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Environmental Research Dec 2023Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are... (Meta-Analysis)
Meta-Analysis
Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: A systematic review and meta-analysis.
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps.
OBJECTIVE
We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies.
METHODS
A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7, 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis.
RESULTS
We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all β [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (p = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (p = 0.02) and paraoxonase-1 (p = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase.
CONCLUSIONS
Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity.
Topics: Humans; Antioxidants; Biomarkers; Environmental Pollutants; Fluorocarbons; Halogenated Diphenyl Ethers; Hydrocarbons, Chlorinated; Malondialdehyde; Oxidative Stress; Pesticides; Polychlorinated Biphenyls
PubMed: 37813138
DOI: 10.1016/j.envres.2023.117308 -
Journal of Neurology May 2015Myasthenia gravis is an autoimmune disorder of the neuromuscular junction caused by circulating antibodies specific for the post-synaptic acetylcholine receptor or, in a... (Meta-Analysis)
Meta-Analysis Review
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction caused by circulating antibodies specific for the post-synaptic acetylcholine receptor or, in a minority of cases, for the muscle-specific tyrosine-kinase and the low-density lipoprotein receptor-related protein 4. A wide range of symptomatic and immunosuppressive treatments is currently available for MG patients with variable outcome. However, most immunosuppressive treatments are characterized by delayed onset of action and in some cases are not sufficient to induce stable remission of the disease. Rituximab (RTX) is a chimaeric monoclonal antibody specific for the CD20 B-cell surface antigen. Recent studies have provided evidence that RTX may be an effective treatment for patients with myasthenia gravis (MG) who are refractory to standardized immunosuppressive therapy. We performed a systematic review and a meta-analysis of the efficacy and safety of RTX in myasthenia gravis considering the potential predictive factors related to patients' response to RTX in this disease.
Topics: Humans; Immunologic Factors; Myasthenia Gravis; PubMed; Rituximab; Treatment Outcome
PubMed: 25308632
DOI: 10.1007/s00415-014-7532-3 -
European Journal of Neurology Jan 2022Sialorrhea often happens in patients with neurologic disorders, and botulinum toxin (BoNT), which inhibits acetylcholine activation, may be an effective treatment for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Sialorrhea often happens in patients with neurologic disorders, and botulinum toxin (BoNT), which inhibits acetylcholine activation, may be an effective treatment for drooling. This systematic review and meta-analysis of randomized control trials aims to evaluate the efficacy and safety of BoNT in adults and children with sialorrhea due to neurological disorders.
METHODS
The PubMed, Embase, and Cochrane databases were searched for relevant studies published before August 2021. The pooled estimate of outcomes was calculated using a random effect model.
RESULTS
The review included 17 studies involving 981 patients. Compared with placebo, both BoNT type A (BoNT-A) and BoNT type B (BoNT-B) alleviated drooling frequency and severity (mean difference, 95% CI; BoNT-A: -1.20, -1.89 to -0.51; BoNT-B: -1.62, -2.07 to -1.17), reduced saliva weight (BoNT-A: -1.70, -2.30 to -1.10; BoNT-B: -1.12, -1.97 to -0.27), and improved global impression of change (BoNT-A: -1.30, -1.73 to -0.86; BoNT-B: -1.58, -1.95 to -1.21) in adults 4 weeks postinjection. BoNT-B remained effective at 12 weeks. In children, BoNT-A and BoNT-B alleviated sialorrhea symptoms (BoNT-A: -1.63, -2.42 to -0.85; BoNT-B: -5.20, -6.03 to -4.37) and BoNT-A reduced saliva weight (-0.77, -1.54 to 0.00) at 4 weeks postinjection. After 12 weeks, BoNT-B remained efficacious. Most adverse effects (AEs) were mild to moderate and self-limited.
CONCLUSIONS
There is moderate certainty of evidence (COE) that either BoNT-A or BoNT-B could relieve sialorrhea after 4 and 12 weeks of follow-up without significantly more severe AEs in adults. However, the COE is very low to low in children.
Topics: Botulinum Toxins, Type A; Child; Humans; Neuromuscular Agents; Sialorrhea; Treatment Outcome
PubMed: 34449931
DOI: 10.1111/ene.15083 -
Frontiers in Pharmacology 2020Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. C. A. Mey (PG) is an important herbal drug which has been used for...
BACKGROUND
Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. C. A. Mey (PG) is an important herbal drug which has been used for benefiting Qi for thousand years. C. A. Mey and its compounds (PGC) possess various pharmacological activities, including anti-fatigue. Here, we conducted a systematic review of both randomized clinical trials (RCTs) and preclinical animal studies to investigate the efficacy and safety of PGC for fatigue.
METHODS
Electronic searches were performed in 7 databases from the time of each database's inception to August 2019. The methodological quality of RCTs was assessed using 7-item checklist recommended by Cochrane Collaboration or by the CAMARADES 10-item quality checklist. All the data were analyzed using Rev-Man 5.3 and Stata SE software.
