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The Cochrane Database of Systematic... Jun 2019Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.
OBJECTIVES
To assess the effects of ALC for the treatment of DPN.
SEARCH METHODS
On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods.
MAIN RESULTS
We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P = 0.17). The other two placebo-controlled studies reported no dropouts due to adverse events, and more pain, paraesthesia, and hyperaesthesias in the placebo group than the 3000 mg/day ALC group, but provided no numerical data. The overall certainty of adverse event evidence for the comparison of ALC versus placebo was low.The study comparing ALC with methylcobalamin reported that 34/117 participants (29.1%) experienced adverse events in the ALC group versus 33/115 (28.7%) in the methylcobalamin group (P = 0.95). Nine participants discontinued treatment due to adverse events (ALC: 4 participants, methylcobalamin: 5 participants), which were most commonly gastrointestinal symptoms. The certainty of the adverse event evidence for ALC versus methylcobalamin was low.Two studies were funded by the manufacturer of ALC and the other two studies had at least one co-author who was a consultant for an ALC manufacturer.
AUTHORS' CONCLUSIONS
We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.
Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12
PubMed: 31201734
DOI: 10.1002/14651858.CD011265.pub2 -
Molecular Psychiatry Mar 2012A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First,... (Meta-Analysis)
Meta-Analysis Review
A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.
Topics: Adenosine Triphosphate; Adolescent; Animals; Biomarkers; Brain; Child; Child Development Disorders, Pervasive; Comorbidity; Developmental Disabilities; Disease Models, Animal; Electron Transport; Energy Metabolism; Female; Gastrointestinal Diseases; Humans; Lactates; Male; Mitochondria; Mitochondrial Diseases; Neuroimaging; Prevalence; Pyruvic Acid; Seizures; Sex Distribution; Young Adult
PubMed: 21263444
DOI: 10.1038/mp.2010.136 -
Molecules (Basel, Switzerland) Jan 2023We provide a systematic overview of the mechanochemical reactions of inorganic solids, notably simple binary compounds, such as oxides, nitrides, carbides, sulphides,... (Review)
Review
We provide a systematic overview of the mechanochemical reactions of inorganic solids, notably simple binary compounds, such as oxides, nitrides, carbides, sulphides, phosphides, hydrides, borides, borane derivatives, and related systems. Whereas the solid state has been traditionally considered to be of little synthetic value by the broader community of synthetic chemists, the solid-state community, and in particular researchers focusing on the reactions of inorganic materials, have thrived in building a rich and dynamic research field based on mechanically-driven transformations of inorganic substances typically seen as inert and high-melting. This review provides an insight into the chemical richness of such mechanochemical reactions and, at the same time, offers their tentative categorisation based on transformation type, resulting in seven distinct groupings: () the formation of adducts, () the reactions of dehydration; () oxidation-reduction (redox) reactions; () metathesis (or exchange) reactions; () doping and structural rearrangements, including reactions involving the reaction vessel (the milling jar); () acid-base reactions, and () other, mixed type reactions. At the same time, we offer a parallel description of inorganic mechanochemical reactions depending on the reaction conditions, as those that: () take place under mild conditions (e.g., manual grinding using a mortar and a pestle); () proceed gradually under mechanical milling; () are self-sustained and initiated by mechanical milling, i.e., mechanically induced self-propagating reactions (MSRs); and () proceed only via harsh grinding and are a result of chemical reactivity under strongly non-equilibrium conditions. By elaborating on typical examples and general principles in the mechanochemistry of hard and high-melting substances, this review provides a suitable complement to the existing literature, focusing on the properties and mechanochemical reactions of inorganic solids, such as nanomaterials and catalysts.
Topics: Catalysis; Nanostructures; Oxidation-Reduction; Oxides
PubMed: 36677953
DOI: 10.3390/molecules28020897 -
The Science of the Total Environment Jun 2020The fate and transport of Hg species in natural aquatic environment are strongly affected by photochemical transformation of Hg, Hg, and MeHg. Migration of Hg is... (Review)
Review
The fate and transport of Hg species in natural aquatic environment are strongly affected by photochemical transformation of Hg, Hg, and MeHg. Migration of Hg is determined by its complexation with organic and inorganic ligands that are widely present in the water. The presence of dissolved organic matter (DOM) is closely related to photochemical reactions of Hg. DOM can strongly bind to mercury (e.g., Hg and MeHg), thus affecting its speciation, mobility and toxicity, eventually dominating its bioavailability. This review summarizes extensive studies on photochemical behaviors of Hg including: (1) photo-oxidation; (2) photo-reduction; (3) photochemical methylation; and (4) MeHg photo-degradation. Photo-oxidation of Hg is mostly caused by oxidative free radicals (e.g., •OH, CO, O, and O), while photo-reduction of Hg is more complicated and it involves two pathways: (1) primary processes (direct photolysis of Hg or ligand-metal charge transfer of Hg-DOM complex); and (2) secondary processes (reduction of Hg-DOM complex induced by free radicals derived from DOM photolysis). Photochemical methylation of inorganic Hg occurs as follows: (1) Hg complexes with methyl donors (e.g., acetic acid, tert-butyl, alcohols, etc.) to form intermediates, followed by (2) an intramolecular methyl transfer. MeHg photo-degradation is the leading pathway for MeHg demethylation and it primarily proceeds via four different pathways. The information on DOM was also mentioned, but DOM is not the only factor that affects the photochemical behaviors of Hg. Other influencing factors such as: (1) pH value; (2) dissolved oxygen; (3) cations (Fe, K) and anions (NO, HCO, CO, Cl); and (4) suspended substance cannot be ignored.
