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Assessing Paediatric Development in Psychiatry
Published in Cathy Laver-Bradbury, Margaret J.J. Thompson, Christopher Gale, Christine M. Hooper, Child and Adolescent Mental Health, 2021
The neurones that inter-connect the nuclei are either excitatory (glutaminergic) or inhibitory (GABAergic) in nature, and signals are facilitated by different neurotransmitters, as indicated in the parentheses. A third set of neurones, thought to have both excitatory and inhibitory functions, depending on circumstances, originate in the substantia nigra and utilise dopamine as a chemical messenger. It is these neurones that degrade in Parkinson’s disease and lead to the gradual onset of paucity of movement seen in these patients. L-DOPA, one of the drugs used to treat Parkinson’s, is one of the breakdown products of dopamine that is metabolically active, i.e. binds to the receptors on the postsynaptic membrane of dopaminergic synapses and so exerts the same effects as dopamine.
Propionic acidemia
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
An infant who presented with a pure hyperammonemia picture without ketoacidosis is shown in Figure 2.7. MRI of the brain revealed extensive atrophy (Figure 2.8). An unusual patient [22] was diagnosed at 31 years of age after admission to a psychiatric hospital where he was admitted for bizarre behavior and studied further because of involuntary movements. We have observed MRI evidence of hypodense myelin, along with areas of increased signal in the basal ganglia [20]. We have also encountered a metabolic stroke in an eight-year-old patient with propionic acidemia in which there was virtually complete infarction of the basal ganglia followed by death [23, 24]. We have been informed about a similar patient who did not die, but remained in a vegetative state. A 15-year-old diagnosed neonatally suddenly developed a stroke of the basal ganglia from which he ultimately recovered [25]. Assessment of cerebral vessels showed no abnormality. Treatment with L-DOPA appeared to be beneficial.
Regulation of Reproduction by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Collectively, both the origin and functions of elevated L-Dopa in different compartments of pregnancy in several species remain enigmatic and raise the following questions: (1) Is L-Dopa a critical factor for the maintenance and/or progression of successful pregnancy? (2) Does L-Dopa play an important role in fetal development or in parturition? (3) Must L-Dopa be converted to DA to exert its actions, or does it have a unique function on its own during pregnancy? Given the complexity of maternal–fetal relationship, the inability to manipulate individual pregnancy compartments, or to reduce only L-Dopa without altering the synthesis of other catecholamines, the above questions may remain unresolved for a long time.
Real-world safety and effectiveness of rotigotine in patients with Parkinson’s disease: analysis of a post-marketing surveillance study in Japan
Published in International Journal of Neuroscience, 2022
Hidefumi Ito, Tomoyo Takayama, Hiroyuki Kondo, Yasuhiko Fukuta
Throughout the follow-up period, the dosage of l-dopa remained almost unchanged (approximately 450 mg/day). The overall LED increased by approximately 160 mg/day; however, rotigotine was of low dose. This finding could have been caused by (1) low, additional doses of rotigotine causing an improvement in symptoms by, (2) the slow progression of PD [30], and there was no necessity for immediate dose increase from a risk–benefit perspective based on the physicians from their observation of the symptoms and progression status of the patients, and (3) many elderly patients in the study population, and (4) possibility of the follow-up ending during the switching of drugs. If a certain degree of improvement in symptoms was achieved by a low dose of rotigotine and improvement in the Quality of Life were achieved, a careful determination of the DA dose increases according to the patient’s condition while maintaining a uniform l-dopa dose is considered. This would reflect the actual situation in clinical practice, which would leave the door open for further dose increases in cases of disease progression.
Manganese concentration in patients with encephalopathy following ephedrone use: a narrative review and analysis of case reports
Published in Clinical Toxicology, 2022
Michal Ordak, Natalia Sloniewicz, Tadeusz Nasierowski, Elzbieta Muszynska, Magdalena Bujalska-Zadrozny
Literature data indicate that people with advanced diseases are commonly admitted to clinics. The problem is that, according to patients, these disorders appear after a few or several weeks [17,19]. It is possible that patients with milder symptoms early in the course of the disease may have lower manganese concentrations. L-DOPA preparations, as well as other anti-Parkinsonian drugs, have proved to be ineffective. Drugs that speed up the excretion of manganese from the body have been found to reduce the likelihood of disease progression but do not contribute significantly to the regression of symptoms [37,38]. Future studies should include treatment in a larger group of patients, namely comparing the efficacy of intravenous ethylenediaminetetraacetic acid (EDTA) in these patients, para-aminosalicylic acid (PAS), or supplements of iron ions to test its manganese chelating properties [39,40].
Brain insulin resistance: role in neurodegenerative disease and potential for targeting
Published in Expert Opinion on Investigational Drugs, 2020
Chronic neurodegenerative disorders such as Alzheimer’s disease (AD) or Parkinson’s disease (PD) are a major burden to the health systems. Unfortunately, no disease -modifying treatments are available that can limit or stop disease progression. Currently, the main treatment is the administration of the precursor of dopamine, L-DOPA, which offers some improvement of the symptoms to PD patients [1], but the improvement is short lived and only lasts as long as the drug is present in the system. Other treatments such as dopamine receptor agonists do not fare better. In addition, the effect of L-DOPA fades over time as the neurons in the substantia nigra that metabolize it to dopamine continue to die. Furthermore, long-term users of L-DOPA can develop serious side effects such as dyskinesia/dystonia [2]. There are only two drug types available to treat AD, both have very limited effects on the symptoms and have no disease-modifying properties. Acetylcholine esterase inhibitors can provide slight improvement of cognitive symptoms, and the NMDA glutamate receptor antagonist memantine has very limited effects on AD [3]. Hence, there is an urgent need to investigate new disease mechanisms and concepts that show promise to be more successful in the clinic.