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Drug and Alcohol Dependence Oct 2022Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting... (Review)
Review
BACKGROUND
Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation.
METHODS
A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized.
RESULTS
People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs.
CONCLUSION
Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.
Topics: Bupropion; Genetic Variation; Humans; Nicotine; Polymorphism, Single Nucleotide; Receptors, Nicotinic; Smoking Cessation; Tobacco Products; Tobacco Use Cessation Devices
PubMed: 35981468
DOI: 10.1016/j.drugalcdep.2022.109596 -
Acta Psychiatrica Scandinavica Apr 2022The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT.
METHODS
Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random-effects models were used. PROSPERO registration number was CRD42021212773.
RESULTS
Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention-types. Quantitative synthesis (meta-analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention-types. Low-quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low-quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low-quality), herbal preparations with anti-inflammatory properties (very low to low-quality) and opioid receptor agonists (low-quality).
CONCLUSION
Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT.
Topics: Cognition; Electroconvulsive Therapy; Humans; Ketamine; Memantine; Triiodothyronine
PubMed: 35075641
DOI: 10.1111/acps.13397 -
Chemical Biology & Drug Design Dec 2023Alzheimer's disease (AD) is a chronic age-related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability... (Review)
Review
Alzheimer's disease (AD) is a chronic age-related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability of an individual. The exact pathophysiology of AD is not fully understood. However low level of the neurotransmitter named acetylcholine (ACh), aggregation of Aβ peptide into toxic Aβ plaque, hyperphosphorylation of tau, bio-metal imbalance, and oxidative stress are the main hallmarks of this disease. Due to the complex pathophysiology of AD, no specific treatment is available in the market, and treatment is only limited to the symptomatic relief. So, there is an urgent need for the development of new drug candidate, which can have disease-modifying effect and improve learning and memory in AD patient. Therefore, berberine-based multifunction compounds with potential cholinesterase inhibitory properties were reviewed in this article. Structure-activity relationship (SAR) and biological activity provide highlights on the new derivatives used for the management of AD.
Topics: Humans; Amyloid beta-Peptides; Acetylcholinesterase; Berberine; Alzheimer Disease; Oxidative Stress; Cholinesterase Inhibitors
PubMed: 37665093
DOI: 10.1111/cbdd.14337 -
Frontiers in Pharmacology 2023Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the...
Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the migrating myoelectric complex component of GI motility. Changes in MLN availability are associated with GI diseases such as gastroesophageal reflux disease and functional dyspepsia. Furthermore, herbal medicines have been used for several years to treat various GI disorders. We systematically reviewed clinical and animal studies on how herbal medicine affects the modulation of MLN and subsequently brings the therapeutic effects mainly focused on GI function. We searched the PubMed, Embase, Cochrane, and Web of Science databases to collect all articles published until 30 July 2023, that reported the measurement of plasma MLN levels in human randomized controlled trials and herbal medicine studies. The collected characteristics of the articles included the name and ingredients of the herbal medicine, physiological and symptomatic changes after administering the herbal medicine, changes in plasma MLN levels, key findings, and mechanisms of action. The frequency patterns (FPs) of botanical drug use and their correlations were investigated using an FP growth algorithm. Nine clinical studies with 1,308 participants and 20 animal studies were included in the final analyses. Herbal medicines in clinical studies have shown therapeutic effects in association with increased levels of MLN, including GI motility regulation and symptom improvement. Herbal medicines have also shown anti-stress, anti-tumor, and anti-inflammatory effects . Various biochemical markers may correlate with MLN levels. Markers may have a positive correlation with plasma MLN levels included ghrelin, acetylcholine, and secretin, whereas a negative correlation included triglycerides and prostaglandin E. Markers, such as gastrin and somatostatin, did not show any correlation with plasma MLN levels. Based on the FP growth algorithm, and were the most frequently used species. Herbal medicine may have therapeutic effects mainly on GI symptoms with involvement of MLN regulation and may be considered as an alternative option for the treatment of GI diseases. Further studies with more solid evidence are needed to confirm the efficacy and mechanisms of action of herbal medicines. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=443244, identifier CRD42023443244.
