Jinse Park

Coenzyme Q10 restores amyloid beta-inhibited proliferation of neural stem cells by activating the PI3K pathway.

Neurogenesis in the adult brain is important for memory and learning, and the alterations in neural stem cells (NSCs) may be an important part of Alzheimers disease pathogenesis. The phosphatidylinositol 3-kinase (PI3K) pathway has been suggested to play an important role in neuronal cell survival and is highly involved in adult neurogenesis. Recently, coenzyme Q10 (CoQ10) was found to affect the PI3K pathway. We investigated whether CoQ10 could restore amyloid β (Aβ)25-35 oligomer-inhibited proliferation of NSCs by focusing on the PI3K pathway. To evaluate the effects of CoQ10 on Aβ25-35 oligomer-inhibited proliferation of NSCs, NSCs were treated with several concentrations of CoQ10 and/or Aβ25-35 oligomers. BrdU labeling, Colony Formation Assays, and immunoreactivity of Ki-67, a marker of proliferative activity, showed that NSC proliferation decreased with Aβ25-35 oligomer treatment, but combined treatment with CoQ10 restored it. Western blotting showed that CoQ10 treatment increased the expression levels of p85α PI3K, phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3β (Ser9), and heat shock transcription factor, which are proteins related to the PI3K pathway in Aβ25-35 oligomers-treated NSCs. To confirm a direct role for the PI3K pathway in CoQ10-induced restoration of proliferation of NSCs inhibited by Aβ25-35 oligomers, NSCs were pretreated with a PI3K inhibitor, LY294002; the effects of CoQ10 on the proliferation of NSCs inhibited by Aβ25-35 oligomers were almost completely blocked. Together, these results suggest that CoQ10 restores Aβ25-35 oligomer-inhibited proliferation of NSCs by activating the PI3K pathway.

Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson's disease.

BACKGROUND Numerous animal studies and clinical trials have demonstrated that erythropoietin (EPO) has therapeutic effects in ischemic and degenerative diseases. However, few clinical trials have investigated the effect of EPO in Parkinsons disease (PD) patients. This study was an exploratory pilot study to investigate the effects of recombinant human EPO (rhEPO) on motor and non-motor symptoms (NMS) in PD patients. METHODS A total of 26 PD patients at the Hanyang University Hospital were enrolled in the study. The participants were randomly assigned to rhEPO and placebo groups. The rhEPO group was infused intravenously (40,000 IU each) twice a week for 5 weeks. Clinical improvement was estimated using the Unified Parkinsons Disease Rating Scale-III (UPDRS-III), the NMS Scale (NMSS) and the 39-Item Parkinsons Disease Questionnaire (PDQ-39). [(18)F] N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) photon emission tomography (PET) scanning was performed on each participant at baseline and again after 12 months. RESULTS The rhEPO administration significantly improved the NMSS and PDQ-39 scores at 12 months. The UPDRS-III, which reflects motor function, did not change significantly after the rhEPO treatment. With the NMSS, the domains of cardiovascular autonomic function, sleep/fatigue, mood/cognition and attention/memory showed significant changes. None of the participants experienced any serious adverse effects. DISCUSSION We found that rhEPO had beneficial effects on NMS but not on motor function. Dopaminergic refractory NMS, such as cardiovascular autonomic dysfunction and cognition, showed improvement after the administration of rhEPO. Our results suggest that rhEPO might be a good candidate for the treatment of NMS in PD patients.

Additional role of sarcopenia to waist circumference in predicting the odds of metabolic syndrome.

