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vascular parkinism

Audrey Swiader, Hripsime Nahapetyan, Julien Faccini, Romina D'Angelo, Elodie Mucher, Meyer Elbaz, Patricia Boya, Cécile Vindis
Mitophagy is a critical cellular process that selectively targets damaged mitochondria for autophagosomal degradation both under baseline conditions and in response to stress preventing oxidative damage and cell death. Recent studies have linked alterations in mitochondria function and reduced autophagy with the development of age-related pathologies. However, the significance of mitochondrial autophagy in vessel wall in response to atherogenic lipid stressors is not known. In the present study, we investigated the role of mitophagy on human vascular smooth muscle cells (VSMC) apoptosis induced by oxidized low-density lipoproteins (LDL)...
May 17, 2016: Oncotarget
Yao Lu, Su Li, Hengfang Wu, Zhiping Bian, Jindan Xu, Chunrong Gu, Xiangjian Chen, Di Yang
Angiotensin II (Ang II)-induced mitochondrial dysfunction is a prominent characteristic of the majority of cardiovascular diseases. Astragaloside IV (As-IV), the major active ingredient of Astragalus membranaceus (Fisch.) Bge. (a traditional Chinese herbal medicine), possesses antioxidant properties. The present study was carried out to examine whether As-IV can reverse Ang II-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs) and to elucidate the underlying molecular mechanisms. Cultured rat aortic VSMCs treated with Ang II (1 µM) for 24 h exhibited mitochondrial dysfunction, including a decrease in mitochondrial oxygen consumption rates (OCRs), adenosine triphosphate (ATP) production and mitochondrial DNA (mtDNA) levels, as well as the disruption of mitochondrial structural integrity...
November 2015: International Journal of Molecular Medicine
Weiwei Wu, Hao Xu, Zemin Wang, Yun Mao, Liangshuai Yuan, Wei Luo, Zhaoqiang Cui, Taixing Cui, Xing Li Wang, Ying H Shen
Mitochondrial injury and dysfunction, a significant feature in metabolic syndrome, triggers endothelial cell dysfunction and cell death. Increasing evidence suggests that mitophagy, a process of autophagic turnover of damaged mitochondria, maintains mitochondrial integrity. PINK1 (phosphatase and tensin homolog (PTEN)-induced putative kinase 1) and Parkin signaling is a key pathway in mitophagy control. In this study, we examined whether this pathway could protect mitochondria under metabolic stress. We found that palmitic acid (PA) induced significant mitophagy and activated PINK1 and Parkin in endothelial cells...
2015: PloS One
Vincenzo Donadio, Alex Incensi, Valentina Leta, Maria Pia Giannoccaro, Cesa Scaglione, Paolo Martinelli, Sabina Capellari, Patrizia Avoni, Agostino Baruzzi, Rocco Liguori
OBJECTIVE: To investigate (1) whether phosphorylated α-synuclein deposits in skin nerve fibers might represent a useful biomarker for idiopathic Parkinson disease (IPD), and (2) the underlying pathogenesis of peripheral neuropathy associated with IPD. METHODS: Twenty-one well-characterized patients with IPD were studied together with 20 patients with parkinsonisms assumed not to have α-synuclein deposits (PAR; 10 patients fulfilling clinical criteria for vascular parkinsonism, 6 for tauopathies, and 4 with parkin mutations) and 30 controls...
April 15, 2014: Neurology
Yasmine F Ibrahim, Chi-Ming Wong, Ludmila Pavlickova, Lingling Liu, Lobsang Trasar, Geetanjali Bansal, Yuichiro J Suzuki
BACKGROUND: Pulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension. METHODS AND RESULTS: After developing pulmonary vascular remodeling in chronic hypoxia or chronic hypoxia/SU-5416 models, rats were injected with antitumor drugs including proteasome inhibitors (bortezomib and MG-132) and daunorubicin...
2014: Journal of the American Heart Association
Claudia Maria Miranda Santos
Although researchers are pursuing "disease modifying" medications to slow or stop Parkinson's disease (PD) progression, a myriad of agents with protective properties in cell cultures and animal models have yielded few treatments in clinical practice. Developing safe and effective treatments with disease-modifying/neuroprotective mechanisms of action and identifying patients in the pre-motor phase will be a challenge. The implication of tyrosine hydroxylase (TH), the enzyme that catalyzes the formation of L-3,4-dihydroxyphenylalanine, in the pathogenesis of PD at different levels makes it a promising candidate for developing efficient treatment based on correcting or bypassing the enzyme deficiency...
