Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.
Background and Purpose-There is evidence and international consensus on the advantages and potential of a polypill for established cardiovascular disease patients to improve adherence in the secondary prevention of cardiovascular disease. This study aimed to estimate the numbers of stroke patients who would be eligible for the polypill strategy in China, and the suitable composition of a polypill, based on data of the China National Stroke Prevention Project. Methods-A total of 717 620 residents aged ≥40 years from 6 Chinese representative provinces were screened for prevalent stroke from 2011 to 2012 with an 84.4% response rate. Participants with a history of stroke received further investigation of risk factors and treatments. The potential need for treatment was classified according to the guidelines. Rates were standardized using the population composition of the Sixth National Population Census of China. Results-The standardized prevalence rate of stroke was 1.9%. Up to 93.1% of stroke patients were eligible for a polypill containing at least 2 types of medications, with 75.3% eligible for a statin and antiplatelet agent and 70.6% for antihypertensive and antiplatelet medications. Considering 3 therapies, 54% were eligible for antihypertensive, statin, and antiplatelet medications. The current treatment rate with all required combinations of separate pills was only 6.9%. Conclusions-A huge number of stroke patients in China require preventive therapy and would be eligible for a polypill.This study indicates that it would be reasonable to consider and assess the value of a polypill strategy to improve secondary prevention of stroke in China.
BackgroundIntracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole‐brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke.Methods and ResultsSixty‐one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole‐brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque‐wall contrast ratio, high signal on T1‐weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole‐brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1‐weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9–44.1; P=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8–164.9; P=0.013), and type 2 (≥50% cross‐sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3–82.2; P=0.030) were independently associated with culprit lesions.ConclusionsHigh signal on T1‐weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.
ObjectiveTo investigate whether elevated plasma trimethylamine N-oxide (TMAO) levels are associated with initial stroke severity and infarct volume.MethodsThis cross-sectional study included 377 patients with acute ischemic stroke and 50 healthy controls. Plasma TMAO levels were assessed at admission. Stroke infarct size and clinical stroke severity were measured with diffusion-weighted imaging and the NIH Stroke Scale (NIHSS). Mild stroke was defined as an NIHSS score <6.ResultsPlasma TMAO levels were higher in patients with ischemic stroke than in healthy controls (median 5.1 vs 3.0 μmol/L; p < 0.001). Every 1–µmol/L increase in TMAO was associated with a 1.13-point increase in NIHSS score (95% confidence interval [CI] 1.04–1.29; p < 0.001) and 1.69-mL increase in infarct volume (95% CI 1.41–2.03; p < 0.001) after adjustment for vascular risk factors. At admission, 159 patients (42.2%) had experienced a mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke (median 3.6 vs 6.5 µmol/L; p < 0.001). The area under the receiver operating characteristics curve of plasma TMAO level in predicting moderate to severe stroke was 0.794 (95% CI 0.748–0.839; p < 0.001), and the optimal cutoff value was 4.95 μmol/L. The sensitivity and specificity of TMAO levels ≥4.95 μmol/L for moderate to severe stroke were 70.2% and 79.9%, respectively.ConclusionsPatients with ischemic stroke had higher plasma TMAO levels compared to healthy controls. Higher plasma TMAO level at admission is an independent predictor of stroke severity and infarct volume in patients with acute ischemia.
Internal jugular vein stenosis (IJVS), characterized by a series of clinical manifestations, such as head and neck symptoms, visual and ear symptoms, as well as sleep disorder, has been receiving attention in recent years. However, its’ etiologies are not fully understood.
We report a cases series of IJVS induced by styloid oppression. We define it as the stylo-jugular type of Eagle syndrome (ES).
Our study reveals that external oppression, especially by styloid process, is an important etiology of IJVS. The stylo-jugular ES diagnosis can be identified by Computed tomography venography. Whether stylo-jugular ES can be corrected by styloidectomy requires further investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.