ABSTRACT
Huntington's disease (HD) is a deadly neurodegenerative disease with abnormal expansion of CAG repeats in the huntingtin gene. Mutant Huntingtin protein (mHTT) forms abnormal aggregates and intranuclear inclusions in specific neurons, resulting in cell death. Here, we tested the ability of a natural heat-shock protein 90 inhibitor, Gedunin, to degrade transfected mHTT in Neuro-2a cells and endogenous mHTT aggregates and intranuclear inclusions in both fibroblasts from HD patients and neurons derived from induced pluripotent stem cells from patients. Our data showed that Gedunin treatment degraded transfected mHTT in Neuro-2a cells, endogenous mHTT aggregates and intranuclear inclusions in fibroblasts from HD patients, and in neurons derived from induced pluripotent stem cells from patients in a dose- and time-dependent manner, and its activity depended on the proteasomal pathway rather than the autophagy route. These findings also showed that although Gedunin degraded abnormal mHTT aggregates and intranuclear inclusions in cells from HD patient, it did not affect normal cells, thus providing a new perspective for using Gedunin to treat HD.
ABSTRACT
ObjectiveTo investigate the effect and medical cost of different revascularization strategies for acute myocardial infarction (AMI) patients with multi-vessel disease (MVD).Methods A prospective randomized controlled trial (RCT) was conducted. From January 2009 to June 2012, patients with AMI and MVD undergoing primary percutaneous coronary intervention (PCI) were enrolled. They were randomly assigned to group A [staged PCI for non-infarction related artery (non-IRA) within 7-10 days after AMI] and group B (subsequent PCI for non-IRA recommended only for those with evidence of ischemia). All of patients were given optimized medical therapy according to clinical guideline, and they were followed up for 24 months at regular intervals. Major adverse cardiovascular events(MACE) including recurrence of myocardial infarction and death due to cardiac ailments were recorded. Meanwhile, re-hospitalization from cardiac causes, recurrence of angina, heart failure, and re-PCI, number of stents, total hospital stay days, and total medical expenditure were recorded.Results A total of 428 patients accomplished the 24-month follow up. All the patients underwgennt PCI for non-IRA in group A (215 patients), while 62 patients in group B (213 patients) undergone PCI for myocardial ischemia, and 51 patients received non-IRA treatment. There was no significant difference in MACE incidence between group A and group B [8.4% (18/215) vs. 10.8% (23/213),χ2= 0.727,P = 0.394]. The difference of death rate due to cardiac causes (5.1% vs. 6.6%), recurrence of myocardial infarction (4.2% vs. 6.6%), and heart failure (4.2% vs. 7.0%) were not significantly different between groups A and B (allP> 0.05). The rate of recurrence of angina (14.4 % vs. 32.9%), re-hospitalization from cardiac causes (14.4% vs. 33.8%), and re-treatment of implanting stents (12.6% vs. 29.1%) were significantly lower in group A than group B (allP< 0.01), and the rate of revascularization was significantly higher in group A than group B (10.7% vs. 5.2%,P< 0.05). The total number of stents (610 vs. 366), mean number of stents per patient (2.83±0.91 vs. 1.72±0.91,t = 12.725,P = 0.000), and total cost per patient (kRMB: 63.7±12.6 vs. 51.5±12.3,t = 10.107,P = 0.000) in group A were significantly higher than those in group B. Total hospital stay days in group A was significantly less than group B (days: 8.21±2.45 vs. 9.89±3.23, t = 6.071,P = 0.000). Because non-IRA-vascular reconstruction rate was low in group B, the rate of usingβ-blocker and anti-anginal agents during the 24-month follow up in group B was significantly higher than group A [59.2% (126/213) vs. 47.0% (101/215),χ2= 6.371,P = 0.012; 56.3% (112/213) vs. 17.6% (36/215),χ2 = 64.704,P = 0.000]. Conclusions In patients with AMI and MVD undergone emergency PCI, staged PCI within 7-10 days for non-IRA cannot decrease the incidence of myocardial infarction and death due to cardiac causes, recurrence of angina and rehospitalization for cardiac causes was diminished, and it may increase the number of stents and medical cost significantly.
