preventive Medicine, University of Valencia, 46010 Valencia, Spain.
| | - Ramon Estruch
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Internal Medicine, Department of Endocrinology and Nutrition Institut d' Investigacions Biomediques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08007 Barcelona, Spain.
| | - Emilio Ros
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08007 Barcelona, Spain.
| | - Montserrat Fitó
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Cardiovascular Risk and Nutrition Research Group (CARIN), Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain.
| | - Fernando Arós
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Cardiology, University Hospital of Álava, 01009 Vitoria, Spain.
| | - Miquel Fiol
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Illes Balears Health Research Institute (IdISBa), Hospital Son Espases, 07120 Palma de Mallorca, Spain.
| | - José Lapetra
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Family, Research Unit, Distrito Sanitario Atención Primaria Sevilla, 41013 Sevilla, Spain.
| | - Cristina Ruano
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Clinical Sciences, University of Las Palmas de Gran Canaria, 35001 Las Palmas, Spain.
| | - Liming Liang
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Miguel A Martínez-González
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- University of Navarra, Department of Preventive Medicine and Public Health, IdiSNA, 31009 Pamplona, Spain.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Frank B Hu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
- Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA 02115, USA.
| | - Jordi Salas-Salvadó
- Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, 43201 Reus, Spain.
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
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Majdi A, Kamari F, Sadigh-Eteghad S, Gjedde A. Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review. Front Neurosci 2019; 12:1002. [PMID: 30697142 PMCID: PMC6341027 DOI: 10.3389/fnins.2018.01002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/12/2018] [Indexed: 01/25/2023] Open
Abstract
Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial. Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory. Methods: We searched Embase, Medline via PubMed, Scopus, and Web of Science databases for entries no later than May 2018, and restricted the search to articles about nicotine metabolites and cognitive behavior or cognitive mechanisms. Results: The initial search yielded 425 articles, of which 17 were eligible for inclusion after application of exclusion criteria. Of these, 13 were experimental, two were clinical, and two were conference papers. Conclusions: The results revealed three pharmacologically active biotransformations of nicotine in the brain, including cotinine, norcotinine, and nornicotine, among which cotinine and nornicotine both had a procognitive impact without adverse effects. The observed effect was significant only for cotinine.
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Affiliation(s)
- Alireza Majdi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzin Kamari
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeed Sadigh-Eteghad
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Albert Gjedde
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada
- Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States
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Alvarez-Ricartes N, Oliveros-Matus P, Mendoza C, Perez-Urrutia N, Echeverria F, Iarkov A, Barreto GE, Echeverria V. Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice. Mol Neurobiol 2018; 55:7949-7960. [PMID: 29488138 DOI: 10.1007/s12035-018-0916-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 01/18/2018] [Indexed: 02/07/2023]
Abstract
Failure in fear extinction is one of the more troublesome characteristics of posttraumatic stress disorder (PTSD). Cotinine facilitates fear memory extinction and reduces depressive-like behavior when administered 24 h after fear conditioning in mice. In this study, it was investigated the behavioral and molecular effects of cotinine, and other antidepressant preparations infused intranasally. Intranasal (IN) cotinine, IN krill oil, IN cotinine plus krill oil, and oral sertraline were evaluated on depressive-like behavior and fear retention and extinction after fear conditioning in C57BL/6 mice. Since calcineurin A has been involved in facilitating fear extinction in rodents, we also investigated changes of calcineurin in the hippocampus, a region key on contextual fear extinction. Short-term treatment with cotinine formulations was superior to krill oil and oral sertraline in reducing depressive-like behavior and fear consolidation and enhancing contextual fear memory extinction in mice. IN krill oil slowed the extinction of fear. IN cotinine preparations increased the levels of calcineurin A in the hippocampus of conditioned mice. In the light of the results, the future investigation of the use of IN cotinine preparations for the extinction of contextual fear memory and treatment of treatment-resistant depression (TRD) in PTSD is discussed.
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Affiliation(s)
- Nathalie Alvarez-Ricartes
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile
| | - Patricia Oliveros-Matus
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile
| | - Cristhian Mendoza
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile
| | - Nelson Perez-Urrutia
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile
| | - Florencia Echeverria
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile
| | - Alexandre Iarkov
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile.
| | - George E Barreto
- Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.,Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile
| | - Valentina Echeverria
- Facultad de Ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile. .,Bay Pines VA Healthcare System, Research and Development, Bay Pines VAHCS, 10,000 Bay Pines Blvd., Bldg. 23, Rm123, Bay Pines, FL, 33744, USA.
