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Scientific Reports Aug 2020Myopic anisometropia (anisomyopia) is a specific type of refractive error that may cause fusion impairment, asthenopia, and aniseikonia. It is sometimes severe enough to... (Comparative Study)
Comparative Study
Myopic anisometropia (anisomyopia) is a specific type of refractive error that may cause fusion impairment, asthenopia, and aniseikonia. It is sometimes severe enough to reduce the quality of life. Several studies have investigated the treatment effects of orthokeratology (Ortho-K) and topical atropine on anisomyopia control. However, no study has compared these two interventions simultaneously until now. The cohort of this retrospective study included 124 children with anisomyopia who were treated with binocular Ortho-K lenses, 0.01% atropine, or 0.05% atropine. After a 2-year follow-up, the inter-eye difference in axial length (AL) significantly decreased in the Ortho-K group (P = 0.015) and remained stable in the two atropine groups. When comparing the myopia control effect, the use of Ortho-K lenses resulted in an obviously smaller change in AL than the use of 0.01% and 0.05% atropine (P < 0.01). Ortho-K treatment may reduce the degree of anisomyopia and stabilise the progression of myopia. Hence, Ortho-K might be a better choice for anisomyopic children.
Topics: Adolescent; Anisometropia; Atropine; Axial Length, Eye; Child; Child, Preschool; Disease Progression; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Muscarinic Antagonists; Myopia; Orthokeratologic Procedures; Retrospective Studies; Treatment Outcome
PubMed: 32843658
DOI: 10.1038/s41598-020-71142-3 -
Scientific Reports Dec 2022Myopia is a leading cause of visual impairment in young people worldwide. It sometimes increases the risk of blindness and reduces life quality. Previous reports have...
Myopia is a leading cause of visual impairment in young people worldwide. It sometimes increases the risk of blindness and reduces life quality. Previous reports have revealed the treatment effects of defocus-incorporated multiple segments (DIMS) and topical atropine (ATP) on myopia control. However, no study has evaluated these two interventions together. In this retrospective study, we aimed to determine whether the combination of DIMS lenses and 0.01% ATP can slow the progression of myopia compared with DIMS lenses or single vision (SV) lenses alone. We included 107 children with myopia who were treated with DIMS and 0.01% ATP combination (DIMS + ATP group), DIMS monotherapy (DIMS group), or a control group (SV group). We compared treatment effects among three groups in axial length and myopia progression. After a 1-year follow-up, the DIMS + ATP group showed a smaller change in axial length and myopia progression than the DIMS and SV groups (P < 0.05). Hence, combination treatment with DIMS and 0.01% ATP might be a better choice for children with myopia.
Topics: Child; Humans; Adolescent; Atropine; Retrospective Studies; Refraction, Ocular; Myopia; Eyeglasses; Adenosine Triphosphate; Disease Progression
PubMed: 36566245
DOI: 10.1038/s41598-022-25599-z -
Acta Medica Okayama Aug 2022To clarify the preventive effects of 0.01% atropine eye drops against myopia progression and axial elongation in children, a meta-analysis was carried out based on data... (Meta-Analysis)
Meta-Analysis
To clarify the preventive effects of 0.01% atropine eye drops against myopia progression and axial elongation in children, a meta-analysis was carried out based on data obtained from PubMed and Web of Science as of August 1, 2021. Randomized controlled trials (RCTs) that enrolled myopic children who had received atropine for at least one year were included in this study, Key search terms included myopia, children, and 0.01% or low-dose atropine. Heterogeneity was quantified by I2 statistics, and meta-analyses were performed using the fixed-effect model. Five RCTs involving 809 unique children were analyzed. One trial was excluded because of a poor Jadad score and markedly rapid myopia progression in controls. The mean effect sizes for 12 months in myopia progression and axial elongation synthesized from the remaining 4 RCTs were 0.20 (95% CI: 0.13 to 0.27) D and -0.08 (-0.11 to -0.04) mm, respectively (p<0.0001). The corresponding inhibition ratios were 28% and 19%. I2 statistics were 6% or less. Sensitivity analysis and funnel plots demonstrated the robustness of the estimation. The 0.01% atropine-induced inhibition ratio for myopia progression in Asian children was roughly half of that originally reported and did not reach the minimum requirement for clinical treatment.
