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Genes Mar 2022Parkinson's disease (PD) is a disorder characterized by a triad of motor symptoms (akinesia, rigidity, resting tremor) related to loss of dopaminergic neurons mainly in... (Review)
Review
Parkinson's disease (PD) is a disorder characterized by a triad of motor symptoms (akinesia, rigidity, resting tremor) related to loss of dopaminergic neurons mainly in the . Diagnosis is often made after a substantial loss of neurons has already occurred, and while dopamine replacement therapies improve symptoms, they do not modify the course of the disease. Although some biological mechanisms involved in the disease have been identified, such as oxidative stress and accumulation of misfolded proteins, they do not explain entirely PD pathophysiology, and a need for a better understanding remains. Neurodegenerative diseases, including PD, appear to be the result of complex interactions between genetic and environmental factors. The latter can alter gene expression by causing epigenetic changes, such as DNA methylation, post-translational modification of histones and non-coding RNAs. Regulation of genes responsible for monogenic forms of PD may be involved in sporadic PD. This review will focus on the epigenetic mechanisms regulating their expression, since these are the genes for which we currently have the most information available. Despite technical challenges, epigenetic epidemiology offers new insights on revealing altered biological pathways and identifying predictive biomarkers for the onset and progression of PD.
Topics: Dopamine; Dopaminergic Neurons; Epigenesis, Genetic; Epigenomics; Humans; Parkinson Disease
PubMed: 35328033
DOI: 10.3390/genes13030479 -
Canadian Medical Association Journal Dec 1969The last 10 years have seen great activity in the investigation of cerebral catecholamines, particular attention having been paid to dopamine. The low dopamine content... (Review)
Review
The last 10 years have seen great activity in the investigation of cerebral catecholamines, particular attention having been paid to dopamine. The low dopamine content in the basal ganglia and in the urine of patients with Parkinson's disease led to the logical use of the precursor DOPA in the treatment of this disorder. Between 1961 and 1966, both the oral and the intravenous routes were utilized and some effects were noted upon akinesia and rigidity. The doses then used were low and the results remained somewhat controversial. When higher oral levels of L-dopa were introduced, the beneficial action of L-dopa upon parkinsonian symptoms and signs was proved beyond doubt, but there came to light a number of troublesome side effects, the worst of which were hypotension and a variety of abnormal involuntary movements. Recently, new approaches to the therapy have been tried and the sum total of these observations is to challenge our peace of mind regarding a seemingly logical chain of events. We are convinced that such second thoughts will eventually result in better and safer methods of treating this too frequent and disabling neurological disorder.
Topics: Dihydroxyphenylalanine; Dopamine; Humans; Parkinson Disease
PubMed: 4903690
DOI: No ID Found -
Cureus Mar 2023Although Takotsubo syndrome (TS) has been long recognized, it is now more frequently identified as a cause of stress-induced cardiac injury since its first description...
Although Takotsubo syndrome (TS) has been long recognized, it is now more frequently identified as a cause of stress-induced cardiac injury since its first description in the 1990s. While most cases are transient, many patients can have acute and long-term effects including persistent or worsening heart failure, arrhythmia, cardiac thrombi, outflow tract obstruction, ventricular wall rupture, and cardiogenic shock. Medical optimization is necessary to prevent cardiac remodeling and disease recurrence and manage associated heart failure. The choice of medications may vary from patient to patient based on the inciting factor or the most probable cause. Anticoagulation can be added for a small period of time if there is a concern for thrombus formation from akinesia/dyskinesia. Most patients achieve early recovery and resolution of symptoms and those with persistent manifestations can be managed medically.
PubMed: 37056535
DOI: 10.7759/cureus.36056 -
Animals : An Open Access Journal From... Jan 2023The aims of the study included evaluating the effects of levobupivacaine combined with cisatracurium on akinesia and mydriasis when administered by peribulbar injection,...