PubMed: 32143045
DOI: 10.1016/j.scitotenv.2020.137540 -
Biological Trace Element Research Mar 2017In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of... (Meta-Analysis)
Meta-Analysis Review
In this meta-analysis, studies reporting arsenic-induced oxidative damage in mouse models were systematically evaluated to provide a scientific understanding of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight relevant peer-reviewed publications were identified through exhaustive database searching. Oxidative stress indexes assessed included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG), malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis showed that arsenic exposure generally suppressed measured levels of the antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels increased to a significantly (P < 0.05) greater extent upon exposure to As than to As. Other factors that contributed to a greater overall oxidative effect from arsenic exposure included intervention time, intervention method, dosage, age of animals, and the sample source from which the indexes were estimated. Our meta-analysis effectively summarized a wide range of studies and detected a positive relationship between arsenic exposure and oxidative damage. These data provide a scientific basis for the prevention and treatment of arsenic poisoning.
Topics: Age Factors; Animals; Antioxidants; Arsenic; Arsenic Poisoning; Catalase; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Malondialdehyde; Mice; Oxidation-Reduction; Oxidative Stress; Rats; Reactive Oxygen Species; Regression Analysis; Superoxide Dismutase; Time Factors
PubMed: 27498811
DOI: 10.1007/s12011-016-0810-4 -
Oxidative Medicine and Cellular... 2016Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue... (Review)
Review
Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD.
Topics: Animals; Antioxidants; Humans; Kidney; Lipid Peroxidation; Oxidation-Reduction; Oxidative Stress; Prognosis; Protein Carbonylation; Reactive Oxygen Species; Renal Insufficiency, Chronic
PubMed: 27563376
DOI: 10.1155/2016/8598253 -
NeuroImage. Clinical 2023Aging is characterized by a gradual decline of the body's biological functions, which can lead to increased production of reactive oxygen species (ROS). Antioxidants... (Review)
Review
Aging is characterized by a gradual decline of the body's biological functions, which can lead to increased production of reactive oxygen species (ROS). Antioxidants neutralize ROS and maintain balance between oxidation and reduction. If ROS production exceeds the ability of antioxidant systems to neutralize, a damaging state of oxidative stress (OS) may exist. The reduced form of glutathione (GSH) is the most abundant antioxidant, and decline of GSH is considered a marker of OS. Our review summarizes the literature on GSH variations with age in healthy adults in brain (in vivo, ex vivo) and blood (plasma, serum), and reliability of in vivo magnetic resonance spectroscopy (MRS) measurement of GSH. A systematic PubMed search identified 35 studies. All in vivo MRS studies (N = 13) reported good to excellent reproducibility of GSH measures. In brain, 3 out of 4 MRS studies reported decreased GSH with age, measured in precuneus, cingulate, and occipital regions, while 1 study reported increased GSH with age in frontal and sensorimotor regions. In post-mortem brain, out of 3 studies, 2 reported decreased GSH with age in hippocampal and frontal regions, while 1 study reported increased GSH with age in a frontal region. Oxidized glutathione disulfide (GSSG) was reported to be increased in caudate with age in 1 study, suggesting OS. Although findings in the brain lacked a clear consensus, the majority of studies suggested a decline of GSH with age. The low number of studies (particularly ex vivo) and potential regional differences may have contributed to variability in the findings in brain. In blood, in contrast, GSH levels predominately were reported to decrease with advancing age (except in the oldest-old, who may represent a select group of particularly successful agers), while GSSG findings lacked consensus. The larger number of studies assessing age-specific GSH level changes in blood (N = 16) allowed for more robust consensus across studies than in brain. Overall, the literature suggests that aging is associated with increased OS in brain and body, but the timing and regional distribution of changes in the brain require further study. The contribution of brain OS to brain aging, and the effect of interventions to raise brain GSH levels on decline of brain function, remain understudied. Given that reliable tools to measure brain GSH exist, we hope this paper will serve as a catalyst to stimulate more work in this field.