Topics: Atropine; Child; Disease Progression; Humans; Myopia; Ophthalmic Solutions; Randomized Controlled Trials as Topic
PubMed: 36123161
DOI: 10.18926/AMO/63905 -
Proceedings of the National Academy of... Apr 2023The tropane alkaloids (TAs) cocaine and hyoscyamine have been used medicinally for thousands of years. To understand the evolutionary origins and trajectories of serial...
The tropane alkaloids (TAs) cocaine and hyoscyamine have been used medicinally for thousands of years. To understand the evolutionary origins and trajectories of serial biosynthetic enzymes of TAs and especially the characteristic tropane skeletons, we generated the chromosome-level genome assemblies of cocaine-producing (Erythroxylaceae, rosids clade) and hyoscyamine-producing (Solanaceae, asterids clade). Comparative genomic and phylogenetic analysis suggested that the lack of spermidine synthase/-methyltransferase (SPMT1) in ancestral asterids species contributed to the divergence of polyamine (spermidine or putrescine) methylation in cocaine and hyoscyamine biosynthesis. Molecular docking analysis and key site mutation experiments suggested that ecgonone synthases CYP81AN15 and CYP82M3 adopt different active-site architectures to biosynthesize the same product ecgonone from the same substrate in Erythroxylaceae and Solanaceae. Further synteny analysis showed different evolutionary origins and trajectories of CYP81AN15 and CYP82M3, particularly the emergence of through the neofunctionalization of ancient tandem duplication genes. The combination of structural biology and comparative genomic analysis revealed that ecgonone methyltransferase, which is responsible for the biosynthesis of characteristic 2-substituted carboxymethyl group in cocaine, evolved from the tandem copies of salicylic acid methyltransferase by the mutations of critical E216 and S153 residues. Overall, we provided strong evidence for the independent origins of serial TA biosynthetic enzymes on the genomic and structural level, underlying the chemotypic convergence of TAs in phylogenetically distant species.
Topics: Hyoscyamine; Phylogeny; Molecular Docking Simulation; Tropanes; Solanaceae; Genomics; Cocaine; Methyltransferases
PubMed: 37068250
DOI: 10.1073/pnas.2302448120 -
Ophthalmic Research 2022Myopia is usually caused by excessive elongation of the eye during development. This condition is common worldwide. In clinical practice, the progression of myopia is...
INTRODUCTION
Myopia is usually caused by excessive elongation of the eye during development. This condition is common worldwide. In clinical practice, the progression of myopia is commonly controlled through optical or drug measures, but the specific mechanisms underlying these two treatments remain unclear. To verify whether the effects of these two treatments on posterior-pole tissues are similar or different, we studied a set of common transcriptional changes in chicken models.
METHODS
Chicks were divided into four groups, and they were given the intervention measures of plus-lens induction, minus-lens induction, minus-lens induction with atropine injection, and minus-lens induction with saline injection. Then, the genetic changes in each tissue at the posterior pole were detected, and the results of different genes were compared. A semiquantitative real-time polymerase chain reaction method was used to further study the visually induced changes in the transcription of potential candidate genes.
RESULTS
Based on RNA sequencing (RNA-seq) analysis of the transcriptome, we identified variations between the differentially expressed transcripts in three tissues from the two treatment groups. Through Kyoto Encyclopedia of Genes and Genomes enrichment analyses, eukaryotic protein translation elongation factor 1α2 (EEF1A2) was enriched in the "leishmaniasis" pathway in the choroid and showed increased expression in both the plus-lens induction and injection atropine groups. The expression levels of selected genes verified by quantitative real-time PCR were concordant with the RNA-seq data.
CONCLUSIONS
Overlapping differentially expressed mRNAs of only one-tenth could suggest a different mechanism of myopic defocus and intravitreal injection of atropine controlling myopia. EEF1A2 might play an important role in the choroid during the treatment of myopia.
Topics: Animals; Atropine; Chickens
PubMed: 35797963
DOI: 10.1159/000525744 -
British Journal of Pharmacology Mar 2022Gastric pacemaker cells, interstitial cells of Cajal (ICC), are believed to initiate myogenic (non-neuronal) contractions. These become damaged in gastroparesis,...
