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International Journal of Molecular... Aug 2023Glutamine (Gln), glutamate (Glu), and γ-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocyte-derived Gln is the precursor...
Glutamine (Gln), glutamate (Glu), and γ-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocyte-derived Gln is the precursor for the two most important neurotransmitters in the central nervous system (CNS), which are the excitatory neurotransmitter Glu and the inhibitory neurotransmitter GABA. In addition to their roles in neurotransmission, these amino acids can be used as alternative substrates in brain metabolism that enable metabolic coupling between astrocytes and neurons in the glutamate-glutamine cycle (GGC). The disturbed homeostasis of these amino acids within the tripartite synapse may be involved in the pathogenesis of various neurological diseases. Interactions between astrocytes and neurons in terms of Gln, Glu, and GABA homeostasis were studied in different phases of experimental allergic encephalomyelitis (EAE) in Lewis rats. The results of the study showed a decrease in the transport (uptake and release) of Gln and GABA in both neuronal and astrocyte-derived fractions. These effects were fully or partially reversed when the EAE rats were treated with memantine, a NMDA receptor antagonist. Changes in the expression and activity of selected glutamine/glutamate metabolizing enzymes, such as glutamine synthase (GS) and phosphate-activated glutaminase (PAG), which were affected by memantine, were observed in different phases of EAE. The results suggested perturbed homeostasis of Gln, Glu, and GABA during EAE, which may indicate alterations in neuron-astrocyte coupling and dysfunction of the tripartite synapse. Memantine appears to partially regulate the disturbed relationships between Gln, Glu, and GABA.
Topics: Animals; Rats; Rats, Inbred Lew; Encephalomyelitis, Autoimmune, Experimental; Glutamine; Memantine; Brain; Glutamic Acid; gamma-Aminobutyric Acid; Amino Acids; Homeostasis; Antifibrinolytic Agents
PubMed: 37685956
DOI: 10.3390/ijms241713149 -
Cureus Aug 2023In this report, we present a case series involving four pediatric patients who sustained a traumatic brain injury (TBI) and required intensive care unit admission...
In this report, we present a case series involving four pediatric patients who sustained a traumatic brain injury (TBI) and required intensive care unit admission immediately after the injury. In each of the four cases, amantadine was started during the acute care hospital admission to address agitation. Cases were retrieved from the electronic medical record at the Children's Hospital of Philadelphia between July 1, 2020, and October 31, 2022. This case series describes clinical data on TBI presentation, amantadine administration, patient behavior, and hospital course relating to agitation. This is the first publication that reports the effect of amantadine on agitation in the acute phase of recovery in the pediatric TBI population. Improvement in agitation was observed within 48 hours of amantadine initiation in all four cases based on the primary team progress notes, as well as the quantity of pro re nata medications given for agitation. Resolution of agitation was also observed in all cases, though the time scale varied. No adverse events were reported in relation to amantadine use, supporting other reports that the medication may be well tolerated in the pediatric population. More research is needed to determine the optimal dose of amantadine for the pediatric population and whether amantadine hastens agitation resolution compared to the current standard of care.
PubMed: 37664300
DOI: 10.7759/cureus.42892 -
World Journal of Clinical Cases Nov 2023Tardive dyskinesia (TD) is a serious and disabling movement disorder; it impairs social function and quality of life and increases the mortality rate. TD is usually...
BACKGROUND
Tardive dyskinesia (TD) is a serious and disabling movement disorder; it impairs social function and quality of life and increases the mortality rate. TD is usually induced by the use of antipsychotic drugs; however, the underlying mechanism remains unclear. Pharmacotherapy of TD includes cholinergic drugs, benzodiazepines, ginkgo biloba extract (GBE), antioxidants, amantadine, propanolol, botulinum toxin, valbenazine, and deutetrabenazine, whereas the non-pharmacotherapy approach includes modified electroconvulsive therapy (MECT) and deep brain stimulation. We successfully treated a chronic schizophrenia patient with comorbid long-term severe TD using deutetrabenazine, clozapine, and MECT.
CASE SUMMARY
A 69-year-old woman who was diagnosed as having schizophrenia 16 years ago developed severe TD after 6-mo prescription of risperidone oral solution. Her TD symptoms did not resolve despite various treatments, such as GBE, vitamin E, trihexyphenidyl, promethazine, benzodiazepines, and switching to quetiapine and olanzapine. After admission, she was given deutetrabenazine 6 mg bid. Her buccal tremor was slightly resolved 3 d later; however, her tongue remained protruded and could not be retracted. Quetiapine was switched to clozapine on day 4, and the buccal tremor remarkably resolved, and the tongue could be retracted into the mouth from day 6 onward. After three sessions of MECT, the buccal tremor resolved further. Since then, she has been able to take a semifluid diet, and her quality of life improved remarkably during 6 mo of follow-up.