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34
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Rego Campello H, Gallagher T. C(5) Site-Selective Functionalization of (S)-Cotinine. J Org Chem 2018; 83:516-520. [PMID: 29207240 DOI: 10.1021/acs.joc.7b02704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
(S)-(-)-Cotinine 2 undergoes direct and site-selective iridium-catalyzed borylation to provide boronate ester 3 and bromide 4 which offer flexible entry to a range of C(5)-substituted cotinine variants.
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Affiliation(s)
- Hugo Rego Campello
- School of Chemistry, University of Bristol , Bristol BS8 1TS, United Kingdom
| | - Timothy Gallagher
- School of Chemistry, University of Bristol , Bristol BS8 1TS, United Kingdom
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35
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Zhu J, Fan F, McCarthy DM, Zhang L, Cannon EN, Spencer TJ, Biederman J, Bhide PG. A prenatal nicotine exposure mouse model of methylphenidate responsive ADHD‐associated cognitive phenotypes. Int J Dev Neurosci 2017; 58:26-34. [DOI: 10.1016/j.ijdevneu.2017.01.014] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 01/21/2017] [Accepted: 01/27/2017] [Indexed: 12/13/2022] Open
Affiliation(s)
- Jinmin Zhu
- Center for Brain Repair and The Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeFL32306United States
| | - Fangfang Fan
- Center for Brain Repair and The Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeFL32306United States
| | - Deirdre M. McCarthy
- Center for Brain Repair and The Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeFL32306United States
| | - Lin Zhang
- Center for Brain Repair and The Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeFL32306United States
| | - Elisa N. Cannon
- Center for Brain Repair and The Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeFL32306United States
| | - Thomas J. Spencer
- Pediatric Psychopharmacology, Department of PsychiatryMassachusetts General Hospital, Harvard Medical SchoolBostonMA02114United States
| | - Joseph Biederman
- Pediatric Psychopharmacology, Department of PsychiatryMassachusetts General Hospital, Harvard Medical SchoolBostonMA02114United States
| | - Pradeep G. Bhide
- Center for Brain Repair and The Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeFL32306United States
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Pardo M, Beurel E, Jope RS. Cotinine administration improves impaired cognition in the mouse model of Fragile X syndrome. Eur J Neurosci 2016; 45:490-498. [PMID: 27775852 DOI: 10.1111/ejn.13446] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 10/19/2016] [Accepted: 10/20/2016] [Indexed: 01/15/2023]
Abstract
Cotinine is the major metabolite of nicotine and has displayed some capacity for improving cognition in mouse models following chronic administration. We tested if acute cotinine treatment is capable of improving cognition in the mouse model of Fragile X syndrome, Fmr1-/- knockout mice, and if this is related to inhibition by cotinine treatment of glycogen synthase kinase-3β (GSK3β), which is abnormally active in Fmr1-/- mice. Acute cotinine treatment increased the inhibitory serine-phosphorylation of GSK3β and the activating phosphorylation of AKT, which can mediate serine-phosphorylation of GSK3β, in both wild-type and Fmr1-/- mouse hippocampus. Acute cotinine treatment improved cognitive functions of Fmr1-/- mice in coordinate and categorical spatial processing, novel object recognition, and temporal ordering. However, cotinine failed to restore impaired cognition in GSK3β knockin mice, in which a serine9-to-alanine9 mutation blocks the inhibitory serine phosphorylation of GSK3β, causing GSK3β to be hyperactive. These results indicate that acute cotinine treatment effectively repairs impairments of these four cognitive tasks in Fmr1-/- mice, and suggest that this cognition-enhancing effect of cotinine is linked to its induction of inhibitory serine-phosphorylation of GSK3. Taken together, these results show that nicotinic receptor agonists can act as cognitive enhancers in a mouse model of Fragile X syndrome and highlight the potential role of inhibiting GSK3β in mediating the beneficial effects of cotinine on memory.
