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Neuroendocrine tumours
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Sairah R Khan, Kathryn L Wallitt, Adil Al-Nahhas, Tara D Barwick
Dihydroxyphenylalanine (DOPA) is a neutral amino acid that resembles natural L-dopa and can be labelled with fluorine-18 (18F) for PET imaging. It was originally used in patients with Parkinson's disease to assess the integrity of the striatal dopaminergic system, but has more recently been shown to contribute to imaging NETs because of increased activity of L-DOPA decarboxylase. However, the role of 18F-DOPA has not been achieved completely because of associated difficulties in synthesis and availability. In addition, the intense physiological uptake in the pancreas and adrenals poses serious problems in identifying pancreatic lesions with certainty (37).
Biogenic amines
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
Treatment of the central deficiency of dopamine with L-DOPA has been the treatment of choice, and virtually always with carbidopa [25, 29, 34]. The most readily available preparations contain carbidopa or benserazide. Therapeutically successful doses of DOPA employed have been 3–10 mg/kg per day, but it is advisable to start with 0.1–0.5–1 mg/kg divided into three or four doses, and to increase weekly. Hypersensitivity to DOPA has been especially observed in type B patients; some tolerated only 0.5 mg/kg and some none. Inhibitors of dopamine degradation, such as selegiline, have been employed (see Table 17.2). Patients who tolerate a reasonable dose of L-DOPA generally displayed a good or moderately good response. Improvement in movement, hypokinesis, tremor, rigidity, and dystonia are often dramatic, permitting impressive improvement up to completely normal motor function in some. Children who had been wheelchair-bound for years have walked [29]. Clinical improvement is lasting, and patients have been followed over decades. Most patients have not had CSF levels of HVA monitored, but improvement clinically was found, even despite a failure to return CSF HVA to normal.
Involvement of Dopamine with Various Cancers
Published in Nira Ben-Jonathan, Dopamine, 2020
Immunoreactive D2R was evaluated in NET samples from 44 patients [116]. D2R was positive in 85% of the samples (100% of bronchial carcinoids and 93% of islet cell tumors), and its intensity in NETs was similar to that of pituitary samples. No differences in D2R expression were seen with respect to tumor grading, size, proliferative activity, presence of metastases, endocrine activity, or gender. However, D2R expression was significantly higher in the more aggressive tumors than in those without recurrence/progression of disease. The authors concluded that the high expression of D2R in NETs is clinically significant and that the ability of DA drugs to suppress NETs should be exploited. The unique secretory characteristics of NETs lend themselves to imaging by positron emission tomography (PET), which can target specific metabolic pathways or receptors [117,118]. Among these, C-11- or F-18-Dopa (Dopa PET), and radiolabeled DA analogs such as fluorine 18 (F18-DA), have been used to identify neuroendocrine GI tumors [119].
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.
The potential role of 2D-speckle tracking echocardiography for detecting left ventricular systolic dysfunction in patients with Parkinson’s disease: a case control study
Published in Acta Cardiologica, 2021
Mostafa Osama El Mokadem, Amr Hassan, Mona Hussein, Yousef Mohsen Mohamed
In our study 92.5% of PD patients were treated with L-dopa. 28 PD patients were treated with dopamine agonists (Pramipexole). There are multiple mechanisms that may explain the occurrence of myocardial dysfunction in patients with PD. One of these mechanisms is that Levodopa (L-dopa), the mainline of therapy in PD, was found to increase serum homocysteine levels [17]. Homocysteine is a well-known risk factor for cardiovascular disease [18]. This makes PD patients at increased risk of atherosclerosis and ischaemic heart disease. However, this assumption is not convincing in presence of homogenous peaks of regional systolic strain in addition to bull’s-eye analysis being not consistent with specific coronary artery territory. Our speculations were in agreement with Günaydın et al. They conducted a study to assess the effect of treatment with L-dopa on left ventricular global systolic function using speckle tracking technique compared with the control group. They found similar values of EF and GLS in both groups [19].
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.