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Phytomedicine : International Journal... Jan 2021Epilepsy affects more than 65 million people worldwide. Treatment for epileptic seizures is ineffective and has many adverse effects. For this reason, the search for new...
BACKGROUND
Epilepsy affects more than 65 million people worldwide. Treatment for epileptic seizures is ineffective and has many adverse effects. For this reason, the search for new therapeutic options capable of filling these limitations is necessary.
HYPOTHESIS/PURPOSE
In this sense, natural products, such as monoterpenes, have been indicated as a new option to control neurological disorders such as epilepsy.
STUDY DESIGN
Therefore, the objective of this study was to review the monoterpenes that have anticonvulsive activity in animal models.
METHODS
The searches were performed in the PubMed, Web of Science and Scopus databases in September, 2020 and compiled studies using monoterpenes as an alternative to seizure. Two independent reviewers performed the study selection, data extraction and methodological quality assessment using the Syrcle tool.
RESULTS
51 articles that described the anticonvulsant activity of 35 monoterpenes were selected with action on the main pharmacological target, including GABAA receptors, glutamate, calcium channels, sodium and potassium. In addition, these compounds are capable of reducing neuronal inflammation and oxidative stress caused by seizure.
CONCLUSION
These compounds stand out as a promising alternative for acting through different pharmacological mechanisms, which may not only reduce seizure, but also promote neuroprotective effect by reducing toxicity in brain regions. However, further studies are needed to determine the mechanism of action and safety assessment of these compounds.
Topics: Animals; Anticonvulsants; Brain; Humans; Monoterpenes; Neuroprotective Agents; Seizures
PubMed: 33310306
DOI: 10.1016/j.phymed.2020.153422 -
PloS One 2014Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.
METHODS
A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies.
RESULTS
KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.
CONCLUSION
KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.
Topics: Adult; Aged; Asian People; Case-Control Studies; DNA Copy Number Variations; Diabetes Mellitus, Type 2; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; India; Middle Aged; Polymorphism, Single Nucleotide; Potassium Channels, Inwardly Rectifying; White People
PubMed: 25247988
DOI: 10.1371/journal.pone.0107021 -
PloS One 2017Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS.
METHODS
Serum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
We did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results.
CONCLUSION
We found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.
Topics: Adult; Aged; Aged, 80 and over; Antibodies; Autoantigens; Cell Line; Female; Glycosylation; HEK293 Cells; Humans; Male; Middle Aged; Multiple Sclerosis; Potassium Channels, Inwardly Rectifying; Prospective Studies; Young Adult
PubMed: 28414733
DOI: 10.1371/journal.pone.0175538 -
Journal of Clinical Pharmacology May 2017A systematic review was performed to categorize the hERG (human ether-a-go-go-related gene) liability of antihistamines, antipsychotics, and anti-infectives and to... (Review)
Review
A systematic review was performed to categorize the hERG (human ether-a-go-go-related gene) liability of antihistamines, antipsychotics, and anti-infectives and to compare it with current clinical risk of torsade de pointes (TdP). Eligible studies were hERG assays reporting half-minimal inhibitory concentrations (IC50). A "hERG safety margin" was calculated from the IC50 divided by the peak human plasma concentration (free C ). A margin below 30 defined hERG liability. Each drug was assigned an "uncertainty score" based on volume, consistency, precision, and internal and external validity of evidence. The hERG liability was compared to existing knowledge on TdP risk (www.credibledrugs.org). Of 1828 studies, 82 were eligible, allowing calculation of safety margins for 61 drugs. Thirty-one drugs (51%) had evidence of hERG liability including 6 with no previous mention of TdP risk (eg, desloratadine, lopinavir). Conversely, 16 drugs (26%) had no evidence of hERG liability including 6 with known, or at least conditional or possible, TdP risk (eg, chlorpromazine, sulpiride). The main sources of uncertainty were the validity of the experimental conditions used (antihistamines and antipsychotics) and nonuse of reference compounds (anti-infectives). In summary, hERG liability was categorized for 3 widely used drug classes, incorporating a qualitative assessment of the strength of available evidence. Some concordance with TdP risk was observed, although several drugs had hERG liability without evidence of clinical risk and vice versa. This may be due to gaps in clinical evidence, limitations of hERG/C data, or other patient/drug-specific factors that contribute to real-life TdP risk.
Topics: Animals; Anti-Infective Agents; Antipsychotic Agents; Ether-A-Go-Go Potassium Channels; Histamine Antagonists; Humans; Inhibitory Concentration 50; Risk Factors; Torsades de Pointes
PubMed: 28019033
DOI: 10.1002/jcph.838 -
Frontiers in Genetics 2021Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of...
Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of people with diabetes experience at least one ADR. However, there is notable interindividual heterogeneity resulting in patient harm and unnecessary medical costs. Genomics is at the forefront of research to understand interindividual variability, and there are many genotype-drug response associations in diabetes with inconsistent findings. Here, we conducted a systematic review to comprehensively examine and synthesize the effect of genetic polymorphisms on the incidence of ADRs of oral glucose-lowering drugs in people with type 2 diabetes. A literature search was made to identify articles that included specific results of research on genetic polymorphism and adverse effects associated with oral glucose-lowering drugs. The electronic search was carried out on 3rd October 2020, through Cochrane Library, PubMed, and Web of Science using keywords and MeSH terms. Eighteen articles consisting of 10, 383 subjects were included in this review. Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by ) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by ) or serotonin transporter (SERT, encoded by ) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. These effects were shown to exacerbate by concomitant treatment with gut transporter inhibiting drugs. The CYP2C9 alleles, (rs1799853C>T) and (rs1057910A>C) that are predictive of low enzyme activity were more common in subjects who experienced hypoglycemia after treatment with sulfonylureas. However, there was no significant association between sulfonylurea-related hypoglycemia and genetic variants in the ATP-binding cassette transporter sub-family C member 8 ()Potassium Inwardly Rectifying Channel Subfamily J Member 11 (. Compared to the wild type, the low enzyme activity C allele at CYP2C8 (rs1057910A>C) was associated with less weight gain whereas the C allele at rs6123045 in the gene was significantly associated with edema from rosiglitazone treatment. In spite of limited studies investigating genetics and ADR in diabetes, some convincing results are emerging. Genetic variants in genes encoding drug transporters and metabolizing enzymes are implicated in metformin-related GI adverse effects, and sulfonylurea-induced hypoglycemia, respectively. Further studies to investigate newer antidiabetic drugs such as DPP-4i, GLP-1RA, and SGLT2i are warranted. In addition, pharmacogenetic studies that account for race and ethnic differences are required.
PubMed: 34194474
DOI: 10.3389/fgene.2021.675053 -
Gender Medicine Jun 2008Women are at an increased risk of drug-induced long QT syndrome (LQTS). This major cardiac adverse effect may lead to malignant polymorphic ventricular tachycardias,... (Review)
Review
BACKGROUND
Women are at an increased risk of drug-induced long QT syndrome (LQTS). This major cardiac adverse effect may lead to malignant polymorphic ventricular tachycardias, termed torsades de pointes, which may degenerate into ventricular fibrillation and cause sudden death.
OBJECTIVE
This article reviews current evidence and remaining gaps in knowledge about drug-induced LQTS in women.
METHODS
Using the search terms gender, sex, and sex differences in combination with cardiac electrophysiology, long QT syndrome, HERG, membrane transporters, and cytochromes, we conducted a systematic review of the available literature in the PubMed database. Relevant English- and French-language publications (to October 2007) on sex differences in LQTS were identified.
RESULTS
Clinical and experimental studies have reported that gonadal hormones play a role in sex-related differences of QT interval prolongation. Androgens may diminish drug effects on heart repolarization, and estrogens may facilitate arrhythmias. Furthermore, sex-related differences in the density of ion channels may partially explain this phenomenon. However, the magnitude of hormone-dependent differences observed in these studies remains very small compared with the large differences observed in clinical settings. Therefore, many scientists agree that the mechanisms responsible for sex-related differences in the risk of proarrhythmia from drugs remain largely undefined.
CONCLUSIONS
Other factors, such as sex-related modulation of drug disposition in situ, may fill the gaps in our understanding of the sex differences observed in drug-induced LQTS. We suggest that mechanisms such as the modulation of the pharmacokinetics of IKr (rapid component of the delayed rectifier potassium current) blockers, via modulation of intra- and extracellular concentrations, may be of major importance. Sex-specific changes in drug transport and metabolism will result in different plasma and intracellular levels acting along a dose-response effect on IKr block. Consequently, important hormone-dependent factors such as metabolic enzymes and membrane transporters need to be investigated in new basic research studies.
Topics: Animals; Causality; Cytochrome P-450 Enzyme System; Female; Gonadal Steroid Hormones; Humans; Long QT Syndrome; Membrane Transport Proteins; Potassium Channel Blockers; Risk Factors; Sex Characteristics; Sex Distribution; Sex Factors; Torsades de Pointes; Women's Health
PubMed: 18573480
DOI: 10.1016/j.genm.2008.05.005 -
Resuscitation Apr 2005We conducted a Medline search for controlled studies evaluating currently available drugs for pharmacological neuroprotection. They had to be administered prior to... (Review)
Review
We conducted a Medline search for controlled studies evaluating currently available drugs for pharmacological neuroprotection. They had to be administered prior to transient global cerebral ischaemia without further non-pharmacological measures. We deliberately excluded focal ischaemia since its pathophysiology is substantially different from global ischaemia. A total of 45 articles conducted exclusively in laboratory animals met these criteria. The following classes of agents were evaluated: anaesthetics, GABAergic drugs, calcium-antagonists, anticonvulsives, sodium-channel blockers, potassium-channel activators, NMDA-receptor antagonists, hormones, vasodilators, dopamine- and alpha2-agonists, magnesium, xanthine oxidase- and cyclooxygenase inhibitors, a nootropic, a protease inhibitor, and immunosuppressants. Some of them were applied chronically and others administered via clinically impracticable routes. The available literature favours isoflurane, phenytoin, lamotrigine, magnesium, and potentially, nimodipine, and flunarizine. If factors like costs, toxicity, side effects, route and mode of application are considered, isoflurane and MgSO4 that have also been safely applied to patients with compromised left ventricular pump function are advantageous but their true role in human neuroprotection remains unclear.
