Results:The 30-day mortality was 2•6% in AAD and 7•5% in CAD.The 30-day stroke and paraplegia rates were 5•3% and 0% in AAD and zero in patients with CAD.At 30 months, the cumulative re-intervention rate was 62% and 55% in AAD and CAD, respectively.In AAD, at 12 months, the false lumen thrombosis rate was 85% at the stent and 60% below it.In CAD, thrombosis rates were 68% above the stent and 33% below it.Conclusion: Aortic remodelling is greater in AAD.In AAD and in the segment, for both dissection types, false lumen thrombosis rates are higher.In AAD and CAD there is a significant re-intervention rate.The length of aorta covered with the stent should be greater, particularly in CAD.Robotic endovascular catheters (REC) improve accuracy, reduce time and minimise radiation exposure in complex vascular procedures
Acute dissection is the most common life threatening condition of the aorta affecting 5-30 per million people per year [1]. Left untreated, the majority of patients with dissections involving the ascending aorta will die within days of an acute episode [2]. Patients presenting with descending thoracic aortic dissections seem to fare better, with one in ten patients dying before leaving hospital. Ultimately, these patients are at risk of aortic rupture with nearly 20% of these patients requiring some form of surgical or endovascular intervention [3]. Judicious medical, surgical and endovascular management of this condition aims to reduce propagation of the dissection plane and concomitant branch vessel compromise, halt aortic expansion and prevent fatal aortic rupture. Early recognition of these disease entities in conjunction with urgent and pertinent management is the key to a successful outcome in these patients. Keywords: Aneurysm, dissecting, antihypertensive agents, aortic aneurysm, aortic rupture, endovascular, stent grafts, risk factors, surgery, treatment outcome
Cadmium (Cd) is an environmental contaminant, which is a potential risk factor in the progression of aging-associated neurodegenerative diseases. Herein, we have assessed the effects of chronic administration of Cd on cellular oxidative stress and its associated Alzheimer's disease (AD) pathologies in animal models. Two groups of mice were used, one group administered with saline and the other with Cd (1 mg/kg/day; intraperitoneally) for 3 months. After behavioral studies, molecular/biochemical (Immunoblotting, ELISAs, ROS, LPO, and GSH assays) and morphological analyses were performed. We observed an exacerbation of memory and synaptic deficits in chronic Cd-injected mice. Subacute and chronic Cd escalated reactive oxygen species (ROS), suppressed the master antioxidant enzymes, e.g., nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1, and evoked the stress kinase phospho-c-Jun N-terminal kinase 1 signaling pathways, which may escalate AD pathologies possibly associated with amyloidogenic processes. These findings suggest the regulation of oxidative stress/ROS and its associated amyloid beta pathologies for targeting the Cd-exacerbated AD pathogenesis. In addition, these preclinical animal studies represent a paradigm for epidemiological studies of the human population exposed to chronic and subacute administration of Cd, suggesting avoiding environmental contaminants.
Abstract Background Carotid endarterectomy reduces the risk of stroke and death in patients with severe carotid artery stenosis. This study examined whether the technique used to close the arteriotomy influenced the rate of perioperative transient ischaemic attack (TIA), stroke or death. Methods A cohort of 236 patients undergoing carotid endarterectomy at a single centre was studied; 117 patients had primary closure of the arteriotomy and 119 patients in a sequential series had closure with a Dacron® patch. A standard endarterectomy with completion intraoperative duplex imaging and digital subtraction angiography was used throughout. Results Patch closure was associated with a significant reduction in the 30-day combined death, stroke and TIA rate: 10·3 per cent for primary closure versus 2·5 per cent for patch closure (P = 0·017). The risk of any cerebral event (stroke or TIA) was also significantly reduced (7·7 versus 1·7 per cent; P = 0·033). Residual stenosis on completion angiography was more common after primary closure (24·6 versus 7·4 per cent; P = 0·003). Conclusion Dacron® patch closure had a higher technical success rate on completion imaging and was associated with a significant reduction in the risk of perioperative stroke, TIA and death.
: Natural products have been the focus of biomedical and pharmaceutical research to develop new therapies in recent years. 2-methoxy-6-acetyl-7-methyljuglone (2-methoxystypandrone, MAM) a natural bioactive juglone derivative, is known to have various levels of pharmacotherapeutic efficacies as an anti-inflammatory, anticancer, antioxidant, antimicrobial, and anti-HIV activities. MAM fights cancer progression by inducing apoptosis, necroptosis and deregulating signaling pathways through H2O2-induced JNK/iNOS/NO and MAPK, ERK1/2 pathways, JNK activation, and the RIP1/RIP3 complex. In this review, we summarize the pharmacological importance of MAM in the field of drug discovery. Furthermore, this review not only emphasizes the medicinal properties of MAM, but also discusses its potential efficacy in future medicinal products.
Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countries. It is characterized by permanent or transient cerebral ischemia and it activates syndrome of pathological events such as membrane depolarization, glutamate excitotoxicity, and intracellular calcium buildup. Carveol is widely employed as anti-inflammatory and antioxidant in traditional Chinese medicine. In the present study, the neuroprotective effects of post-treated carveol were demonstrated against transient middle cerebral artery occlusion (MCAO) induced focal ischemic cerebral injury. Male Sprague Dawley (SD) rats were subjected to two different experimental protocols to determine the dose and effects of carveol, and to demonstrate the underlying role of the nuclear factor E2-related factor (Nrf2) pathway. Our results showed that MCAO induced marked neuronal injury in the ipsilateral cortex and striatum associated with higher inflammatory cytokines expression, along with apoptotic markers such as caspase-3 and the phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, MCAO induced a marked increase in oxidative stress as evidenced by high lipid peroxidase (LPO) content accompanied by the depressed antioxidant system. Carveol significantly reversed the oxidative stress and downregulated inflammatory cascades by enhancing endogenous antioxidant mechanisms including the Nrf2 gene, which critically regulates the expression of several downstream antioxidants. Further, to determine the possible involvement of Nrf2 in carveol mediated neuroprotection, we antagonized Nrf2 by all-trans retinoic acid (ATRA), and such treatment abrogated the protective effects of carveol accompanied with exaggerated neuronal toxicity as demonstrated by higher infarction area. The target effects of carveol were further supported by molecular docking analysis of drug-protein interactions. Together, our findings suggest that carveol could activate endogenous master anti-oxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating MCAO-induced neuroinflammation and neurodegeneration.
Abstract Toll-like receptor 4 (TLR4) signaling in the brain mediates autoimmune responses and induces neuroinflammation that results in neurodegenerative diseases, such as Alzheimer’s disease (AD). The plant hormone osmotin inhibited lipopolysaccharide (LPS)-induced TLR4 downstream signaling, including activation of TLR4, CD14, IKKα/β, and NFκB, and the release of inflammatory mediators, such as COX-2, TNF-α, iNOS, and IL-1β. Immunoprecipitation demonstrated colocalization of TLR4 and AdipoR1 receptors in BV2 microglial cells, which suggests that osmotin binds to AdipoR1 and inhibits downstream TLR4 signaling. Furthermore, osmotin treatment reversed LPS-induced behavioral and memory disturbances and attenuated LPS-induced increases in the expression of AD markers, such as Aβ, APP, BACE-1, and p-Tau. Osmotin improved synaptic functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95, SNAP-25, and syntaxin-1. Osmotin also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1 and caspase-3. Overall, our studies demonstrated that osmotin prevented neuroinflammation-associated memory impairment and neurodegeneration and suggest AdipoR1 as a therapeutic target for the treatment of neuroinflammation and neurological disorders, such as AD.
Melatonin acts as a pleiotropic agent in various age-related neurodegenerative diseases. In this study, we examined the underlying neuroprotective mechanism of melatonin against D-galactose-induced memory and synaptic dysfunction, elevated reactive oxygen species (ROS), neuroinflammation and neurodegeneration. D-galactose was administered (100 mg/kg intraperitoneally (i.p.)) for 60 days. After 30 days of D-galactose administration, vehicle (same volume) or melatonin (10 mg/kg, i.p.) was administered for 30 days. Our behavioral (Morris water maze and Y-maze test) results revealed that chronic melatonin treatment alleviated D-galactose-induced memory impairment. Additionally, melatonin treatment reversed D-galactose-induced synaptic disorder via increasing the level of memory-related pre-and postsynaptic protein markers. We also determined that melatonin enhances memory function in the D-galactose-treated mice possibly via reduction of elevated ROS and receptor for advanced glycation end products (RAGE). Furthermore, Western blot and morphological results showed that melatonin treatment significantly reduced D-galactose-induced neuroinflammation through inhibition of microgliosis (Iba-1) and astrocytosis (GFAP), and downregulating other inflammatory mediators such as p-IKKβ, p-NF-K B65, COX2, NOS2, IL-1β, and TNFα. Moreover, melatonin lowered the oxidative stress kinase p-JNK which suppressed various apoptotic markers, that is, cytochrome C, caspase-9, caspase-3 and PARP-1, and prevent neurodegeneration. Hence, melatonin attenuated the D-galactose-induced memory impairment, neuroinflammation and neurodegeneration possibly through RAGE/NF-K B/JNK pathway. Taken together, our data suggest that melatonin could be a promising, safe and endogenous compatible antioxidant candidate for age-related neurodegenerative diseases such as Alzheimer's disease (AD).
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