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Clinical Neurology and Neurosurgery Jun 2024Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological... (Review)
Review
Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological diseases worldwide. PD is usually diagnosed after the third decade of life with symptoms like tremors at rest and muscle stiffness. Rapid Eye Movement sleep behavioral disorder (RBD) is another disorder that is caused by a loss of typical muscle relaxation during sleep with a lot of motor activity. Usually, RBD is strongly associated with PD. Recent studies have demonstrated that PD reduces the life expectancy of patients to 10 and 20 years after being diagnosed. In addition, delayed diagnosis and treatment of these neurological disorders have significant socio-economic impacts on patients, their partners and on the general public. Often, it is not clear about PD associated financial burdens both in low and high-income countries. On the other hand, PD triggers neurological variations that affect differences in the dopamine transporter (DAT) and in glucose metabolism. Therefore, positron emission tomography (PET) using specific DAT radiotracers and fluorine-18 labeled desoxyglucose (FDG) has being considered a key imaging technique that could be applied clinically for the very early diagnosis of RBD and in PD. However, a few myths about PET is that it is very expensive. Here, we looked at the cost of treatment of PD and RBD in relation to early PET imaging. Our finding suggests that PET imaging might also be a cost sparing diagnostic option in the management of patients with PD and RBD, not only for first world countries as it is the case now but also for the third world countries. Therefore, PET is a cost-effective imaging technique for very early diagnostic of RBD and PD.
PubMed: 38944021
DOI: 10.1016/j.clineuro.2024.108404 -
Biological Psychiatry Jun 2024Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin-sensitive...
BACKGROUND
Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin-sensitive MRI (NM-MRI) provides a marker of long-term dopamine function. We examined if midbrain NM-MRI contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia relative to controls and if this correlated with dopamine synthesis capacity.
METHODS
N=154 participants (n=74 individuals with schizophrenia and n=80 healthy controls) underwent NM-MRI of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n=38) also received [18F]-DOPA PET to measure dopamine synthesis capacity (K) in the SN-VTA and striatum.
RESULTS
SN-VTA NM-CNR was significantly higher in patients with schizophrenia relative to controls (effect size=0.38, p=0.019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA K positively correlated with SN-VTA NM-CNR (r=0.44, p=0.005) and striatal K (r=0.71, p<0.001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal K (r=0.53, p=0.005) and that this relationship appeared strongest between the ventral SN-VTA and associative striatum in schizophrenia.
CONCLUSIONS
Our results suggest that neuromelanin levels are higher in patients with schizophrenia relative to controls, particularly in midbrain regions that project to parts of the striatum which receive innervation from the limbic and association cortices. The direct relationship between measures of neuromelanin and dopamine synthesis suggests that these aspects of schizophrenia pathophysiology are linked. Our findings highlight specific mesostriatal circuits as the loci of dopamine dysfunction in schizophrenia and, thus, potential therapeutic targets.
PubMed: 38942349
DOI: 10.1016/j.biopsych.2024.06.013 -
ELife Jun 2024Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these...
Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline (NA) reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both NA and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
Topics: Animals; Dopaminergic Neurons; Serotonergic Neurons; Dorsal Raphe Nucleus; Mice; Disease Models, Animal; Oxidopamine; Parkinsonian Disorders; Male; Mice, Inbred C57BL; Desipramine; Norepinephrine
PubMed: 38940422
DOI: 10.7554/eLife.90278 -
JACC. Advances May 2024Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after...
BACKGROUND
Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known.
OBJECTIVES
This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation.
METHODS
The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m and systemic vascular resistance <800 dyne/s/cm, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed.
RESULTS
Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index.
CONCLUSIONS
Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.
PubMed: 38939630
DOI: 10.1016/j.jacadv.2024.100916 -
Acta Medica Philippina 2024Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus,...
BACKGROUND
Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted.
OBJECTIVE
Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility.
METHODS
A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures.
RESULTS
No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data.
CONCLUSION
Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility.
PubMed: 38939420
DOI: 10.47895/amp.vi0.6994 -
Cell Reports. Medicine Jun 2024In rodents with unilateral ablation of neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA induces a progressive increase of...