PubMed: 38161695
DOI: 10.3389/fphar.2023.1286333 -
Medicine Apr 2021To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the efficacy of double-filtration plasmapheresis (DFPP) treatment of myasthenia gravis (MG) through a systematic review and meta-analysis.
METHODS
PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) on DFPP for MG from database establishment to June 2019. Two researchers independently screened the articles, extracted the data, and cross checked the results. RevMan 5.3 was used for statistical analyses.
RESULTS
Seven RCTs and 2 CCTs were found comprising 329 patients. The results showed that clinical MG remission rate after DFPP treatment was significantly higher (OR = 4.33; 95% confidence interval [CI], 1.97-9.53; P < .001) and the serum levels of antititin antibody was significantly decreased (standardized mean difference [SMD] = 9.30; 95% CI, 7.51-11.08; P < .001). In addition, the quantitative MG (QMG) score, hospital stay and time to remission of MG symptoms, and acetylcholine receptor antibody (AchRAb) decreased in the DFPP treatment group; however, these outcomes had high heterogeneity among the studies. Only one study has reported on the adverse effects, including hypotension and hematoma.
CONCLUSION
This meta-analysis suggests that DFPP can be recommended for the short-term mitigation of MG. Because our review was limited by the quantity and quality of the included studies, the above conclusions should be verified by additional high-quality studies.
Topics: Adult; Autoantibodies; Female; Humans; Length of Stay; Male; Middle Aged; Myasthenia Gravis; Non-Randomized Controlled Trials as Topic; Plasmapheresis; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 33907116
DOI: 10.1097/MD.0000000000025622 -
Cureus Jan 2024Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that... (Review)
Review
Parkinson's disease (PD) is a terminal, debilitating neurodegenerative disorder typically affecting individuals over 60. It is associated with various conditions that drastically affect the patient's quality of life (QoL). Although there is no cure for PD, its symptoms can be significantly improved and even resolved through different treatments. Mainstay treatments for PD include levodopa combined with carbidopa, dopamine agonists, and even deep brain stimulation (DBS) of the subthalamic nucleus. New treatment methods have emerged, such as botulinum toxin (BoNT), which further improve symptoms and, thus, the QoL of patients with PD. Botulinum toxin is a potent neurotoxin produced by that typically causes descending paralysis by suppressing acetylcholine secretion. Serotypes used to treat various disorders include serotype A (BoNT-A) and serotype B (BoNT-B). This paper aims to evaluate the outcomes of BoNT injection on different symptoms associated with PD. An extensive review using PubMed, ScienceDirect, and ProQuest articles concerning 'botulinum toxin and Parkinson's disease' was done per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in 23,803 articles. After applying strict inclusion and exclusion criteria, the total number of articles was finally 41. The results showed that movement disorders were a common occurrence in PD, consisting of tremors, dystonia, and freezing of gait (FOG), with tremors being the most common symptom. Tremors and dystonia were significantly improved following BoNT-A, correlating with significant improvements in various scales subjectively and objectively evaluating the symptoms and QoL. In contrast, FOG was not significantly improved by either BoNT-A or BoNT-B. Pain is associated with movement disorders such as PD and was the primary indication for the administration of BoNT; studies found pain and QoL were significantly improved following BoNT injection. Quality of life can also be affected by sialorrhea and overactive bladder, which often occur as the disease progresses. Injections of BoNT-A and BoNT-B were shown to significantly improve saliva production, flow rate, drooling frequency, voiding frequency, and urinary urge incontinence. Across all studies analyzed, it is evident that BoNT may have a significant effect on improving the QoL of patients suffering from PD. While research continues to find a cure or stop the progression of PD, it remains critical to continue focusing on improving patients' QoL. Future research should evaluate whether BoNT can be used to successfully treat other symptoms of PD, such as epiphora or constipation.