CONCLUSION
TD is a serious condition which could be caused by antipsychotic medications; however, the best strategy against TD is prevention and monitoring during using antipsychotics. For patients with TD caused by antipsychotic medication use, multiple measures should be considered like switching to clozapine, adjunction with deutetrabenazine, or even MECT.
PubMed: 38073685
DOI: 10.12998/wjcc.v11.i32.7895 -
The Science of the Total Environment Jul 2024The presence of contaminants of emerging concern in aquatic ecosystems represents an ever-increasing environmental problem. Aquatic biota is exposed to these...
The presence of contaminants of emerging concern in aquatic ecosystems represents an ever-increasing environmental problem. Aquatic biota is exposed to these contaminants, which can be absorbed and distributed to their organs. This study focused on the assessment, distribution, and ecological risk of 32 CECs in a Spanish river impacted by effluents from a wastewater treatment plant, analyzing the organs and plasma of common carp. Environmental concentrations in water and sediment were examined at sites upstream and downstream of the wastewater treatment plant. The two downstream sites showed 15 times higher total concentrations (12.4 μg L and 30.1 μg L) than the two upstream sites (2.08 μg L and 1.66 μg L). Half of the CECs were detected in fish organs, with amantadine having the highest concentrations in the kidney (158 ng g w.w.) and liver (93 ng g w.w.), followed by terbutryn, diazepam, and bisphenol F in the brain (50.2, 3.82 and 1.18 ng g w.w.). The experimental bioaccumulation factors per organ were compared with the bioconcentration factors predicted by a physiologically based pharmacokinetic model, obtaining differences of one to two logarithmic units for most compounds. Risk quotients indicated a low risk for 38 % of the contaminants. However, caffeine and terbutryn showed an elevated risk for fish. The mixed risk quotient revealed a medium risk for most of the samples in the three environmental compartments: surface water, sediment, and fish.
Topics: Water Pollutants, Chemical; Wastewater; Animals; Environmental Monitoring; Geologic Sediments; Risk Assessment; Carps; Rivers; Spain; Fishes
PubMed: 38768727
DOI: 10.1016/j.scitotenv.2024.173358 -
Brain Sciences Nov 2023Mitochondrial dysfunction is well-established in Parkinson's disease (PD); however, its dysfunctions associating with cell organelle connectivity remain unknown. We...
Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson's Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity.
Mitochondrial dysfunction is well-established in Parkinson's disease (PD); however, its dysfunctions associating with cell organelle connectivity remain unknown. We aimed to establish the crucial cytosolic protein involved in organelle connectivity between mitochondria and the endopalmic reticulum (ER) through a computational approach by constructing an organelle protein network to extract functional clusters presenting the crucial PD protein connecting organelles. Then, we assessed the influence of anti-parkinsonism drugs ( = 35) on the crucial protein through molecular docking and molecular dynamic simulation and further validated its gene expression in PD participants under, istradefylline ( = 25) and amantadine ( = 25) treatment. Based on our investigation, D-aspartate oxidase (DDO )protein was found to be the critical that connects both mitochondria and the ER. Further, molecular docking showed that istradefylline has a high affinity (-9.073 kcal/mol) against DDO protein, which may disrupt mitochondrial-ER connectivity. While amantadine (-4.53 kcal/mol) shows negligible effects against DDO that contribute to conformational changes in drug binding, Successively, DDO gene expression was downregulated in istradefylline-treated PD participants, which elucidated the likelihood of an istradefylline off-target mechanism. Overall, our findings illuminate the off-target effects of anti-parkinsonism medications on DDO protein, enabling the recommendation of off-target-free PD treatments.
PubMed: 38002511
DOI: 10.3390/brainsci13111551 -
Tremor and Other Hyperkinetic Movements... 2024Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval,...
BACKGROUND
Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus.
METHODS
Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies.
RESULTS
The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus.
CONCLUSION
Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.
Topics: Humans; Male; Amantadine; Multiple System Atrophy; Ocular Motility Disorders; Aged
PubMed: 38737300
DOI: 10.5334/tohm.832 -
Scientific Reports Apr 2024Using deep learning has demonstrated significant potential in making informed decisions based on clinical evidence. In this study, we deal with optimizing medication and...
