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Andes Pediatrica : Revista Chilena de... Oct 2021Accidental or intentional intoxication by organophosphates, which are toxic substances that inhibit acetylcholinesterase, constitutes a serious public health problem...
INTRODUCTION
Accidental or intentional intoxication by organophosphates, which are toxic substances that inhibit acetylcholinesterase, constitutes a serious public health problem worldwide, with a greater impact in developing countries. Chronic intoxication during pregnancy with alterations in neurodevelopment and fetal growth has been described.
OBJECTIVE
To describe an unusual case of transplacentally acquired organophosphorus poisoning, highlighting the clinical presentation, the management with atropine, and the neurological outcome.
CLINICAL CASE
36-weeks premature newborn, whose mother presented acute intentional organophosphorus poisoning 17 hours before birth. The patient was born by emergency C-section, without respiratory distress, with bradycardia, hypotonia, miosis, and bron- chorrhea, as well as clinical signs and laboratory evidence of acute poisoning, with severe metabolic acidosis, and decreased cholinesterase activity. She required advanced resuscitation, management in the Neonatal Intensive Care Unit with invasive ventilation, inotropes, and repeated doses of atropine. She evolved with left hemiparesis and convulsive syndrome that was treated with phenobarbital. She was discharged at 34 days of life with her mother, under custody and supervision of social and family welfare. Treatment and follow-up were suspended until her first year of life when her custody was transferred to an aunt. In neurological control at 18 months, she presented persistence of hemiparesis and speech-language delay, without new seizures.
CONCLUSIONS
Organophosphorus poisoning is very rare in the neonatal period and due to the absence of guidelines for the management of this type of patients its treatment is challenging and must be individualized, multidisciplinary, evaluating the risk and benefit of each intervention.
Topics: Acetylcholinesterase; Atropine; Cholinesterases; Female; Humans; Infant, Newborn; Organophosphate Poisoning; Organophosphates; Pregnancy
PubMed: 35319584
DOI: 10.32641/andespediatr.v92i5.3275 -
Nature Sep 2020Tropane alkaloids from nightshade plants are neurotransmitter inhibitors that are used for treating neuromuscular disorders and are classified as essential medicines by...
Tropane alkaloids from nightshade plants are neurotransmitter inhibitors that are used for treating neuromuscular disorders and are classified as essential medicines by the World Health Organization. Challenges in global supplies have resulted in frequent shortages of these drugs. Further vulnerabilities in supply chains have been revealed by events such as the Australian wildfires and the COVID-19 pandemic. Rapidly deployable production strategies that are robust to environmental and socioeconomic upheaval are needed. Here we engineered baker's yeast to produce the medicinal alkaloids hyoscyamine and scopolamine, starting from simple sugars and amino acids. We combined functional genomics to identify a missing pathway enzyme, protein engineering to enable the functional expression of an acyltransferase via trafficking to the vacuole, heterologous transporters to facilitate intracellular routing, and strain optimization to improve titres. Our integrated system positions more than twenty proteins adapted from yeast, bacteria, plants and animals across six sub-cellular locations to recapitulate the spatial organization of tropane alkaloid biosynthesis in plants. Microbial biosynthesis platforms can facilitate the discovery of tropane alkaloid derivatives as new therapeutic agents for neurological disease and, once scaled, enable robust and agile supply of these essential medicines.
Topics: Acyltransferases; Alkaloids; Animals; Atropa belladonna; Atropine Derivatives; Biological Transport; Datura; Glucosides; Hyoscyamine; Lactates; Ligases; Models, Molecular; Nervous System Diseases; Oxidoreductases; Protein Engineering; Saccharomyces cerevisiae; Scopolamine; Vacuoles
PubMed: 32879484
DOI: 10.1038/s41586-020-2650-9 -
Frontiers in Public Health 2023To compare the myopic progression in children treated with 0. 01% atropine and those who discontinued atropine during the 2022-home quarantine in Shanghai.
PURPOSE
To compare the myopic progression in children treated with 0. 01% atropine and those who discontinued atropine during the 2022-home quarantine in Shanghai.
METHODS
In this retrospective study, children aged 6-13 years with follow-up visits before (between January 2022 and February 2022) and after the lockdown (between July 2022 and August 2022) were included. Cycloplegic refraction and axial length (AL) were measured at both visits. The atropine group had continuous medication during the lockdown while the control group discontinued. The 0.01% atropine eyedrops were administered daily before bedtime. The types of spectacle lens were recorded: single vision (SV) spectacles or defocus incorporated multiple segments lenses (DIMS).