June 1, 2012: CNS & Neurological Disorders Drug Targets
Calvin W S Yeo, Felicia S L Ng, Chou Chai, Jeanne M M Tan, Geraldene R H Koh, Yuk Kien Chong, Lynnette W H Koh, Charlene S F Foong, Edwin Sandanaraj, Joanna D Holbrook, Beng-Ti Ang, Ryosuke Takahashi, Carol Tang, Kah-Leong Lim
Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G(1) phase cell-cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo...
May 15, 2012: Cancer Research
Benjamin Gesundheit, Patricia Parkin, Mark Greenberg, Sylvain Baruchel, Christof Senger, Josef Kapelushnik, Charles Smith, Giannoula Lakka Klement
PURPOSE: The role of angiogenesis in the transformation of peripheral neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) in neurofibromatosis type 1 (NF1) remains elusive and forms the objective of this study. EXPERIMENTAL DESIGN: Archival tissue from 5 children with NF1 and PNF, who developed MPNST between the ages of 8 and 15 years were analyzed for differences in microvasculature. The role of proangiogenic growth factors such as Vascular Endothelial Growth Factor (VEGF), and its receptors Flk-1 and Flt-1, and vessel maturity, defined as von Willebrand factor (vWf), α-smooth muscle actin+ (SMA+), were evaluated by immuno-histochemistry...
October 2010: Journal of Pediatric Hematology/oncology
David Rea, John F Brandsema, Derek Armstrong, Patricia C Parkin, Gabrielle deVeber, Daune MacGregor, William J Logan, Rand Askalan
OBJECTIVE: Cerebrovascular abnormalities are serious but underrecognized complications of neurofibromatosis type 1 (NF1). The aim of this study was to investigate the prevalence, clinical presentation, imaging findings, and prognosis of cerebral arteriopathies in childhood NF1. METHODS: Patients followed at the NF1 clinic at the Hospital for Sick Children, Toronto, Ontario, Canada, between 1990 and 2007 were studied. Patients with confirmed NF1 diagnosis and neuroimaging results were included...
September 2009: Pediatrics
Ioannis Mavrikakis, Nick Francis, Cornelia Poitelea, Ben Parkin, Paul Brittain, Jane Olver
PURPOSE: To report the histopathologic findings of explanted Medpor lower eyelid spacers (LES) in complicated cases. MATERIALS AND METHODS: Four cases of lower eyelid retraction due to thyroid orbitopathy (n = 2), facial nerve palsy (n = 1), and post-enucleation socket syndrome (n = 1) were treated with Medpor LES. RESULTS: All implants were removed between 6 months to 2 years following their original insertion due to exposure, poor stability, or contour...
2009: Orbit
William Geoffrey Parkin, Mark Stephen Leaning
By regarding the circulation from the perspective of the venous return, continuous therapeutic control of the mean arterial blood pressure, cardiac output and tissue oxygen flow can be seen to be the consequence of a series of equations based on conventionally measured variables. This approach permits a graphical solution to circulation guidance, open or closed loop control and goal directed therapy of broad general applicability.
December 2008: Journal of Clinical Monitoring and Computing
B Herting, S Bietenbeck, K Scholz, A Hähner, T Hummel, H Reichmann
Olfactory dysfunction is a prominent symptom in Parkinson's disease (PD) and found in about 70-100% of patients. In earlier studies significant loss of olfactory function seemed to be unrelated to disease duration, did not correlate with motor function, and was uninfluenced by antiparkinsonian medication. We suggest that the increase of dopaminergic cells in the olfactory bulb is responsible for the hyposmia in PD patients. Interestingly, this olfactory dysfunction is not found in progressive supranuclear palsy or corticobasal degeneration...
February 2008: Der Nervenarzt
Wakako Tamo, Tadaatsu Imaizumi, Kunikazu Tanji, Hidemi Yoshida, Shingo Takanashi, Koichi Wakabayashi, Ryosuke Takahashi, Nobutaka Hattori, Kei Satoh
Mutations in the parkin gene are related with early-onset Parkinson's disease. Parkin is identified as an E3-ligase that combines target proteins with ubiquitin. alpha-Synuclein and synphilin-1 are substrates for E3-ligase activity of parkin and considered to be involved in the pathogenesis of Parkinson's disease. We previously demonstrated both alpha-synuclein and synphilin-1 are expressed in vascular endothelial cells (VEC). In the present study, we addressed possible expression of parkin in VEC. Parkin immunoreactivity was detected in vascular endothelial cells in postmortem human brain...
