scholarly journals Carotid Disease and Ageing: A Literature Review on the Pathogenesis of Vascular Senescence in Older Subjects

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Eleni Sertedaki ◽  
Dimitris Veroutis ◽  
Flora Zagouri ◽  
George Galyfos ◽  
Konstadinos Filis ◽  
...  
Keyword(s):  
Environmental Changes ◽  
Immune Cell ◽  
Current Evidence ◽  
Human Organism ◽  
Atheromatous Plaque ◽  
Biomedical Sciences ◽  
Carotid Disease ◽  
Morphological Alterations ◽  
Symptomatic Carotid ◽  
Vascular Senescence

Aging is a natural process that affects all systems of the human organism, leading to its inability to adapt to environmental changes. Advancing age has been correlated with various pathological conditions, especially cardiovascular and cerebrovascular diseases. Carotid artery (CA) is mainly affected by age-induced functional and morphological alterations causing atheromatous disease. The evolvement of biomedical sciences has allowed the elucidation of many aspects of this condition. Symptomatic carotid disease (CD) derives from critical luminar stenosis or eruption of an atheromatous plaque due to structural modifications of the vessels, such as carotid intima-media thickening. At a histologic level, the aforementioned changes are mediated by elastin fragmentation, collagen deposition, immune cell infiltration, and accumulation of cytokines and vasoconstrictors. Underlying mechanisms include chronic inflammation and oxidative stress, dysregulation of cellular homeostatic systems, and senescence. Thus, there is an imbalance in components of the vessel wall, which fails to counteract exterior stress stimuli. Consequently, arterial relaxation is impaired and atherosclerotic lesions progress. This is a review of current evidence regarding the relationship of aging with vascular senescence and CD. A deeper understanding of these mechanisms can contribute to the production of efficient prevention methods and targeted therapeutic strategies.

scholarly journals Vascular pathology in multiple sclerosis: reframing pathogenesis around the blood-brain barrier

2017 ◽  
Vol 89 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Jonathan I Spencer ◽  
Jack S Bell ◽  
Gabriele C DeLuca
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
Neurological Diseases ◽  
Specific Immune Response ◽  
Brain Barrier ◽  
Vascular Pathology ◽  
Current Evidence ◽  
Blood Brain

Blood-brain barrier (BBB) disruption has long been recognised as an important early feature of multiple sclerosis (MS) pathology. Traditionally, this has been seen as a by-product of the myelin-specific immune response. Here, we consider whether vascular changes instead play a central role in disease pathogenesis, rather than representing a secondary effect of neuroinflammation or neurodegeneration. Importantly, this is not necessarily mutually exclusive from current hypotheses. Vascular pathology in a genetically predisposed individual, influenced by environmental factors such as pathogens, hypovitaminosis D and smoking, may be a critical initiator of a series of events including hypoxia, protein deposition and immune cell egress that allows the development of a CNS-specific immune response and the classical pathological and clinical hallmarks of disease. We review the changes that occur in BBB function and cerebral perfusion in patients with MS and highlight genetic and environmental risk factors that, in addition to modulating immune function, may also converge to act on the vasculature. Further context is provided by contrasting these changes with other neurological diseases in which there is also BBB malfunction, and highlighting current disease-modifying therapies that may also have an effect on the BBB. Indeed, in reframing current evidence in this model, the vasculature could become an important therapeutic target in MS.

scholarly journals The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Elisa Ridolfi ◽  
Cinzia Barone ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Environmental Changes ◽  
Current Evidence ◽  
Neuronal Function ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

scholarly journals LO012: High-risk investigation findings for symptomatic carotid disease in ED TIA patients

CJEM ◽  
2016 ◽  
Vol 18 (S1) ◽  
pp. S34-S34
Author(s):  
N. Motamedi ◽  
K. Abdulaziz ◽  
M. Sharma ◽  
J.J. Perry
Keyword(s):  
Platelet Count ◽  
Blood Glucose ◽  
High Risk ◽  
Carotid Stenosis ◽  
Univariate Analysis ◽  
Carotid Disease ◽  
Multicenter Cohort Study ◽  
Symptomatic Carotid ◽  
Acute Infarction ◽  
Large Vessel Disease