RESULTS
In total, 41 children (81 eyes) in the atropine group and 32 children (64 eyes) in the control group were enrolled. No significant difference was found in the demographic characteristics, spherical diopter, spherical equivalent (SE), AL, and follow-up time between the two groups before the lockdown in 2022 (all > 0.1). After the home confinement, a greater myopia progression was observed in the control group (-0.46 ± 0.42 D) compared to atropine group (-0.26 ± 0.37 D; = 0.0023). Axial elongation was also longer in the control group than that in children sustained with atropine (0.21 ± 0.17 vs. 0.13 ± 0.15 mm, = 0.0035). Moreover, there was no significant change of spherical diopter and SE during lockdown in the atropine + DIMS combined subgroup (0.03 ± 0.033 D for spherical diopter, = 0.7261 and 0.08 ± 0.27 D for SE, = 0.2042, respectively). However, significant myopic shift was observed in the atropine + SV subgroup during the quarantine time (-0.31 ± 0.39 D for SE and 0.15 ± 0.16 mm for AL, both < 0.001).
CONCLUSION
Children treated with 0.01% atropine had slower myopia progression during the lockdown period in Shanghai compared with children discontinued. Moreover, the effect of atropine on myopic prevention can be strengthened with DIMS lenses.
Topics: Humans; Child; Atropine; Retrospective Studies; China; Myopia; Refraction, Ocular
PubMed: 36778567
DOI: 10.3389/fpubh.2023.1074272 -
Medicine Jun 2024It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study,... (Observational Study)
Observational Study Randomized Controlled Trial
It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study, 172 adolescents aged 8 to 12 years who were admitted to the diopter department of Hengshui People Hospital from April 2021 to May 2022 were selected. According to the equivalent spherical diopter measured at the time of initial diagnosis, myopic patients were randomly divided into low myopia group (group A) and moderate myopia group (group B). At the same time, according to the different treatment methods, the patients were divided into the group wearing frame glasses alone (group c), the group wearing frame glasses with low-concentration Atropine (group d), the group wearing corneal shaping glasses alone at night (group e), and the group wearing corneal shaping glasses at night with low-concentration Atropine (group f). The control effect of myopia development and axial elongation in group f was better than that in groups d and e (P < .05). The effect of controlling myopia development and axial elongation in group f is with P > .05. The probability of postoperative adverse reactions in group f was lower and lower than that in the other groups. Low-concentration atropine combined with OK lens could effectively delay the development of juvenile myopia, and had a high safety. Low-concentration of Atropine would not have a significant impact on the basic tear secretion and tear film stability. Nightwear of OK lens also had no significant impact, but it would significantly reduce the tear film rupture time in the first 3 months, and at the same time, the tear film rupture time would be the same after 6 months as before treatment.
Topics: Humans; Atropine; Child; Myopia; Male; Female; Orthokeratologic Procedures; Prospective Studies; Mydriatics; Treatment Outcome; Ophthalmic Solutions; Contact Lenses
PubMed: 38875374
DOI: 10.1097/MD.0000000000038384 -
Scientific Reports Nov 2022Pesticides account for hundreds of millions of cases of acute poisoning worldwide each year, with organophosphates (OPs) being responsible for the majority of all...
Pesticides account for hundreds of millions of cases of acute poisoning worldwide each year, with organophosphates (OPs) being responsible for the majority of all pesticide-related deaths. OPs inhibit the enzyme acetylcholinesterase (AChE), which leads to impairment of the central- and peripheral nervous system. Current standard of care (SOC) alleviates acute neurologic-, cardiovascular- and respiratory symptoms and reduces short term mortality. However, survivors often demonstrate significant neurologic sequelae. This highlights the critical need for further development of adjunctive therapies with novel targets. While the inhibition of AChE is thought to be the main mechanism of injury, mitochondrial dysfunction and resulting metabolic crisis may contribute to the overall toxicity of these agents. We hypothesized that the mitochondrially targeted succinate prodrug NV354 would support mitochondrial function and reduce brain injury during acute intoxication with the OP diisopropylfluorophosphate (DFP). To this end, we developed a rat model of acute DFP intoxication and evaluated the efficacy of NV354 as adjunctive therapy to SOC treatment with atropine and pralidoxime. We demonstrate that NV354, in combination with atropine and pralidoxime therapy, significantly improved cerebral mitochondrial complex IV-linked respiration and reduced signs of brain injury in a rodent model of acute DFP exposure.
Topics: Animals; Rats; Organophosphate Poisoning; Atropine; Prodrugs; Isoflurophate; Succinic Acid; Acetylcholinesterase; Rodentia; Succinates; Mitochondria; Brain Injuries
PubMed: 36434021
DOI: 10.1038/s41598-022-24472-3 -
British Journal of Pharmacology Nov 2021The ability of the muscarinic cholinergic antagonist atropine to inhibit myopia development in humans and animal models would suggest that cholinergic hyperactivity may...