June 4, 2007: Neuroscience Letters
Teresa Vazquez, Marc Rodríguez-Niedenfuhr, Ian Parkin, Fermin Viejo, Jose Sanudo
PURPOSE: This project was to study the different patterns of the anterior tibal and dorsalis pedis arteries in relation to the blood supply of the dorsum of the foot and ankle. METHODS: A reliable sample of 150 human embalmed cadavers was dissected. RESULTS: Four different patterns were identified. The dorsalis pedis artery was most frequently (287 cases, 95.7%) found to be the continuation of the anterior tibial artery distal to the ankle, and lay between the tendon of extensor hallucis and the first tendon of extensor digitorum longus...
March 2006: Arthroscopy: the Journal of Arthroscopic & related Surgery
Regina Katzenschlager, Andrew J Lees
PURPOSE OF REVIEW: Marked olfactory dysfunction (hyposmia) is a frequent and early abnormality in Parkinson's disease. We review recent advances related to its cause and its clinical relevance with respect to the differential diagnosis of Parkinsonian syndromes. RECENT FINDINGS: Marked olfactory dysfunction occurs in Parkinson's disease and dementia with Lewy bodies but is not found in progressive supranuclear palsy and corticobasal degeneration. In multiple system atrophy, the deficit is mild and indistinguishable from cerebellar syndromes of other aetiologies, including the spino-cerebllar ataxias...
August 2004: Current Opinion in Neurology
No abstract text is available yet for this article.
1958: Surgical Forum
Andrew C Brooks, Chryso Kanthou, Ian H Cook, Gillian M Tozer, Paul R Barber, Boris Vojnovic, Gerard B Nash, Charles S Parkins
BACKGROUND: Combretastatin A-4-phosphate (CA-4-P) is a microtubule depolymerising agent currently in clinical trial as a tumour vascular-targeting agent. In vivo, CA-4-P causes rapid shutdown of tumour blood flow (within minutes) and a significant neutrophil infiltration at later times. MATERIALS AND METHODS: Using an in vitro flow-cell assay, we investigated neutrophil-endothelial cell interactions and associated mechanisms, following endothelial cell exposure to CA-4-P...
July 2003: Anticancer Research
Jinghai Sun, Ivana Cecic, Charles S Parkins, Mladen Korbelik
Neutrophils have become recognised as important contributors to the effectiveness of tumour eradication by photodynamic therapy (PDT). In this study, we have used the mouse SCCVII squamous cell carcinoma model to investigate the activity of neutrophils in tumours treated by PDT. Tumour levels of neutrophilic myeloperoxidase (MPO) demonstrated not only a massive and sustained sequestration of these cells in PDT-treated tumours but also revealed their activated state evidenced by the presence of released MPO...
September 2002: Photochemical & Photobiological Sciences
Gillian M Tozer, Chryso Kanthou, Charles S Parkins, Sally A Hill
The tumour vasculature is an attractive target for therapy. Combretastatin A-4 (CA-4) and A-1 (CA-1) are tubulin binding agents, structurally related to colchicine, which induce vascular-mediated tumour necrosis in animal models. CA-1 and CA-4 were isolated from the African bush willow, Combretum caffrum, and several synthetic analogues are also now available, such as the Aventis Pharma compound, AVE8062. More soluble, phosphated, forms of CA-4 (CA-4-P) and CA-1 (CA-1-P) are commonly used for in vitro and in vivo studies...
February 2002: International Journal of Experimental Pathology
Margaret E Watts, Charles S Parkins, David J Chaplin
BACKGROUND: Cell adhesion molecule expression by tumour endothelium is involved in the efficacy of several cancer therapies. This study investigated the effect of tumour microenvironmental conditions, i.e. reduced oxygenation and tumour-conditioned medium (TCM), on the expression of adhesion molecules by HUVECs. MATERIALS AND METHODS: E-selectin (CD62-E), VCAM-1 (CD106) and PECAM-1 (CD31) were measured using an ELISA assay. Reduced oxygen tension (approximately 0%, 1% vs...
March 2002: Anticancer Research
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