RESULTS
Eight eligible RCTs and 30 animal studies were identified. The risk of bias scores in RCTs ranged from 4/7 to 7/7, and of animal studies varied from 4/10 to 7/10. Meta-analyses showed that PGC was superior to placebo according to their respective fatigue scales, heart rate recovery, and clinical effect (P < 0.05). There were a similar number of adverse effects between PGC and placebo group (P > 0.05). Meta-analyses showed that PGC can significantly decrease level of blood lactate, blood urea nitrogen, creatine kinase, malondialdehyde, and lactic dehydrogenase in serum, level of malondialdehyde in liver and level of gamma-aminobutyric acid, 5-hydroxytryptamine in brain tissue, and increase swimming time, level of glutathione peroxidase, glucose, superoxide dismutase in serum, level of glycogen and activity of superoxide dismutase, glutathione peroxidase, and catalase in skeletal muscle, level of hepatic glycogen in liver and level of dopamine, acetylcholine in brain tissue, compared with control (P < 0.05). Meta-analyses showed no significant difference in animal body weight between PGC and control (P > 0.05).
CONCLUSION
The present findings supported, to a certain degree, that PGC can be recommended for routine use in fatigue. The possible mechanism of PGC resists fatigue, mainly through antioxidant stress, regulating carbohydrate metabolism, delaying the accumulation of metabolites, promoting mitochondrial function, neuroprotection, antiapoptosis, and regulating neurotransmitter disorder in central nervous system.
PubMed: 32765262
DOI: 10.3389/fphar.2020.01031 -
Urology Feb 2017To evaluate the efficacy and safety of OnabotulinumtoxinA treatment in the management of overactive bladder syndrome. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of OnabotulinumtoxinA treatment in the management of overactive bladder syndrome.
MATERIALS AND METHODS
A systematic review of the literature and meta-analysis was performed including randomized controlled clinical trials that compared the use of OnabotulinumtoxinA with the use of placebo, antimuscarinic medication, or different doses of OnabotulinumtoxinA. Eleven studies met inclusion criteria and did not have any exclusion criteria. Primary outcome is improvement of urge incontinence, urinary frequency, and urinary urgency. Secondary outcomes are adverse events (urinary tract infection, urinary retention) and quality of life. Outcomes were evaluated after a 12-week follow-up period. Independent evaluation of the study's quality using the CONSORT (Consolidated Standards of Reporting Trials) tool was made. Analysis was performed in Review Manager 5.2.
RESULTS
Compared with placebo, OnabotulinumtoxinA significantly decreased the number of episodes of urge incontinence. Urinary tract infection was more frequent in patients treated with OnabotulinumtoxinA than in patients treated with placebo. Frequency of urinary retention was not significantly different between patients treated with 100 IU OnabotulinumtoxinA dose and those treated with higher doses. Quality of life was assessed with different instruments in 3 of the studies; this implied a limitation because it was not possible to compare these data.
CONCLUSION
Intravesical injections of OnabotulinumtoxinA compared with placebo showed a statistically significant improvement in the treatment of overactive bladder. Adverse events were more frequent among patients treated with OnabotulinumtoxinA. This meta-analysis takes into account only randomized placebo controlled trials.
Topics: Acetylcholine Release Inhibitors; Administration, Intravesical; Botulinum Toxins, Type A; Humans; Risk Assessment; Urinary Bladder, Overactive
PubMed: 27789302
DOI: 10.1016/j.urology.2016.10.026 -
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 -
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 -
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 -
Ageing Research Reviews Jul 2014To date, single drug and nutrient-based interventions have failed to show a clinically relevant effect on Alzheimer's disease (AD). Multidomain interventions may... (Review)
Review
To date, single drug and nutrient-based interventions have failed to show a clinically relevant effect on Alzheimer's disease (AD). Multidomain interventions may alleviate symptoms and alter the disease course in a synergistic manner. This systematic review examines the effect of adding nutritional supplementation to cholinesterase inhibitors. A systematic PubMed and Cochrane search resulted in nine high quality studies. The studies had low to moderate risk of bias and focused on oxidative stress, homocysteine levels, membrane fluidity, inflammation and acetylcholine levels. Only the use of vitamin E supplements could reduce the rate of functional decline when combined with cholinesterase inhibitors in one study, whereas cognition was not affected in both this and other studies. None of the other nutritional supplements showed convincing evidence of a beneficial effect when combined with cholinesterase inhibitors. This shows that cognitive and functional improvement is difficult to achieve in patients with AD, despite epidemiological data and evidence of biological effects of nutritional supplements. Addressing one disease pathway in addition to cholinesterase inhibitor therapy is probably insufficient to alter the course of the disease. Personalized, multifactorial interventions may be more successful in improving cognition and daily functioning.
Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Cognition; Dietary Supplements; Drug Therapy, Combination; Female; Humans; Male; Nutritional Status; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24982004
DOI: 10.1016/j.arr.2014.06.002