BACKGROUND AND PURPOSE
Gastric pacemaker cells, interstitial cells of Cajal (ICC), are believed to initiate myogenic (non-neuronal) contractions. These become damaged in gastroparesis, associated with dysrhythmic electrical activity and nausea. We utilised mouse isolated stomach to model myogenic contractions and investigate their origin and actions of interstitial cells of Cajal modulators.
EXPERIMENTAL APPROACH
Intraluminal pressure was recorded following distension with a physiological volume; tone, contraction amplitude and frequency were quantified. Compounds were bath applied.
KEY RESULTS
The stomach exhibited regular large amplitude contractions (median amplitude 9.0 [4.7-14.8] cmH O, frequency 2.9 [2.5-3.4] c.p.m; n = 20), appearing to progress aborally. Tetrodotoxin (TTX, 10 M) had no effect on tone, frequency or amplitude but blocked responses to nerve stimulation. ω-conotoxin GVIA (10 M) ± TTX was without effect on baseline motility. In the presence of TTX, (1) atropine (10 -10 M) reduced contraction amplitude and frequency in a concentration-related manner (pIC 7.5 ± 0.3 M for amplitude), (2) CaCC channel (previously ANO1) inhibitors MONNA and CaCCinh-A01 reduced contraction amplitude (significant at 10 , 10 M respectively) and frequency (significant at 10 M), and (3), neostigmine (10 M) evoked a large, variable, increase in contraction amplitude, reduced by atropine (10 -10 M) but unaffected (exploratory study) by the H1 receptor antagonist mepyramine (10 M).
CONCLUSIONS AND IMPLICATIONS
The distended mouse stomach exhibited myogenic contractions, resistant to blockade of neural activity by TTX. In the presence of TTX, these contractions were prevented or reduced by compounds blocking interstitial cells of Cajal activity or by atropine and enhanced by neostigmine (antagonised by atropine), suggesting involvement of non-neuronal ACh in their regulation.
Topics: Acetylcholine; Animals; Atropine; Electric Stimulation; Mice; Muscle Contraction; Neostigmine; Stomach; Tetrodotoxin
PubMed: 34519057
DOI: 10.1111/bph.15685 -
Toxicology Letters Jun 2024Animal research continues to serve a critical role in the testing and development of medical countermeasures. The Göttingen minipig, developed for laboratory research,...
Animal research continues to serve a critical role in the testing and development of medical countermeasures. The Göttingen minipig, developed for laboratory research, may provide many benefits for addressing research questions within chemical defense. Targeted development of the Göttingen minipig model could reduce reliance upon non-human primates, and improve study design, statistical power, and throughput to advance medical countermeasures for regulatory approval and fielding. In this vein, we completed foundational pharmacokinetics and physiological safety studies of intramuscularly administered atropine sulfate, pralidoxime chloride (2-PAM), and diazepam across a broad range of doses (1-6 autoinjector equivalent) using adult male Göttingen minipigs (n=11; n=4-8/study) surgically implanted with vascular access ports and telemetric devices to monitor cardiovascular, respiratory, arterial pressure, and temperature signals. Pharmacokinetic data were orderly and the concentration maximum mirrored available human data at comparably scaled doses clearly for atropine, moderately for 2-PAM, and poorly for diazepam. Time to peak concentration approximated 2, 7, and 20 min for atropine, 2-PAM, and diazepam, respectively, and the elimination half-life of these drugs approximated 2 hr (atropine), 3 hr (2-PAM), and 8 hr (diazepam). Atropine sulfate dose-dependently increased the magnitude and duration of tachycardia and decreased the PR and ST intervals (consistent with findings obtained from other species). Mild hypothermia was observed at the highest diazepam dose. Göttingen minipigs appear to provide a ready and appropriate large animal alternative to non-human primates, and further development and evaluation of novel nerve agent medical countermeasures and treatment strategies in this model are justified.
Topics: Animals; Swine, Miniature; Swine; Male; Diazepam; Atropine; Nerve Agents; Dose-Response Relationship, Drug; Injections, Intramuscular; Half-Life; Heart Rate; Telemetry; Models, Animal; Pralidoxime Compounds
PubMed: 38703967
DOI: 10.1016/j.toxlet.2024.04.014 -
Acta Medica (Hradec Kralove) 2022Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects....
Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects. The aim of the study was to analyse the clinical signs of acute paraoxon poisoning in rats and to determine the relationship between the intensity of signs of poisoning and the dose of paraoxon and/or the outcome of poisoning in rats. Animals were treated with either saline or atropine (10 mg/kg intramuscularly). The median subcutaneous lethal dose (LD50) of paraoxon was 0.33 mg/kg and protective ratio of atropine was 2.73. The presence and intensity of signs of poisoning in rats (dyspnoea, lacrimation, exophthalmos, fasciculations, tremor, ataxia, seizures, piloerection, stereotypic movements) were observed and recorded for 4 h after the injection of paraoxon. Intensity of these toxic phenomena was evaluated as: 0 - absent, 1 - mild/moderate, 2 - severe. Fasciculations, seizures and tremor were more intense at higher doses of paraoxon and in non-survivors. In unprotected rats piloerection occurred more often and was more intense at higher doses of paraoxon as well as in non-survivors. In atropine-protected rats, piloerection did not correlate with paraoxon dose or outcome of poisoning. The intensity of fasciculations and seizures were very strong prognostic parameters of the poisoning severity.
Topics: Acetylcholinesterase; Animals; Atropine; Fasciculation; Paraoxon; Rats; Seizures; Tremor
PubMed: 35793503
DOI: 10.14712/18059694.2022.10 -
Clinical & Experimental Optometry Sep 2010Treatment for amblyopia commonly involves passive methods such as occlusion of the non-amblyopic eye. An evidence base for these methods is provided by animal models of... (Review)
Review
Treatment for amblyopia commonly involves passive methods such as occlusion of the non-amblyopic eye. An evidence base for these methods is provided by animal models of visual deprivation and plasticity in early life and randomised controlled studies in humans with amblyopia. Other treatments of amblyopia, intended to be used instead of or in conjunction with passive methods, are known as 'active' because they require some activity on the part of the patient. Active methods are intended to enhance treatment of amblyopia in a number of ways, including increased compliance and attention during the treatment periods (due to activities that are interesting for the patient) and the use of stimuli designed to activate and to encourage connectivity between certain cortical cell types. Active methods of amblyopia treatment are widely available and are discussed to some extent in the literature, but in many cases the evidence base is unclear, and effectiveness has not been thoroughly tested. This review looks at the techniques and evidence base for a range of these methods and discusses the need for an evidence-based approach to the acceptance and use of active amblyopia treatments.
Topics: Amblyopia; Animals; Atropine; Humans; Orthoptics; Phototherapy
PubMed: 20533925
DOI: 10.1111/j.1444-0938.2010.00486.x -
Medicine May 2022This meta-analysis aimed to identify the therapeutic effect of 0.01% atropine with orthokeratology on ocular axial elongation for myopia children. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis aimed to identify the therapeutic effect of 0.01% atropine with orthokeratology on ocular axial elongation for myopia children.
METHODS
We searched PubMed, Cochrane Library, and CBM databases from inception to July 1st, 2021. Meta-analysis was conducted using STATA version 14.0 and Review Manager version 5.3 softwares. We calculated the weighted mean differences to analyze the change of ocular axial length (AL) between orthokeratology combined with 0.01% atropine (OKA) and) alone. The Cochran's Q-statistic and I2 test were used to evaluate potential heterogeneity between studies. To evaluate the influence of single studies on the overall estimate, a sensitivity analysis was performed. We also performed sub group and meta-regression analyses to investigate potential sources of heterogeneity. We conducted Begger funnel plots and Egger linear regression tests to investigate publication bias.
RESULTS
Nine studies that met all inclusion criteria were included in this meta-analysis. A total of 191 children in OKA group and 196 children in orthokeratology (OK) group were assessed. The pooled summary weighted mean differences of AL change was -0.90 (95% CI = -1.25-0.55) with statistical significance (t = -5.03, P < .01), which indicated there was obvious difference between OKA and OK in myopic children. Subgroup analysis also showed that OKA treatment resulted in significantly less axial elongation compared to OK treatment alone according to SER. We found no evidence for publication bias.
CONCLUSIONS
Our meta-analysis indicates 0.01% atropine atropine is effective in slowing axial elongation in myopia children with orthokeratology.
Topics: Atropine; Axial Length, Eye; Child; Ear Diseases; Humans; Myopia; Orthokeratologic Procedures; Refraction, Ocular
PubMed: 35550467
DOI: 10.1097/MD.0000000000029191