-
Frontiers in Immunology 2023Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even... (Review)
Review
Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.
Topics: Animals; Humans; Sepsis; Acupuncture Therapy; Inflammation; Vagus Nerve
PubMed: 37753078
DOI: 10.3389/fimmu.2023.1242640 -
Obesity Reviews : An Official Journal... Nov 2023This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed... (Review)
Review
Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies.
This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for C-raclopride, F-fallypride, I-IBZM; one for dopamine transporter, I-FP-CIT; one used tracer for serotonin 5-HT receptor, F-altanserin; two used tracers for serotonin transporter, C-DASB or I-FP-CIT; two used tracer for μ-opioid receptor, C-carfentanil; one used tracer for noradrenaline transporter, C-MRB); seven studies assessed glucose uptake using F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using O-H O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using F-FTHA and one using C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies.
Topics: Humans; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Bariatric Surgery; Brain; Obesity; Neurotransmitter Agents
PubMed: 37699864
DOI: 10.1111/obr.13620 -
Phytomedicine : International Journal... Nov 2023Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative... (Review)
Review
BACKGROUND
Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression.
PURPOSE
In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value.
METHODS
This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar.
RESULTS
Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside.
CONCLUSIONS
These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.
Topics: Glycosides; Molecular Docking Simulation; Neuroprotection; Sequestosome-1 Protein
PubMed: 37657207
DOI: 10.1016/j.phymed.2023.155027 -
Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
Parkinsonism & Related Disorders Sep 2023The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH). (Review)
Review
BACKGROUND
The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH).
OBJECTIVES AND METHODS
We conducted a systematic review on the spectrum of movement disorders in PLH using standard terms for each of the phenomenologies and HIV.
RESULTS
Movement disorders in PLH were commonly attributed to opportunistic infections (OI), dopamine receptor blockade reactions, HIV-associated dementia (HAD), presented during seroconversion, developed due to drug reactions or antiretroviral therapy (ART) itself and lastly, movement disorders occurred as a consequence of the HIV-virus. Parkinsonism in ART naïve PLH was associated with shorter survival, however when Parkinsonism presented in PLH on ART, the syndrome was indistinguishable from Idiopathic Parkinson's disease and responded to therapy. Tremor was often postural due to HAD, drugs or OI. Generalized chorea was most frequent in HIV encephalopathy and toxoplasmosis gondii caused most cases of hemichorea. Ataxia was strongly associated with JCV infection, ART efavirenz toxicity or due to HIV itself. Dystonia was reported in HAD, secondary to drugs and atypical facial dystonias. Both cortical/subcortical and segmental/spinal origin myoclonus were noted mainly associated with HAD. In patients with HIV related opsoclonus-myoclonus-ataxia-syndrome, seroconversion illness was the commonest cause of followed by IRIS and CSF HIV viral escape phenomenon.
CONCLUSIONS
Aetiology of movement disorders in PLH depend on the treatment state. Untreated, PLH are prone to develop OI and HAD and movement disorders. However, as the number of PLH on ART increase and survive longer, the frequency of ART and non-AIDS related complications are likely to increase.
Topics: Humans; HIV; Myoclonus; Movement Disorders; HIV Infections; Parkinson Disease; Parkinsonian Disorders; Ataxia
PubMed: 37532621
DOI: 10.1016/j.parkreldis.2023.105774 -
The Journal of Clinical Psychiatry Jul 2023Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and...
Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data. Search terms included , , , , and . The process of study selection followed a previously published protocol and PRISMA guidelines. A total of 2,824 articles were identified through database search and 1 article via reference list check. Thirty-four studies were suitable for qualitative synthesis, and 13 studies were included in the quantitative analysis. Reviewers performed data extraction and quality assessment of the included studies independently following the review protocol. Evidence for a relationship between blood olanzapine level and efficacy/side effects (constipation) is considered low (Level C). In total, 3 studies of moderate quality consistently showed therapeutic thresholds of around 20 ng/mL for olanzapine 12 hours post-dose. This threshold is in line with findings from positron emission tomography (PET) studies that suggest optimal drug efficacy (65%-80% D-receptor occupancy) between 17 and 44 ng/mL. We suggest a therapeutic reference range of 20-40 ng/mL for olanzapine oral and LAI formulations. In this range, optimal treatment response is expected in patients with schizophrenia and schizophrenia spectrum disorders. Side effects, especially weight gain, may already occur at therapeutic levels. However, higher plasma concentrations are in general well tolerated and should not necessarily require a dose reduction in case of good response and tolerance.