Using deep learning has demonstrated significant potential in making informed decisions based on clinical evidence. In this study, we deal with optimizing medication and quantitatively present the role of deep learning in predicting the medication dosage for patients with Parkinson's disease (PD). The proposed method is based on recurrent neural networks (RNNs) and tries to predict the dosage of five critical medication types for PD, including levodopa, dopamine agonists, monoamine oxidase-B inhibitors, catechol-O-methyltransferase inhibitors, and amantadine. Recurrent neural networks have memory blocks that retain crucial information from previous patient visits. This feature is helpful for patients with PD, as the neurologist can refer to the patient's previous state and the prescribed medication to make informed decisions. We employed data from the Parkinson's Progression Markers Initiative. The dataset included information on the Unified Parkinson's Disease Rating Scale, Activities of Daily Living, Hoehn and Yahr scale, demographic details, and medication use logs for each patient. We evaluated several models, such as multi-layer perceptron (MLP), Simple-RNN, long short-term memory (LSTM), and gated recurrent units (GRU). Our analysis found that recurrent neural networks (LSTM and GRU) performed the best. More specifically, when using LSTM, we were able to predict levodopa and dopamine agonist dosage with a mean squared error of 0.009 and 0.003, mean absolute error of 0.062 and 0.030, root mean square error of 0.099 and 0.053, and R-squared of 0.514 and 0.711, respectively.
Topics: Humans; Parkinson Disease; Levodopa; Catechol O-Methyltransferase; Activities of Daily Living; Dopamine Agonists; Neural Networks, Computer
PubMed: 38600209
DOI: 10.1038/s41598-024-59179-0 -
Qatar Medical Journal 2023Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of...
BACKGROUND
Parkinsonism-hyperpyrexia syndrome (PHS) is a potentially life-threatening condition that occurs due to the abrupt withdrawal or significant dose reduction of antiparkinsonian medications. It presents similarly to neuroleptic malignant syndrome (NMS) and is characterized by severe rigidity, fever, autonomic instability, and altered mental status.
CASE
A 62-year-old male with a 10-year history of Parkinson's disease (PD) underwent laparoscopic mesh repair for a left-sided diaphragmatic and large hiatus hernia. His antiparkinsonian medications included levodopa/carbidopa, amantadine, pramipexole, and benzhexol. Medications were withheld as part of the nil per os (NPO) status. Postoperatively, he developed withdrawal features, including tremors, difficulty speaking, tachycardia, hypertension, fever, and sweating. PHS, resulting from the withdrawal of antiparkinsonian medications, was diagnosed. The patient was transferred to the intensive care unit (ICU), intubated, and his antiparkinsonian medications were reintroduced. The patient's condition improved gradually, and he was discharged home on the 15th postoperative day.
DISCUSSION
The abrupt discontinuation of antiparkinsonian medications precipitated PHS in our patient. Recognizing the clinical picture of PHS and differentiating it from other possible conditions, such as neuroleptic malignant syndrome and malignant hyperthermia, is pivotal. Management involves resuming medications and providing supportive care. Early recognition and prompt reintroduction of the antiparkinsonian medications are essential for the patient's recovery.
CONCLUSION
PHS is a rare but potentially life-threatening condition that occurs due to the withdrawal of antiparkinsonian medications, leading to an acute hypodopaminergic state. Our case emphasizes the importance of careful perioperative management of antiparkinsonian medications and early recognition and management of withdrawal symptoms in patients with Parkinson's disease undergoing surgery.
PubMed: 38204562
DOI: 10.5339/qmj.2023.34 -
Food Chemistry: X Jun 2024The presence of veterinary drug residues in aquatic products represents a significant challenge to food safety. The current detection methods, limited in both scope and...
The presence of veterinary drug residues in aquatic products represents a significant challenge to food safety. The current detection methods, limited in both scope and sensitivity, underscore the urgent need for more advanced techniques. This research introduces a swift and potent screening technique using high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and a refined QuEChERS protocol, allowing simultaneous qualitative and semi-quantitative analysis of 192 residues. A comprehensive database, employing full scan mode and data-dependent secondary mass spectroscopy, enhances screening accuracy. The method involves efficient extraction using 90% acetonitrile, dehydration with NaSO, and acetic acid, followed by cleanup using dispersive solid-phase extract sorbent primary secondary amine. It is suitable for samples with varying fat content, offering detection limits ranging from 0.5 to 10 μg/kg, high recovery rates (60-120%), and low relative standard deviations (<20%). Practical application has validated its effectiveness for multi-residue screening, marking a significant advancement in food safety evaluation.
PubMed: 38855097
DOI: 10.1016/j.fochx.2024.101504 -
Research Square Sep 2023Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic...
Prediction of Adverse Events Risk in Patients with Comorbid Post- Traumatic Stress Disorder and Alcohol Use Disorder Using Electronic Medical Records by Deep Learning Models.
BACKGROUND
Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients.
METHODS
We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death).
RESULTS
DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk.
CONCLUSIONS
DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.
PubMed: 37790550
DOI: 10.21203/rs.3.rs-3299369/v1