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Affiliation(s)
- Marta Pardo
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.,Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Eleonore Beurel
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.,Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Richard S Jope
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.,Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA
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Fox AM, Moonschi FH, Richards CI. The nicotine metabolite, cotinine, alters the assembly and trafficking of a subset of nicotinic acetylcholine receptors. J Biol Chem 2015; 290:24403-12. [PMID: 26269589 DOI: 10.1074/jbc.m115.661827] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Indexed: 12/27/2022] Open
Abstract
Exposure to nicotine alters the trafficking and assembly of nicotinic receptors (nAChRs), leading to their up-regulation on the plasma membrane. Although the mechanism is not fully understood, nicotine-induced up-regulation is believed to contribute to nicotine addiction. The effect of cotinine, the primary metabolite of nicotine, on nAChR trafficking and assembly has not been extensively investigated. We utilize a pH-sensitive variant of GFP, super ecliptic pHluorin, to differentiate between intracellular nAChRs and those expressed on the plasma membrane to quantify changes resulting from cotinine and nicotine exposure. Similar to nicotine, exposure to cotinine increases the number of α4β2 receptors on the plasma membrane and causes a redistribution of intracellular receptors. In contrast to this, cotinine exposure down-regulates α6β2β3 receptors. We also used single molecule fluorescence studies to show that cotinine and nicotine both alter the assembly of α4β2 receptors to favor the high sensitivity (α4)2(β2)3 stoichiometry.
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Affiliation(s)
- Ashley M Fox
- From the Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506
| | - Faruk H Moonschi
- From the Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506
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38
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Barreto GE, Iarkov A, Moran VE. Beneficial effects of nicotine, cotinine and its metabolites as potential agents for Parkinson's disease. Front Aging Neurosci 2015; 6:340. [PMID: 25620929 PMCID: PMC4288130 DOI: 10.3389/fnagi.2014.00340] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Accepted: 12/04/2014] [Indexed: 01/10/2023] Open
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder, which is characterized by neuroinflammation, dopaminergic neuronal cell death and motor dysfunction, and for which there are no proven effective treatments. The negative correlation between tobacco consumption and PD suggests that tobacco-derived compounds can be beneficial against PD. Nicotine, the more studied alkaloid derived from tobacco, is considered to be responsible for the beneficial behavioral and neurological effects of tobacco use in PD. However, several metabolites of nicotine, such as cotinine, also increase in the brain after nicotine administration. The effect of nicotine and some of its derivatives on dopaminergic neurons viability, neuroinflammation, and motor and memory functions, have been investigated using cellular and rodent models of PD. Current evidence shows that nicotine, and some of its derivatives diminish oxidative stress and neuroinflammation in the brain and improve synaptic plasticity and neuronal survival of dopaminergic neurons. In vivo these effects resulted in improvements in mood, motor skills and memory in subjects suffering from PD pathology. In this review, we discuss the potential benefits of nicotine and its derivatives for treating PD.
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Affiliation(s)
- George E Barreto
- Department of Nutrition and Biochemistry, Pontificia Universidad Javeriana Bogotá, D. C., Colombia
| | - Alexander Iarkov
- Center of Research in Biomedical Sciences, Universidad Autónoma de Chile Santiago, Chile ; Research & Development Service, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Valentina Echeverria Moran
- Center of Research in Biomedical Sciences, Universidad Autónoma de Chile Santiago, Chile ; Research & Development Service, Bay Pines VA Healthcare System Bay Pines, FL, USA ; Research Service, James A Haley Veterans' Hospital Tampa, FL, USA ; Department of Molecular Medicine, Morsani College of Medicine, University of South Tampa, FL, USA
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Kim H, Yoon S, Chung J. In vitro and in vivo application of anti-cotinine antibody and cotinine-conjugated compounds. BMB Rep 2014; 47:130-4. [PMID: 24499668 PMCID: PMC4163880 DOI: 10.5483/bmbrep.2014.47.3.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Revised: 01/09/2014] [Accepted: 01/20/2014] [Indexed: 12/04/2022] Open