Topics: Humans; Adult; Aged, 80 and over; Antioxidants; Glutathione Disulfide; Reproducibility of Results; Reactive Oxygen Species; Glutathione; Brain
PubMed: 37742519
DOI: 10.1016/j.nicl.2023.103503 -
Neurochemical Research Jul 2022Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (CHOS) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid,... (Review)
Review
Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (CHOS) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid, DHLA) form of LA. α-LA is a potent anti-oxidative agent that has a significant potential to treat neurodegenerative disorders. α-LA is both hydrophilic and hydrophobic in nature. It is widely distributed in plants and animals in cellular membranes and in the cytosol, which is responsible for LA's action in both the cytosol and plasma membrane. A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the α-Lipoic acid for central nervous system diseases. Moreover, α-LA readily crosses the blood-brain barrier, which is a significant factor for CNS activities. The mechanisms of α-LA reduction are highly tissue-specific. α-LA produces its neuroprotective effect by inhibiting reactive oxygen species formation and neuronal damage, modulating protein levels, and promoting neurotransmitters and anti-oxidant levels. Hence, the execution of α-LA as a therapeutic ingredient in the therapy of neurodegenerative disorders is promising. Finally, based on evidence, it can be concluded that α-LA can prevent diseases related to the nervous system.
Topics: Animals; Antioxidants; Neurodegenerative Diseases; Neuroprotective Agents; Oxidation-Reduction; Thioctic Acid
PubMed: 35445914
DOI: 10.1007/s11064-022-03598-w -
Environmental Science and Pollution... Jun 2022Antineoplastic agents present potential hazards to human health and the environment. For this reason, these compounds have attracted a great deal of attention from... (Review)
Review
Trends in Fenton and photo-Fenton processes for degradation of antineoplastic agents in water matrices: current knowledge and future challenges evaluation using a bibliometric and systematic analysis.
Antineoplastic agents present potential hazards to human health and the environment. For this reason, these compounds have attracted a great deal of attention from researchers in the environmental sciences field. In order to help guide future research, it is important to understand the current state of investigation of the occurrence of these microcontaminants and methods for their removal, especially focusing on Fenton and photo-Fenton processes applied to various aqueous matrices in which this class of pharmaceuticals is present. For this purpose, a systematic review of these topics was performed by bibliometric analysis of articles published during the last decade and available in the Scopus and Web of Science databases. This study enables visualization of the current panorama and trends in this field, providing a guide for future collaborative research and exchange of knowledge. Various strategies have been suggested to improve the efficiency of Fenton and photo-Fenton processes, mainly by means of the application of multiples additions of iron, the use of heterogeneous catalysts, and/or the use of chelating agents. Some studies have evaluated different radiation sources employed for photo-Fenton processes, such as solar and/or artificial radiation. In turn, the identification of transformation products generated by Fenton and photo-Fenton treatments, together with their evaluation by in silico (Q)SAR predictions or experimental toxicological bioassays, are related subjects that have been less reported in published works and that should be studied in depth. These subjects can support treatment evaluations that are more realistic, considering their limitations or potentials.
Topics: Antineoplastic Agents; Bibliometrics; Humans; Hydrogen Peroxide; Oxidation-Reduction; Water; Water Pollutants, Chemical
PubMed: 34403053
DOI: 10.1007/s11356-021-15938-4 -
Actas Dermo-sifiliograficas May 2017Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the... (Meta-Analysis)
Meta-Analysis Review
Actinic keratosis is a precursor lesion to the most common nonmelanoma skin cancer. Conventional photodynamic therapy (PDT) has been shown to be effective, but the procedure is time-consuming, can be very painful, and requires infrastructure. These shortcomings led to the emergence of daylight PDT. To obtain a global estimate of efficacy, we undertook a systematic literature review and performed a meta-analysis of the available evidence on the efficacy and safety of daylight PDT as compared to conventional PDT in the treatment of actinic keratosis and/or field cancerization. The conclusion is that the difference in efficacy is clinically negligible (global estimate of the mean response rate difference, -3.69%; 95% CI, -6.54% to -0.84%). The adverse effects of daylight PDT are mild and localized (79% of patients report no discomfort), and patients report less pain (P<.001). Daylight PDT gives good to excellent cosmetic results in more than 90% of patients, and patient satisfaction is greater (P<.001).
Topics: Carcinoma, Squamous Cell; Clinical Trials, Phase III as Topic; Esthetics; Humans; Keratosis, Actinic; Neoplasms, Radiation-Induced; Oxidation-Reduction; Pain; Patient Satisfaction; Photochemistry; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Sunlight; Ultraviolet Rays
PubMed: 28063524
DOI: 10.1016/j.ad.2016.09.020