BACKGROUND & AIMS It is unclear whether sarcopenia contributes to the prediction of metabolic dysregulations in addition to that predicted by waist circumference. METHODS Subjects consisted of 6832 adult participants in the 2009 Korea National Health and Nutrition Examination Survey, grouped into categories of waist circumference (normal vs. high). Sarcopenia was assessed by appendicular skeletal muscle mass divided by weight. RESULTS In the normal waist circumference category, the risk of metabolic syndrome was nearly 3.5-fold higher in sarcopenic men (OR, 3.39; 95% CI, 1.67-6.90) than in those without sarcopenia. For the high waist circumference category, the risk of metabolic syndrome was 2.5-fold higher in sarcopenic women (OR, 2.37; 95% CI, 1.66-3.40) than in those without sarcopenia. The corresponding risk was also higher in sarcopenic men (OR, 1.81; 95% CI, 1.11-2.94) than in those without sarcopenia. With the exception in men with high waist circumference category, adjustments for other potential confounders did not substantially affect the results. Appendicular skeletal muscle mass divided by weight as a continuous variable was also associated with metabolic syndrome in men (OR, 0.39; 95% CI, 0.35-0.44) and women (OR, 0.53; 95% CI, 0.48-0.60). CONCLUSIONS Sarcopenia is associated with metabolic syndrome in men with normal waist circumference and women with high waist circumference. Our results emphasize that sarcopenia may contribute additionally to the risk of metabolic abnormalities beyond what is predicted by the abdominal obesity category.

Aminotransferase upper reference limits and the prevalence of elevated aminotransferases in the Korean adolescent population.

Objectives: For the pediatric population, upper reference limits (URLs) for aminotransferase levels have not been established. The prevalence of high aminotransferase levels provides important information regarding the burden of liver disease in the current childhood obesity endemic. Methods: We set the URL of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for participants ages 10 to 19 years (n = 2746) from the 2007 to 2009 Korea National Health and Nutrition Examination Survey at the 97.5th percentile of that population who were determined to be at low risk for liver disease (n = 1717; low risk was defined as testing negative for hepatitis B virus surface antigens, the absence of alcohol use disorder, having normal body mass index, and having normal lipid or carbohydrate metabolism). Results: The URLs for ALT were 33 IU/L for boys and 25 IU/L for girls, and the corresponding limits for AST were 33 IU/L for boys and 28 IU/L for girls. The weighted prevalence of elevated ALT levels was 6.5% in the sample, 8.2% in boys and 4.5% in girls. The prevalence of elevated AST levels was 3.9% and had no sex differences. We also found that elevated ALT levels are associated with male sex, older age, obesity, and presence of abnormal lipid levels. Having elevated AST levels is associated with obesity, younger age, and exhibiting laboratory indicators of abnormal lipid metabolism. Conclusions: Aminotransferase URLs are being established for the first time, and our results may be useful in determining a baseline level for monitoring the secular trends of liver disease in future studies of adolescent populations.

A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is managed with valproate in most patients; however, valproate is an antiepileptic drug that has relatively severe adverse effects, especially in women. We performed a prospective, open-label, randomized observational study for comparison of efficacy and tolerability between topiramate and valproate in patients with JME. The inclusion criteria were patients with newly diagnosed JME or previously diagnosed JME with a history of a poor response or adverse effects to other antiepileptic drugs. The primary endpoint of this study was percentage of patients who were free of myoclonic seizures for 24 weeks in the two groups. The frequency and severity of adverse effects were also assessed. Sixteen patients were randomized to topiramate and 17 to valproate. In the topiramate arm, 11 of 16 patients (68.9%) completed 24-week maintenance therapy and seven of the 11 (64%) were seizure-free. In the valproate arm, 16 of 17 patients (94.1%) completed 24-week follow-up and nine of 16 (56%) were seizure-free. The difference (64% topiramate versus 56% valproate) did not reach statistical significance in this study group (p = 0.08, Fishers exact test). However, the severity of adverse effects was significantly different. Only 1 of 10 adverse effects from topiramate was ranked moderate-to-severe (10%), in comparison with severe rankings for 10 of 17 adverse effects from valproate (59%) (p = 0.018, Fishers exact test). In summary, the efficacy of topiramate and valproate was not different, but the severity of adverse effects was favourable for topiramate. Our findings suggest that valproate may be replaced with topiramate, especially for the patients with JME who do not tolerate valproate.