Topics: Animals; Brain Ischemia; Cardiovascular Agents; Central Nervous System Agents; Disease Models, Animal; Dopamine; Enzyme Inhibitors; Estradiol; Heart Arrest; Humans; Immunosuppressive Agents; Magnesium; Neuroprotective Agents; Neurotransmitter Agents; Potassium Channels; Progesterone; Receptors, N-Methyl-D-Aspartate
PubMed: 15797272
DOI: 10.1016/j.resuscitation.2004.11.004 -
Journal of Orthopaedic Surgery and... Mar 2024The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical... (Review)
Review
BACKGROUND
The lack of effective understanding of the pain mechanism of McCune-Albright syndrome (MAS) has made the treatment of pain in this disease a difficult clinical challenge, and new therapeutic targets are urgently needed to address this dilemma.
OBJECTIVE
This paper summarizes the novel mechanisms, targets, and treatments that may produce pain in MAS and fibrous dysplasia (polyfibrous dysplasia, or FD).
METHODS
We conducted a systematic search in the PubMed database, Web of Science, China Knowledge Network (CNKI) with the following keywords: "McCune-Albright syndrome (MAS); polyfibrous dysplasia (FD); bone pain; bone remodeling; G protein coupled receptors; GDNF family receptors; purinergic receptors and glycogen synthase kinase", as well as other keywords were systematically searched. Papers published between January 2018 and May 2023 were selected for finding. Initial screening was performed by reading the titles and abstracts, and available literature was screened against the inclusion and exclusion criteria.
RESULTS
In this review, we systematically analyzed the cutting-edge advances in this disease, synthesized the findings, and discussed the differences. With regard to the complete mechanistic understanding of the pain condition in FD/MAS, in particular, we collated new findings on new pathways, neurotrophic factor receptors, purinergic receptors, interferon-stimulating factors, potassium channels, protein kinases, and corresponding hormonal modulation and their respective strengths and weaknesses.
CONCLUSION
This paper focuses on basic research to explore FD/MAS pain mechanisms. New nonneuronal and molecular mechanisms, mechanically loaded responsive neurons, and new targets for potential clinical interventions are future research directions, and a large number of animal experiments, tissue engineering techniques, and clinical trials are still needed to verify the effectiveness of the targets in the future.
Topics: Animals; Fibrous Dysplasia, Polyostotic; Fibrous Dysplasia of Bone; Pain; Bone Remodeling; China
PubMed: 38515135
DOI: 10.1186/s13018-024-04687-y -
Disability and Rehabilitation Jul 2018To synthesise and critically appraise randomised controlled trials examining the effect of symptom-controlling medication on gait outcomes in people with multiple... (Review)
Review
PURPOSE
To synthesise and critically appraise randomised controlled trials examining the effect of symptom-controlling medication on gait outcomes in people with multiple sclerosis (MS).
METHOD
The literature search examined five databases (Medline, Embase, AMED, Cochrane (CENTRAL), and CINAHL until the end of November 2016. Eligible studies included medication to address symptoms associated with MS and an objective gait outcome measure. Two reviewers independently extracted data and assessed study quality using structured data extraction forms and the PEDro scale.
RESULTS
From 249 papers identified, 13 papers met inclusion criteria, examining three medications. Fampridine was found to significantly increase gait speed, but only in those people who responded to medication, which was less than half (pooled mean: 39%). Ten milligrams of fampridine twice daily significantly improves gait endurance. No definitive conclusions can be made about the efficacy of cannabinoid medication due to conflicting results across three studies. A single study of baclofen did not provide evidence to support the use of this medication to improve gait.
CONCLUSIONS
Limited evidence is available to guide gait symptom control for people with MS. Further research that includes three-dimensional gait analysis, patient perceived measures of gait dysfunction and explores combined efficacy of other modalities on gait is needed. Implications for Rehabilitation Gait disturbance is a common and disabling symptom of multiple sclerosis. Fampridine and cannabis medication may increase gait speed, baclofen does not. Fampridine can be used to improve gait endurance. Future research should include both quantitative and qualitative outcome measures of gait and investigate the combined efficacy of pharmacological and non-pharmacological interventions to assist clinicians to maximise gait improvements.
Topics: 4-Aminopyridine; Baclofen; Cannabinoids; Gait Disorders, Neurologic; Humans; Multiple Sclerosis; Muscle Relaxants, Central; Potassium Channel Blockers
PubMed: 28376639
DOI: 10.1080/09638288.2017.1309581 -
Frontiers in Neuroscience 2019The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a...
The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD. The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders. A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded. A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory. The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders.
PubMed: 31143096
DOI: 10.3389/fnins.2019.00445