The aims of the study included evaluating the effects of levobupivacaine combined with cisatracurium on akinesia and mydriasis when administered by peribulbar injection, and evaluating if the chosen dose of cisatracurium is enough to avoid the use of systemic neuromuscular blockade in cats. The animals were divided into four groups as follows: group L received 1.25 mg kg levobupivacaine administered by peribulbar injection; group LC received the same dose of levobupivacaine combined with 0.01 mg kg of cisatracurium administered by peribulbar injection; group C received 0.01 mg kg of cisatracurium administered by peribulbar injection; group GC received 0.01 mg kg of cisatracurium intravenously. Physiological variables, intraocular pressure, akinesia, and mydriasis were measured before and up to 30 min after peribulbar injection. The onset of akinesia, duration of akinesia, and train of four (TOF) were evaluated. Physiological variables remained in the physiological range in all groups. Effective akinesia and mydriasis were observed in all groups. The (TOF) was 0.9 in all groups. Throughout the study was observed in group LC a shortened onset of akinesia and a prolonging its duration. The peribulbar injection of cisatracurium and levobupivacaine provided effective akinesia and mydriasis, and shortened the onset of akinesia while prolonging its duration.
PubMed: 36611778
DOI: 10.3390/ani13010170 -
Saudi Journal of Anaesthesia Oct 2014Neurosurgery in awake patients incorporates newer technologies that require the anesthesiologists to update their skills and evolve their methodologies. They need... (Review)
Review
Neurosurgery in awake patients incorporates newer technologies that require the anesthesiologists to update their skills and evolve their methodologies. They need effective communication skills and knowledge of selecting the right anesthetic drugs to ensure adequate analgesia, akinesia, along with patient satisfaction with the anesthetic conduct throughout the procedure. The challenge of providing adequate anesthetic care to an awake patient for intracranial surgery requires more than routine vigilance about anesthetic management.
PubMed: 25422613
DOI: 10.4103/1658-354X.140890 -
Revista Portuguesa de Cardiologia :... Sep 2012Takotsubo cardiomyopathy is a reversible condition, characterized by transient left ventricular systolic dysfunction, that mimics an acute coronary syndrome. It usually... (Review)
Review
Takotsubo cardiomyopathy is a reversible condition, characterized by transient left ventricular systolic dysfunction, that mimics an acute coronary syndrome. It usually occurs after physical or emotional stress, predominantly in postmenopausal women, although it also can affect younger age groups and males. It often presents as chest pain or dyspnea with electrocardiographic changes and mild elevation of cardiac enzymes suggesting acute myocardial infarction. Coronary angiography excludes obstructive coronary disease, and imaging reveals ventricular apical akinesia and compensatory hypercontractility of the basal segments. Various pathophysiological mechanisms have been proposed for the syndrome, such as occult atherosclerotic disease, multivessel spasm and/or microvascular dysfunction. However, the most widely accepted hypothesis at present is an excess of catecholamines causing calcium overload in cardiac myocytes, leading to disruption of contraction and ventricular function. Treatment is essentially supportive, with spontaneous and complete reversal of the changes within days or weeks. However, the presence of complications and comorbidities may predict a more adverse prognosis. As much is still unknown about takotsubo cardiomyopathy and the number of reported cases is growing, we present a literature review.
Topics: Female; Humans; Male; Prognosis; Takotsubo Cardiomyopathy
PubMed: 22795894
DOI: 10.1016/j.repc.2012.02.014 -
International Journal of Molecular... Oct 2022Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be...
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is considered the gold-standard treatment for PD; however, underlying therapeutic mechanisms need to be comprehensively elucidated, especially in relation to glial cells. We aimed to understand the effects of STN-microlesions and STN-DBS on striatal glial cells, inflammation, and extracellular glutamate/GABAergic concentration in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Rats with unilateral striatal 6-OHDA and electrodes implanted in the STN were divided into two groups: DBS OFF and DBS ON (5 days/2 h/day). Saline and 6-OHDA animals were used as control. Akinesia, striatal reactivity for astrocytes, microglia, and inflammasome, and expression of cytokines, cell signaling, and excitatory amino acid transporter (EAAT)-2 were examined. Moreover, striatal microdialysis was performed to evaluate glutamate and GABA concentrations. The PD rat model exhibited akinesia, increased inflammation, glutamate release, and decreased glutamatergic clearance in the striatum. STN-DBS (DBS ON) completely abolished akinesia. Both STN-microlesion and STN-DBS decreased striatal cytokine expression and the relative concentration of extracellular glutamate. However, STN-DBS inhibited morphological changes in astrocytes, decreased inflammasome reactivity, and increased EAAT2 expression in the striatum. Collectively, these findings suggest that the beneficial effects of DBS are mediated by a combination of stimulation and local microlesions, both involving the inhibition of glial cell activation, neuroinflammation, and glutamate excitotoxicity.