Abstract
The combination of a high-affinity antibody to a hapten, and hapten-conjugated compounds, can provide an alternative to the direct chemical cross-linking of the antibody and compounds. An optimal hapten for in vitro use is one that is absent in biological systems. For in vivo applications, additional characteristics such as pharmacological safety and physiological inertness would be beneficial. Additionally, methods for cross-linking the hapten to various chemical compounds should be available. Cotinine, a major metabolite of nicotine, is considered advantageous in these aspects. A high-affinity anti-cotinine recombinant antibody has recently become available, and can be converted into various formats, including a bispecific antibody. The bispecific anti-cotinine antibody was successfully applied to immunoblot, enzyme immunoassay, immunoaffinity purification, and pre-targeted in vivo radioimmunoimaging. The anti-cotinine IgG molecule could be complexed with aptamers to form a novel affinity unit, and extended the in vivo half-life of aptamers, opening up the possibility of applying the same strategy to therapeutic peptides and chemical compounds. [BMB Reports 2014; 47(3): 130-134]
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Affiliation(s)
- Hyori Kim
- Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799; Cancer Research Institute, Seoul National University, Seoul 110-799, Korea
| | - Soomin Yoon
- Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea
| | - Junho Chung
- Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799; Cancer Research Institute, Seoul National University, Seoul 110-799, Korea
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40
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Kim KM, Suh JW, Yang SH, Kim BR, Park TS, Shim SM. Smilax China root extract detoxifies nicotine by reducing reactive oxygen species and inducing CYP2A6. J Food Sci 2014; 79:H2132-9. [PMID: 25220663 DOI: 10.1111/1750-3841.12595] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Accepted: 08/03/2014] [Indexed: 01/31/2023]
Abstract
UNLABELLED Resveratrol has a beneficial effect of lowering reactive oxygen species (ROS) and reduces cellular oxidative stress. We hypothesized that ethanol extract of Smilax china root (EESC) rich in resveratrol (RES) and oxyresveratrol (OXY) could reduce ROS caused by nicotine and promoting nicotine turnover by induction of CYP2A6. The amount of cotinine converted from nicotine was quantified by the direct barbiturate assay method. Expression of CYP2A6 was unregulated by RES, OXY, or EESC, respectively. Pretreatment of RES (50, 100, and 250 μM), OXY (50, 100, and 250 μM), and RES+OXY (50 and 100 μM) inhibited cytotoxicity and ROS production caused by nicotine in a dose-dependent manner. EESC pretreatment (1.8 mg/mL) increased cell viability by 1.5-fold higher than the control (nicotine only), and lowered cellular ROS levels. A significant amount of the conversion of nicotine to cotinine was observed in EESC pretreatment by CYP2A6 induction in HepG2 cells. These results suggested that hepatic induction of CYP2A6 and ROS reduction by EESC activate nicotine metabolism and reduce cellular oxidative stress. PRACTICAL APPLICATION Nicotine exposure due to smoking is very concerning because it is the major factor for lung diseases and cardiovascular disorders. It is necessary to examine natural ingredients that can detoxify from nicotine to cotinine as well as neutralize free radicals induced from nicotine. Results from the current study suggest potential applications of Smilax china root for detoxification of nicotine in the food industry.
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Affiliation(s)
- Kyeong-Mu Kim
- Dept. of Food Science and Technology, Sejong Univ, 98 Gunja-dong, Seoul, 143-747, Republic of Korea
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Nicotine detoxification of rutin, quercitrin, and chlorogenic acid isolated from Houttuynia cordata by reducing reactive oxygen species and inducing conversion from nicotine to cotinine. ACTA ACUST UNITED AC 2014. [DOI: 10.1007/s13765-014-4182-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Patel S, Grizzell JA, Holmes R, Zeitlin R, Solomon R, Sutton TL, Rohani A, Charry LC, Iarkov A, Mori T, Echeverria Moran V. Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice. Front Aging Neurosci 2014; 6:162. [PMID: 25100990 PMCID: PMC4107855 DOI: 10.3389/fnagi.2014.00162] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 06/24/2014] [Indexed: 12/29/2022] Open
Abstract
Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.