In rodents with unilateral ablation of neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA induces a progressive increase of behavioral responses, a process known as behavioral sensitization. This sensitization is blunted in arrestin-3 knockout mice. Using virus-mediated gene delivery to the dopamine-depleted striatum of these mice, we find that the restoration of arrestin-3 fully rescues behavioral sensitization, whereas its mutant defective in c-Jun N-terminal kinase (JNK) activation does not. A 25-residue arrestin-3-derived peptide that facilitates JNK3 activation in cells, expressed ubiquitously or selectively in direct pathway striatal neurons, also fully rescues sensitization, whereas an inactive homologous arrestin-2-derived peptide does not. Behavioral rescue is accompanied by the restoration of JNK3 activity, as reflected by JNK-dependent phosphorylation of the transcription factor c-Jun in the dopamine-depleted striatum. Thus, arrestin-3-assisted JNK3 activation in direct pathway neurons is a critical element of the molecular mechanism underlying sensitization upon dopamine depletion and chronic L-DOPA treatment.
PubMed: 38936368
DOI: 10.1016/j.xcrm.2024.101623 -
Neural Regeneration Research Jun 2024Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered...
Chitosan alleviates symptoms of Parkinson's disease by reducing acetate levels, which decreases inflammation and promotes repair of the intestinal barrier and blood-brain barrier.
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically short-chain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood-brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood-brain barriers, thereby alleviating symptoms of Parkinson's disease.
PubMed: 38934394
DOI: 10.4103/NRR.NRR-D-23-01511 -
Cureus May 2024Clozapine is an atypical antipsychotic that acts by blocking mainly dopamine 4 receptors. It is usually prescribed for treatment-resistant schizophrenia as well as...
Clozapine is an atypical antipsychotic that acts by blocking mainly dopamine 4 receptors. It is usually prescribed for treatment-resistant schizophrenia as well as treatment-resistant bipolar disorder. Clozapine has a wide profile of side effects that result from blocking different receptors all over the body. A 42-year-old Middle Eastern female is known to have suffered from schizoaffective disorder for many years and had frequent relapses despite compliance with treatment. She was commenced on Clozapine; the patient started complaining of an electric shock sensation throughout her body that resulted in recurrent falls with bilateral leg fractures. She was started on sodium valproate to exclude the possibility of seizure activity but the electric shock sensation did not subside. The decision was made to switch her to aripiprazole and gradually taper down and stop Clozapine which improved her symptoms. Careful monitoring of patients who receive Clozapine is recommended especially during the tapering phase due to the risky adverse events it can bring about. It is essential to understand the side effects in order to tackle them as soon as they arise.
PubMed: 38933635
DOI: 10.7759/cureus.61143 -
Cureus May 2024Lesch-Nyhan syndrome (LNS) is a disease characterized by a reduced ability to recycle purines, leading to increased de novo purine synthesis and uric acid production....
Lesch-Nyhan syndrome (LNS) is a disease characterized by a reduced ability to recycle purines, leading to increased de novo purine synthesis and uric acid production. Patients classically present with an array of hyperuricemic, neurologic, and behavioral symptoms. In this report, we describe a 26-year-old male with a history of LNS and recurrent fevers of unknown origin who presented to the emergency department (ED) with a fever, hypotension, and hypernatremia. We suspect that our patient's presentation was caused by autonomic instability in the setting of LNS leading to excessive free water loss. This report highlights a rare but life-threatening manifestation of LNS.
PubMed: 38933625
DOI: 10.7759/cureus.61170 -
Polymers Jun 2024Biofouling is a great challenge for engineering material in medical-, marine-, and pharmaceutical-related applications. In this study, a novel trimethylamine -oxide...
Biofouling is a great challenge for engineering material in medical-, marine-, and pharmaceutical-related applications. In this study, a novel trimethylamine -oxide (TMAO)-analog monomer, 3-(2-methylacrylamido)-,-dimethylpropylamine -oxide (MADMPAO), was synthesized and applied for the grafting of poly(MADMPAO) (MPAO) brushes on quartz crystal microbalance (QCM) chips by the combination of bio-inspired poly-dopamine (DA) and surface-initiated atom transfer radical polymerization technology. The result of ion adsorption exhibited that a sequential DA and MPAO arrangement from the chip surface had different characteristics from a simple DA layer. Ion adsorption on MPAO-grafted chips was greatly inhibited at low salt concentrations of 1 and 10 mmol/L due to strong surface hydration in the presence of charged N and O of zwitterionic MPAO brushes on the outer layer on the chip surface, well known as the "anti-polyelectrolyte" effect. During BSA adsorption, MPAO grafting also led to a marked decrease in frequency shift, indicating great inhibition of protein adsorption. It was attributed to weaker BSA-MPAO interaction. In this study, the Au@DA-4-MPAO chip with the highest coating concentration of DA kept stable dissipation in BSA adsorption, signifying that the chip had a good antifouling property. The research provided a novel monomer for zwitterionic polymer and demonstrated the potential of MPAO brushes in the development and modification of antifouling materials.
PubMed: 38931984
DOI: 10.3390/polym16121634