Topics: Animals; Rats; Parkinson Disease; Oxidopamine; Deep Brain Stimulation; Inflammasomes; Electrodes; Glutamates; Inflammation; Cytokines; Amino Acid Transport Systems; gamma-Aminobutyric Acid
PubMed: 36292973
DOI: 10.3390/ijms232012116 -
Journal of Neural Transmission (Vienna,... Jun 2022A time span of 60 years covers the detection of catecholamines in the brain, their function in movement and correlation to Parkinson's disease (PD). The clinical... (Review)
Review
A time span of 60 years covers the detection of catecholamines in the brain, their function in movement and correlation to Parkinson's disease (PD). The clinical findings that orally given L-DOPA can alleviate or even prevent akinesia gave great hope for the treatment of PD. Attention focused on the role of tyrosine hydroxylase (TH) as the rate-limiting enzyme in the formation of catecholamines. It became evident that the enzyme driven formation is lowered in PD. Such results could only be obtained from studying human brain samples demonstrating the necessity for human brain banks. Originally, a TH enzyme deficiency was suspected in PD. Studies were conducted on the enzyme properties: its induction and turnover, the complex regulation starting with cofactor requirements as tetrahydrobiopterin and ferrous iron, and the necessity for phosphorylation for activity as well as inhibition by toxins or regulatory feedback inhibition by catecholamines. In the course of time, it became evident that neurodegeneration and cell death of dopaminergic neurons is the actual pathological process and the decrease of TH a cophenomenon. Nevertheless, TH immunochemistry has ever since been a valuable tool to study neuronal pathways, neurodegeneration in various animal models of neurotoxicity and cell cultures, which have been used as well to test potential neuroprotective strategies.
Topics: Animals; Catecholamines; Dopaminergic Neurons; Levodopa; Parkinson Disease; Tyrosine 3-Monooxygenase
PubMed: 35460433
DOI: 10.1007/s00702-022-02488-3 -
Frontiers in Human Neuroscience 2022Freezing of gait (FOG) is a common symptom in the late stages of Parkinson's disease and related disorders. Videos are the gold standard method to conduct FOG scoring;...
Freezing of gait (FOG) is a common symptom in the late stages of Parkinson's disease and related disorders. Videos are the gold standard method to conduct FOG scoring; however, the measurement accuracy of FOG scoring based on videos has not been formally assessed, despite its use in previous studies. This study aimed to calculate the measurement accuracy of video-based FOG scoring. Three evaluators scored the FOG based on 157 video data points collected from 21 patients using an annotation tool. One evaluator measured the intra-rater reliability of the retest. The total duration of observed FOG, percentage of the time spent with FOG during the walking task (%FOG), and FOG phenotypes (shuffling, trembling, and complete akinesia) were evaluated. Intraclass correlation coefficients were used to determine the intra- and inter-rater reliabilities. The duration of FOG and %FOG showed good measurement accuracy for both intra-rater and inter-rater reliabilities. However, the FOG phenotypes showed poor measurement accuracy in inter-rater reliability. These results indicate that the temporal characteristics of FOG can be scored with a high degree of measurement accuracy, even with different evaluators; conversely, the FOG phenotypes need to be scored by several evaluators.
PubMed: 35664344
DOI: 10.3389/fnhum.2022.828355 -
Fetal Diagnosis and Therapy 2021The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have...
INTRODUCTION
The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS).
METHODS
The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form.
RESULTS
An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies.
DISCUSSION/CONCLUSION
The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams.
Topics: Arthrogryposis; Contracture; Critical Pathways; Female; Fetus; Humans; Pregnancy
PubMed: 34775380
DOI: 10.1159/000520869