PubMed: 38435899
DOI: 10.7759/cureus.53309 -
European Journal of Neurology Jan 2023Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in... (Review)
Review
BACKGROUND AND PURPOSE
Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in MG is unclear. We sought to evaluate this landscape through systematically assessing the evidence, testing the impact of predefined variables on any relationship, and augmenting with expert opinion.
METHODS
In October 2020, a forum of leading clinicians and researchers in neurology from across Europe (Expert Forum for Rare Autoantibodies in Neurology in Myasthenia Gravis) participated in a series of virtual meetings that took place alongside the conduct of a systematic literature review (SLR).
RESULTS
Forty-two studies were identified meeting inclusion criteria. Of these, 10 reported some correlation between a patient's autoantibody level and disease severity. Generally, decreased autoantibody levels (acetylcholine receptor, muscle-specific kinase, and titin) were positively and significantly correlated with improvements in disease severity (Quantitative Myasthenia Gravis score, Myasthenia Gravis Composite score, Myasthenia Gravis Activities of Daily Living score, Myasthenia Gravis Foundation of America classification). Given the limited evidence, testing the impact of predefined variables was not feasible.
CONCLUSIONS
This first SLR to assess whether a correlation exists between autoantibody levels and disease activity in patients with MG has indicated a potential positive correlation, which could have clinical implications in guiding treatment decisions. However, in light of the limited and variable evidence, we cannot currently recommend routine clinical use of autoantibody level testing in this context. For now, patient's characteristics, clinical disease course, and laboratory data (e.g., autoantibody status, thymus histology) should inform management, alongside patient-reported outcomes. We highlight the need for future studies to reach more definitive conclusions on this relationship.
Topics: Humans; Activities of Daily Living; Myasthenia Gravis; Autoantibodies; Immunoglobulin G; Biomarkers
PubMed: 36094738
DOI: 10.1111/ene.15565 -
Neurochemical Research Dec 2023Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD).... (Review)
Review
Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.
Topics: Animals; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Neuroprotective Agents; Xanthones
PubMed: 37578655
DOI: 10.1007/s11064-023-04005-8 -
Progress in Neuro-psychopharmacology &... Dec 2020Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD...
BACKGROUND
Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD mechanisms are not fully understood, and no pharmacological solution exists for its cessation therapy.
METHODS
We present a systematic review on BQD mechanisms and examine potential cessation therapeutic drugs. We conducted a systematic literature search in PubMed and Web of Science databases and identified the latest 10 years' relevant articles for reviews.
RESULTS
Functional magnetic resonance imaging results demonstrate that neurological mechanisms link the brain reward, cognitive, and impulsive systems in BQ or BQD users. The use of the areca nut increases both brain serotonin and noradrenaline levels, whereas arecoline, a potentially addictive areca nut component, has monoamine oxidase-A (MAO-A) inhibitor-like properties. MAO-A inhibitors prevent neurotransmitter breakdown and increase dopamine and serotonin concentrations in the brain. A reduction of daily BQ use was observed among patients with depression after antidepressant therapy, including MAO-A inhibitor and selective serotonin reuptake inhibitor (SSRI). Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. However, relatively negligible amounts of nicotine are detected in the areca nut.
CONCLUSION
In conclusion, the current evidence provides a better understanding of the neurological and pharmacological mechanisms behind BQD. Arecoline, an MAO-A inhibitor, may account for BQD. Future translational studies are needed to verify the efficacy of potential BQD cessation drugs. MAO-A inhibitor and SSRI would thus be potentially promising targets for clinical trials.
Topics: Animals; Areca; Arecoline; Behavior, Addictive; Brain Chemistry; Humans; Magnetic Resonance Imaging; Monoamine Oxidase Inhibitors; Substance-Related Disorders
PubMed: 32454163
DOI: 10.1016/j.pnpbp.2020.109982 -
Toxins Apr 2024Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of... (Review)
Review
Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.
Topics: Humans; Mental Disorders; Botulinum Toxins, Type A; Clinical Trials as Topic; Treatment Outcome
PubMed: 38668616
DOI: 10.3390/toxins16040191