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Affiliation(s)
- Sagar Patel
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - J Alex Grizzell
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA ; Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida Tampa, FL, USA
| | - Rosalee Holmes
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Ross Zeitlin
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Rosalynn Solomon
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Thomas L Sutton
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Adeeb Rohani
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Laura C Charry
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA
| | - Alexandre Iarkov
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA ; Center of Research in Biomedical Sciences, Universidad Autónoma de Chile Santiago, Chile
| | - Takashi Mori
- Departments of Biomedical Sciences and Pathology, Saitama Medical Center and Saitama Medical University Kawagoe, Saitama, Japan
| | - Valentina Echeverria Moran
- Research and Development Service, Department of Veterans Affairs, Bay Pines VA Healthcare System Bay Pines, FL, USA ; Center of Research in Biomedical Sciences, Universidad Autónoma de Chile Santiago, Chile ; Research Service, Department of Veterans Affairs, Tampa VA Healthcare System Tampa, FL, USA ; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida Tampa, FL, USA
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Grizzell JA, Echeverria V. New Insights into the Mechanisms of Action of Cotinine and its Distinctive Effects from Nicotine. Neurochem Res 2014; 40:2032-46. [PMID: 24970109 DOI: 10.1007/s11064-014-1359-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 06/10/2014] [Indexed: 12/20/2022]
Abstract
Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use. Popular dogma holds that this component is nicotine. However, increasing evidence support theories that cotinine, the main metabolite of nicotine, may underlie at least some of nicotine's actions in the nervous system, apart from its adverse cardiovascular and habit forming effects. Though similarities exist, disparate and even antagonizing actions between cotinine and nicotine have been described both in terms of behavior and physiology, underscoring the need to further characterize this potentially therapeutic compound. Cotinine has been shown to be psychoactive in humans and animals, facilitating memory, cognition, executive function, and emotional responding. Furthermore, recent research shows that cotinine acts as an antidepressant and reduces cognitive-impairment associated with disease and stress-induced dysfunction. Despite these promising findings, continued focus on this potentially safe alternative to tobacco and nicotine use is lacking. Here, we review the effects of cotinine, including comparisons with nicotine, and discuss potential mechanisms of cotinine-specific actions in the central nervous system which are, to date, still being elucidated.
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Affiliation(s)
- J Alex Grizzell
- Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, 33611, USA.,Department of Research and Development, Bay Pines VA Healthcare System, 10,000 Bay Pines Blvd., Bldg. 23, Rm. 123, Bay Pines, FL, 33744, USA
| | - Valentina Echeverria
- Department of Research and Development, Bay Pines VA Healthcare System, 10,000 Bay Pines Blvd., Bldg. 23, Rm. 123, Bay Pines, FL, 33744, USA. .,Universidad Autónoma de Chile, Carlos Antúnez 1920, Providencia, Santiago, Chile. .,Department of Molecular Medicine, University of South Florida, Tampa, FL, 33647, USA.
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Yoon S, Kim YH, Kang SH, Kim SK, Lee HK, Kim H, Chung J, Kim IH. Bispecific Her2 × cotinine antibody in combination with cotinine-(histidine)2-iodine for the pre-targeting of Her2-positive breast cancer xenografts. J Cancer Res Clin Oncol 2014; 140:227-33. [PMID: 24292501 DOI: 10.1007/s00432-013-1548-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Accepted: 11/11/2013] [Indexed: 10/26/2022]
Abstract
PURPOSE Cotinine has optimal characteristics as a hapten for pre-targeted radioimmunotherapy (PRIT). This study was performed to evaluate the applicability of cotinine/anti-cotinine antibody to PRIT. METHODS We developed and prepared a tandem, single-chain, variable fragment Fc fusion protein [tandem single-chain variable fragment (scFv) Fc fusion protein] that is reactive to both human epidermal growth factor receptor 2 (Her2) and cotinine. Its simultaneous reactivity to Her2 and cotinine was tested in an enzyme-linked immunosorbent assay (ELISA) and two radioimmunoassays (RIA) employing Her2-coated RIA tubes and a Her2-overexpressing cell line. For in vivo imaging, mice bearing Her2-positive tumors were injected with a mixture of tandem scFv Fc fusion and (125)I-cotinine-conjugated histidine dipeptide ((125)I-cotinine peptide). After a delay, (125)I-cotinine peptide was injected again. RESULTS ELISA and RIA results showed that tandem scFv Fc fusion protein successfully bound to both Her2 and cotinine. In single-photon emission computed tomography (SPECT), the complex of tandem scFv Fc fusion protein and (125)I-cotinine peptide was localized to Her2-positive tumor xenografts in mice 4 h after the first injection. Enhanced radioactivity at the site of the Her2-positive tumor lesion was monitored 1 h after the second injection. CONCLUSIONS With these findings, we conclude that the tandem scFv Fc fusion protein and cotinine hapten system have the potential to be applied in PRIT.
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Affiliation(s)
- Soomin Yoon
- Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, 110-799, Republic of Korea
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