ABSTRACT
Objective To explore the impact of a“one-week”staged multivessel percutaneous coronary intervention (PCI) versus culprit-only PCI on deaths and major adverse cardiac events (MACE). Methods We retrospectively analyzed 447 patients with multivessel disease who experienced a ST-segment elevation myocardial infarction (STEMI) within 12 h before undergoing PCI between July 26, 2008 and Septem-ber 25, 2011. After completion of PCI in the infarct artery, 201 patients still in the hospital agreed to undergo PCI in non-infarct arteries with more than 70%stenosis for a“one-week”staged multivessel PCI. A total of 246 patients only received intervention for the culprit vessel. Follow-up ended on September 9, 2014. This study examined the differences in deaths from any cause (i.e., cardiac and noncardiac) and MACE between the two treatment groups. Results Compared to a culprit-only PCI treatment approach, the“one-week”staged multivessel PCI was strongly associated with greater benefits for 55-month all cause death [41 (16.7%) vs.13 (6.5%), P=0.004] and MACE [82 (33.3%) vs. 40 (19.9%), P=0.002] rates. In addition, there were significant differences in the number of myocardial infarctions [43 (17.5%) vs. 20 (10.0%), P=0.023], coronary-artery bypass grafting [CABG;20 (8.1%) vs. 6 (3.0%), P=0.021], and PCI [31 (12.6%) vs. 12 (6.0%), P=0.018]. Patients undergoing culprit-only PCI compared to“one-week”PCI had the same number of stent thrombosis events [7 (2.8%) vs. 3 (1.5%), P=0.522]. Conclusions Compared to a culprit-only PCI treatment approach,“one-week”staged multi-vessel PCI was a safe and effective selection for STEMI and multi-vessel PCI.
ABSTRACT
To evaluate the long-term results in elderly patients undergoing percutaneous coronary intervention [PCI] with drug-eluting stents for unprotected left main coronary artery disease by transradial approach. This study took place in Qinhuangdao First Hospital, Hebei Medical University, Hebei, China between October 2006 and December 2009. Seventy-nine elderly patients with unprotected left main coronary artery [ULMCA] stenosis, aged >/= 70 years, that underwent drug-eluting stent were evaluated. The occurrence of major adverse cardiac events [MACE] [death, non-fatal myocardial infarction, stroke or target lesion revascularizations] was recorded after 3 years of follow-up. After 3 years follow-up, the MACE free survival rate was 72.2%. Cardiac deaths occured in 7.6% of patients. Myocardial infarction occurred in 5.1%, and target lesion revascularization in 13.9% of patients. Age and left main distal bifurcation were favorable predictors of MACE. Percutaneous coronary intervention can be performed with good angiographic and clinical results through a transradial approach in the elderly. The long term survival suggests that PCI in ULMCA patients >/= 70 years is safe and efficacious
Subject(s)
Humans , Male , Female , Coronary Artery Disease/surgery , Stents , Coronary Stenosis/surgery , Coronary Angiography , Percutaneous Coronary Intervention , Aged , Retrospective StudiesABSTRACT
It has been known that the Alzheimer's disease(AD)is related closely with a synaptic failure,and the p21-activated kinase(PAK)is well documented to play an important role in the regulation of the synaptie functions.However,the relationship between thePAK and the pathology of AD is unclear.In the present study,we examined the expressions of the PAK3(one subtype ofPAK),phospho-rylated-PAK(pPAK) and β-amyloid42(Aβ42,β-amyloid with 42 peptides)in an APP/PS1 double transgenie mouse model of AD andthe morphologies of geurOtlS in the hippocampus at different ages.The Western Blot results showed that the expression of PAK remainedunchanged,while,the expression of pPAK decreased largely at the age of 32 weeks and further decreased significantly with aging in thehippocampus of the APP/PS1 transgenic mouse.A1342 levels in the hippocampus were detected to increase as early as the age of 22 weeks,and kept the increase to continue with aging.The morphological results showed no obvious neuron loss in the sections of Nissl staining,while serious distonion and disorder of the dendrites of the hippocampal neurons were observed on the sections of Gelgi staining in theAPP/PS1 transgenic mouse.The present results suggested that it seemed something wrong in the processes of phospholization of PAK,butnot in the expression of the PAK itself;the toxic Aβ42 might affect the PAK in its phospholization,which in turn directly influence thedendritic development in the hippocampal neurons and cause the dendrites distorting and disordering.