BACKGROUND AND PURPOSE
The ability of the muscarinic cholinergic antagonist atropine to inhibit myopia development in humans and animal models would suggest that cholinergic hyperactivity may underlie myopic growth. To test this, we investigated whether cholinergic agonists accelerate ocular growth rates in chickens. Furthermore, we investigated whether atropine alters ocular growth by downstream modulation of dopamine levels, a mechanism postulated to underlie its antimyopic effects.
EXPERIMENTAL APPROACH
Muscarinic (muscarine and pilocarpine), nicotinic (nicotine) and non-specific (oxotremorine and carbachol) cholinergic agonists were administered to chicks developing form-deprivation myopia (FDM) or chicks that were otherwise untreated. Vitreal levels of dopamine and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were examined using mass spectrometry MS in form-deprived chicks treated with atropine (360, 15 or 0.15 nmol). Further, we investigated whether dopamine antagonists block atropine's antimyopic effects.
KEY RESULTS
Unexpectedly, administration of each cholinergic agonist inhibited FDM but did not affect normal ocular development. Atropine only affected dopamine and DOPAC levels at its highest dose. Dopamine antagonists did not alter the antimyopia effects of atropine.
CONCLUSION AND IMPLICATIONS
Muscarinic, nicotinic and non-specific cholinergic agonists inhibited FDM development. This indicates that cholinergic hyperactivity does not underlie myopic growth and questions whether atropine inhibits myopia via cholinergic antagonism. This study also demonstrates that changes in retinal dopamine release are not required for atropine's antimyopic effects. Finally, nicotinic agonists may represent a novel and more targeted approach for the cholinergic control of myopia as they are unlikely to cause the anterior segment side effects associated with muscarinic treatment.
Topics: Animals; Atropine; Chickens; Dopamine; Humans; Muscarinic Antagonists; Myopia; Retina
PubMed: 34302355
DOI: 10.1111/bph.15629 -
The Cochrane Database of Systematic... Oct 2009Amblyopia is defined as defective visual acuity in one or both eyes without demonstrable abnormality of the visual pathway, and is not immediately resolved by wearing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Amblyopia is defined as defective visual acuity in one or both eyes without demonstrable abnormality of the visual pathway, and is not immediately resolved by wearing glasses.
OBJECTIVES
To assess the effectiveness and safety of conventional occlusion versus atropine penalization for amblyopia.
SEARCH STRATEGY
We searched CENTRAL, MEDLINE, EMBASE, LILACS, the WHO International Clinical Trials Registry Platform, preference lists, science citation index and ongoing trials up to June 2009.
SELECTION CRITERIA
We included randomized/quasi-randomized controlled trials comparing conventional occlusion to atropine penalization for amblyopia.
DATA COLLECTION AND ANALYSIS
Two authors independently screened abstracts and full text articles, abstracted data, and assessed the risk of bias.
MAIN RESULTS
Three trials with a total of 525 amblyopic eyes were included. One trial was assessed as having a low risk of bias among these three trials, and one was assessed as having a high risk of bias.Evidence from three trials suggests atropine penalization is as effective as conventional occlusion. One trial found similar improvement in vision at six and 24 months. At six months, visual acuity in the amblyopic eye improved from baseline 3.16 lines in the occlusion and 2.84 lines in the atropine group (mean difference 0.034 logMAR; 95% confidence interval (CI) 0.005 to 0.064 logMAR). At 24 months, additional improvement was seen in both groups; but there continued to be no meaningful difference (mean difference 0.01 logMAR; 95% CI -0.02 to 0.04 logMAR). The second trial reported atropine to be more effective than occlusion. At six months, visual acuity improved 1.8 lines in the patching group and 3.4 lines in the atropine penalization group, and was in favor of atropine (mean difference -0.16 logMAR; 95% CI -0.23 to -0.09 logMAR). Different occlusion modalities were used in these two trials. The third trial had inherent methodological flaws and limited inference could be drawn.No difference in ocular alignment, stereo acuity and sound eye visual acuity between occlusion and atropine penalization was found. Although both treatments were well tolerated, compliance was better in atropine. Atropine penalization costs less than conventional occlusion. The results indicate that atropine penalization is as effective as conventional occlusion.
AUTHORS' CONCLUSIONS
Both conventional occlusion and atropine penalization produce visual acuity improvement in the amblyopic eye. Atropine penalization appears to be as effective as conventional occlusion, although the magnitude of improvement differed among the three trials. Atropine penalization can be used as first line treatment for amblyopia.
Topics: Amblyopia; Atropine; Child; Child, Preschool; Humans; Occlusive Dressings; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Visual Acuity
PubMed: 19821369
DOI: 10.1002/14651858.CD006460.pub2 -
British Journal of Pharmacology Jun 1983The isolated perfused stomach of the mouse was used to study the effect of atropine and secoverine on bethanechol-induced gastric acid secretion and gastric motility....