Movement Disorders Following Cerebrovascular Lesion in the Basal Ganglia Circuit

Movement disorders are primarily associated with the basal ganglia and the thalamus; therefore, movement disorders are more frequently manifest after stroke compared with neurological injuries associated with other structures of the brain. Overall clinical features, such as types of movement disorder, the time of onset and prognosis, are similar with movement disorders after stroke in other structures. Dystonia and chorea are commonly occurring post-stroke movement disorders in basal ganglia circuit, and these disorders rarely present with tremor. Rarer movement disorders, including tic, restless leg syndrome, and blepharospasm, can also develop following a stroke. Although the precise mechanisms underlying the pathogenesis of these conditions have not been fully characterized, disruptions in the crosstalk between the inhibitory and excitatory circuits resulting from vascular insult are proposed to be the underlying cause. The GABA (gamma-aminobutyric acid)ergic and dopaminergic systems play key roles in post-stroke movement disorders. This review summarizes movement disorders induced by basal ganglia and thalamic stroke according to the anatomical regions in which they manifest.

Brain morphology in juvenile myoclonic epilepsy and absence seizures

We evaluated the differences in brain morphology among patients with juvenile myoclonic epilepsy according to the occurrence of absence seizures.

Olfactory dysfunction in early Parkinson’s disease is associated with short latency afferent inhibition reflecting central cholinergic dysfunction

OBJECTIVE Our study aimed to determine whether the short latency afferent inhibition (SAI) response could be associated with the severity of olfactory dysfunction in PD patients. METHODS A total of 71 PD patients and 20 controls were enrolled. All PD patients were classified into 3 groups by the severity of the olfactory deficit. Single-pulse transmagnetic stimulation (TMS) parameters and SAI were assessed. RESULTS The integrated SAI in the PD with anosmia and PD with hyposomia groups was significantly less inhibited than that in the PD with normosmia and control groups [64.79 {Interquartile range (IQR): 59.96, 71.33}, 84.79 {IQR: 75.03, 90.63} versus 36.72 {IQR: 32.28, 48.33}, 42.15 {IQR: 34.60, 44.96}, respectively]. In PD subjects, the severity of olfactory dysfunction also showed a significant negative correlation with the SAI response (r=-0.829, p<0.001). CONCLUSIONS Considering that the SAI response partly reflects central cholinergic dysfunction and that our study shows a relationship between the SAI response and the severity of olfactory dysfunction in PD, our findings indicate that cholinergic dysfunction could possibly contribute to the pathogenesis of olfactory dysfunction in early PD. SIGNIFICANCE SAI could be a useful marker to detect severe olfactory dysfunction in PD.

Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease.

Background and Objectives: Gastrointestinal dysfunction is a common non motor symptom in Parkinsons disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying. Methods: Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T1/2) was determined. The PD patients were divided into a delayed-GET group and a normal-GET group. Results: The serum 25-hydroxyvitamin D3 levels were decreased in the delayed-GET group compared with the normal-GET and control groups (11.59 ± 4.90 vs. 19.43 ± 6.91 and 32.69 ± 4.93, respectively, p < 0.01). In the multivariate model, the serum 25-hydroxyvitamin D3 level was independently associated with delayed gastric emptying in PD patients. Conclusions: Vitamin D status may be an independent factor for gastric dysmotility in PD. Although the underlying mechanism remains to be characterized, vitamin D status may play a role in the pathogenesis of delayed gastric emptying in drug-naive PD.

The effects of additional arm weights on arm-swing magnitude and gait patterns in Parkinson’s disease

OBJECTIVE Recently, arm facilitation has been interested in gait rehabilitation. However, there have been few studies concerning arm facilitation in patients with Parkinsons disease (PD). The aim of our study was to investigate the effect of increasing arm weights on gait pattern in patients with PD. METHODS Twenty-seven patients with PD were enrolled, and they underwent gait analysis using a three-dimensional motion capture system. Sandbags were applied to the distal forearms in all participants. We compared gait parameters including arm swing, pelvic motion, spatiotemporal data, and relative rotational angle between the weighted and unweighted gaits. RESULTS The total arm-swing amplitude and pelvic rotation were significantly higher when walking with additional arm weights than without arm weights. Cadence, walking speed, stride length, and swing phase were significantly higher, whereas stride time, double-support time, and stance phase were significantly lower, when walking with additional arm weights than without arm weights. CONCLUSIONS We conclude that adding weights to the arm during walking may facilitate arm and pelvic movements, which results in changes to gait patterns. The therapeutic use of additional arm weights could be considered for gait rehabilitation in PD to improve gait impairment. SIGNIFICANCE Arm-swing facilitation using weight load improved gait in Parkinsons disease.