Topics: Humans; Olanzapine; Antipsychotic Agents; Reference Values; Schizophrenia; Receptors, Dopamine D2; Benzodiazepines
PubMed: 37471567
DOI: 10.4088/JCP.22r14626 -
Frontiers in Neuroendocrinology Jul 2023The rapid and continual development of a number of radiopharmaceuticals targeting different receptor, enzyme and small molecule systems has fostered Positron Emission... (Review)
Review
The rapid and continual development of a number of radiopharmaceuticals targeting different receptor, enzyme and small molecule systems has fostered Positron Emission Tomography (PET) imaging of endocrine system actions in vivo in the human brain for several decades. PET radioligands have been developed to measure changes that are regulated by hormone action (e.g., glucose metabolism, cerebral blood flow, dopamine receptors) and actions within endocrine organs or glands such as steroids (e.g., glucocorticoids receptors), hormones (e.g., estrogen, insulin), and enzymes (e.g., aromatase). This systematic review is targeted to the neuroendocrinology community that may be interested in learning about positron emission tomography (PET) imaging for use in their research. Covering neuroendocrine PET research over the past half century, researchers and clinicians will be able to answer the question of where future research may benefit from the strengths of PET imaging.
Topics: Humans; Neuroendocrinology; Positron-Emission Tomography; Radiopharmaceuticals; Brain
PubMed: 37423505
DOI: 10.1016/j.yfrne.2023.101081 -
Frontiers in Neurology 2023Non-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs...
BACKGROUND
Non-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA is more potent than another. We performed a systematic review and network meta-analysis to evaluate the efficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD).
METHODS
Six NEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed.
RESULTS
A total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890).
CONCLUSIONS
In this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD.
PubMed: 37396766
DOI: 10.3389/fneur.2023.1183823 -
Expert Review of Clinical Pharmacology 2023Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have... (Review)
Review
INTRODUCTION
Olanzapine is widely used for treating schizophrenia and bipolar I disorder. Due to its high pharmacokinetic variability, several population pharmacokinetic studies have been performed to identify factors contributing to the variability and thus facilitate individualized dosing. This review aims to provide a comprehensive overview of published population pharmacokinetic studies and explore potential covariates.
METHODS
We systematically searched PubMed, Web of Science, and EMBASE databases from their inception to 31 December 2022. Information on the study design, characteristics, and final parameter estimates was summarized and compared. Monte Carlo simulations provided visual predictive distributions to compare eligible studies. Forest plots were constructed to explore the effects of covariates on olanzapine pharmacokinetics.
RESULTS
A total of 10 population pharmacokinetic and three population pharmacokinetic/pharmacodynamic studies involving infants, children, adolescents, and adults were finally included. The median apparent clearance was 0.253 L/h/kg in adults, 27-43% lower than that of infants and children. Men and smokers increased the apparent clearance of olanzapine by 32% and 34%, respectively. The concentration required to achieve half of the maximum effect for the Positive and Negative Syndrome Scale total score was 24.80 ng/mL, comparable with 22.32 ng/mL for dopamine D receptor occupancy.
CONCLUSIONS
A higher dosage may be required for men or heavy smokers than for women or nonsmokers to reach the same exposure. Moreover, further population studies are essential to be conducted to clarify the dose-exposure-response relationship of olanzapine.
PROSPERO REGISTRATION
CRD42022368637.
Topics: Male; Adult; Child; Infant; Adolescent; Humans; Female; Olanzapine; Antipsychotic Agents; Schizophrenia; Research Design; Models, Biological
PubMed: 37231707
DOI: 10.1080/17512433.2023.2219055 -
Brain and Behavior Jun 2023Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically... (Review)
Review
BACKGROUND
Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically proven, isolated dystonia syndrome. However, its pathophysiology remains unclear.
OBJECTIVES
This study was aimed at profiling the functional neuroimaging findings in DYT1 dystonia and harmonizing the pathophysiological implications for DYT1 dystonia from the standpoint of different neuroimaging techniques.
METHODS
A systematic review was conducted using identified studies published in English from Medline, PsycINFO, Embase, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR), between 1985 and December 2019 (PROSPERO protocol CRD42018111211).
RESULTS
All DYT1 gene carriers irrespective of clinical penetrance have reduced striatal GABA, dopamine receptors and increased metabolic activity in the lentiform nucleus, supplementary motor area, and cerebellum in addition to an abnormal cerebellothalamocortical pathway. Nonmanifesting carriers on the other hand have a disruption of the distal (thalamocortical) segment and have larger putaminal volumes than manifesting carriers and healthy controls. Activation of the midbrain, thalamus, and sensorimotor cortex was only found in the manifesting carriers.
CONCLUSIONS
Therefore, we propose that DYT1 dystonia is a cerebellostriatothalamocortical network disorder affecting either the structure or function of the different structures or nodes in the network.
Topics: Humans; Dystonia; Dystonic Disorders; Molecular Chaperones; Neuroimaging
PubMed: 37165749
DOI: 10.1002/brb3.3023