The isolated perfused stomach of the mouse was used to study the effect of atropine and secoverine on bethanechol-induced gastric acid secretion and gastric motility. Both atropine and secoverine inhibited cholinergically induced gastric acid secretion and gastric motility. Inhibition of gastric acid secretion by atropine and secoverine occurred at a similar dose-range (10(-9) and 2 X 10(-9) M). Secoverine inhibited bethanechol-induced hypermotility at doses (10(-11) M and above) that were lower than those of atropine (2 X 10(-9) M and above) required to produce this effect. Secoverine, unlike atropine markedly inhibited gastric motility at lower doses than those which affected secretion.
Topics: Animals; Atropine; Female; Gastric Acid; Gastrointestinal Motility; In Vitro Techniques; Male; Mice; Parasympatholytics; Phenethylamines
PubMed: 6652343
DOI: 10.1111/j.1476-5381.1983.tb11027.x -
Asia-Pacific Journal of Ophthalmology... Jan 2022Myopia is now a major public health issue in parts of East and Southeast Asia, including mainland China. In this region, around 80% of students completing 12 years of... (Review)
Review
Myopia is now a major public health issue in parts of East and Southeast Asia, including mainland China. In this region, around 80% of students completing 12 years of school education are now myopic, and from 10% to 20% have high myopia in excess of -6D. Interventions to prevent the onset of myopia based on increasing time outdoors have now been implemented at a system-wide scale in Chinese Taipei (Taiwan) and Singapore with some success, but the prevalence of myopia still remains high by international standards. In mainland China, until recently, myopia prevention was largely based on eye exercises, but these have not been sufficient to prevent an epidemic. Control of myopia progression with atropine eye drops has been widely practiced in Singapore and Taiwan, with recent practice concentrating on low-dose concentrations. Orthokeratology has also been widely used across the region. Recent research has produced both contact and spectacle lenses that slow myopia progression by imposing myopic defocus. The new approaches to myopia control are ready for systematic use, which may be facilitated by system-wide screening and referral. In recent years, renewed emphasis has been placed on the prevention of myopia in mainland China by China's President Xi Jinping. In addition to making use of all the measures outlined above, China now seems to be aiming for major reforms to schooling, reducing educational pressures, particularly in the early school years, freeing more time for outdoor play and learning. These new initiatives may be crucial to myopia prevention and control.
Topics: Atropine; China; Disease Progression; Eyeglasses; Humans; Myopia; Schools
PubMed: 35044336
DOI: 10.1097/APO.0000000000000489 -
BMC Ophthalmology Jul 2016Myopia-related maculopathy is one of the leading causes of blindness in the world. The prevalence of myopia has been reported as high as 90 % in some Asian countries.... (Comparative Study)
Comparative Study
BACKGROUND
Myopia-related maculopathy is one of the leading causes of blindness in the world. The prevalence of myopia has been reported as high as 90 % in some Asian countries. Therefore, controlling myopia progression is an urgent public issue. The purpose of this study is to evaluate the effects of topical atropine with different concentrations on intraocular pressure measurements and myopia progression in school-aged children in Taiwan.
METHODS
Fifty-six myopic children were divided into three groups: 32 children were treated with 0.125 % atropine eyedrop; 12 of them were treated with 0.25 % atropine eye drop and another 12 served as a control group. IOP, auto-refractor and manifest refraction were measured at baseline and every 3 months following treatment for one year.
RESULTS
There were no significant differences for the mean age, gender and baseline IOPs among the three groups. During the follow up period, no significant IOP difference was found among three groups. The change between final and baseline mean IOPs also revealed no significant differences: 0.54 mmHg, -1.28 mmHg, -0.33 mmHg for the 0.125 % atropine, 0.25 % atropine and control groups. The baseline mean spherical equivalent similarly did not differ significantly among groups but the control group showed a significant myopic progression compared to the 0.125 % atropine group 6 months after treatment, and persisted for one year. The change between final and baseline mean spherical equivalents were -0.05 D, 0 D, -1.05 D for the 0.125 % atropine, 0.25 % atropine and control groups, with both atropine-treated groups showing significant myopic retardation compared to the control group.
CONCLUSIONS
Topical use of low concentration atropine for one year does not induce ocular hypertension and is effective for retarding myopic progression. However, further large scale studies with longer follow up period is necessary to validate the long term safety and efficacy.
TRIAL REGISTRATION
ISRCTN33002849 , 2016/01/19, retrospectively registered.
Topics: Analysis of Variance; Atropine; Case-Control Studies; Child; Disease Progression; Female; Humans; Intraocular Pressure; Male; Mydriatics; Myopia; Prospective Studies; Taiwan; Tonometry, Ocular
PubMed: 27435576
DOI: 10.1186/s12886-016-0297-y