Introduction: About 20% of TIAs are due to large vessel disease. Carotid stenosis >50% which is causing a TIA or stroke needs to be definitely managed quickly in order to benefit. Alternatively, dual antiplatelet therapy may be considered. The objective of this study was to determine high-risk diagnostic findings associated with symptomatic carotid disease in ED patients with TIA to indicate patients requiring urgent carotid imaging. Methods: We performed a prospective Canadian multicenter cohort study, at 13 academic sites, of ED patients with TIA or non-disabling stroke from 2006-2014. Study research nurses recorded imaging findings on standardized data collection forms from the final reports of all imaging tests ordered in the ED on prospectively enrolled patients by treating emergency physicians. Symptomatic carotid disease was defined as carotid stenosis 50-99% or carotid dissection and was adjudicated by stroke neurology to be the etiology of the index event. Patients were followed by medical review and telephone up to 90 days. Univariate analysis was conducted for investigation results with our primary outcome. Results: The cohort included 305 patients with and 5,277 without symptomatic carotid disease. Positive predictors of symptomatic carotid disease included platelet count over 400 x 109/L (15.3% vs 7.6%; p=0.0095), blood glucose >15 mmol/L (11.4% vs 4.4%; p<0.0001), CT evidence of acute infarction (9.8% vs 4.1%; p<0.0001), CT evidence of old infarction (35.7% vs 24.1%; p<0.0001), and CT evidence of any infarct (43.3% vs 26.7%; p<0.0001). There were no negative predictors of symptomatic carotid disease. Conclusion: High-risk investigation findings suggestive of symptomatic carotid disease in ED TIA patients include platelet count over 400 x 109/L, blood glucose >15 mmol/L, CT evidence of any infarction. Patients with any of these findings should be considered for rapid carotid imaging.

scholarly journals Systematic Review and Meta-Analysis of Very Urgent Carotid Intervention for Symptomatic Carotid Disease

2018 ◽  
Vol 68 (6) ◽  
pp. 1959
Author(s):  
D. Milgrom ◽  
S. Hajibandeh ◽  
S. Hajibandeh ◽  
S.A. Antoniou ◽  
F. Torella ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Carotid Disease ◽  
Symptomatic Carotid

scholarly journals Pet dog bites in children: management and prevention

2020 ◽  
Vol 4 (1) ◽  
pp. e000726 ◽  
Author(s):  
Molly Jakeman ◽  
James A Oxley ◽  
Sara C Owczarczak-Garstecka ◽  
Carri Westgarth
Keyword(s):  
Environmental Changes ◽  
Prophylactic Antibiotic ◽  
Public Health Problem ◽  
Antibiotic Use ◽  
Current Evidence ◽  
Dog Bites ◽  
Safe Management ◽  
Significant Public Health ◽  
Careful Exploration ◽  
High Index Of Suspicion

Dog bite injuries are a significant public health problem and many are sustained by children. These injuries can be complex, both physically and psychologically, and in rare cases fatal. This paper will review current evidence-based approaches to treatment, explore identified patterns in biting incidents and discuss the effectiveness of prevention strategies. Safe management of these patients requires a comprehensive approach. Physical injuries need to be accurately assessed with a high index of suspicion for underlying injuries, particularly in younger children less able to communicate. Treatment depends on severity and location, but all bites must be irrigated to reduce the risk of infection but may not always require prophylactic antibiotic use. Careful exploration of the circumstances in which the bite occurred is essential to make safeguarding decisions and prevent future bites. Reducing the incidence of paediatric dog bites requires education of both children and parents that any dog can bite, regardless of breed, and all child–dog interactions must be highly supervised. However, education alone is unlikely to prevent dog bites. Policies that support environmental changes need to be developed such as provision of pet dogs less likely to bite (or bite as severely), through breeding for temperament and appropriate socialisation. Additionally, investment in psychological support for bite victims and their families is required to reduce the long-term impacts of being bitten.

scholarly journals Inflammation in Metabolic Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Florian A. Wenzl ◽  
Samuele Ambrosini ◽  
Shafeeq A. Mohammed ◽  
Simon Kraler ◽  
Thomas F. Lüscher ◽  
...  
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Cardiac Cells ◽  
Calcium Handling ◽  
Current Evidence ◽  
Cardiomyocyte Hypertrophy ◽  
Myocardial Inflammation ◽  
Low Grade ◽  
Metabolic Disturbances ◽  
Nutrient Metabolism

Overlapping pandemics of lifestyle-related diseases pose a substantial threat to cardiovascular health. Apart from coronary artery disease, metabolic disturbances linked to obesity, insulin resistance and diabetes directly compromise myocardial structure and function through independent and shared mechanisms heavily involving inflammatory signals. Accumulating evidence indicates that metabolic dysregulation causes systemic inflammation, which in turn aggravates cardiovascular disease. Indeed, elevated systemic levels of pro-inflammatory cytokines and metabolic substrates induce an inflammatory state in different cardiac cells and lead to subcellular alterations thereby promoting maladaptive myocardial remodeling. At the cellular level, inflammation-induced oxidative stress, mitochondrial dysfunction, impaired calcium handling, and lipotoxicity contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation and microvascular disease. In cardiometabolic patients, myocardial inflammation is maintained by innate immune cell activation mediated by pattern recognition receptors such as Toll-like receptor 4 (TLR4) and downstream activation of the NLRP3 inflammasome and NF-κB-dependent pathways. Chronic low-grade inflammation progressively alters metabolic processes in the heart, leading to a metabolic cardiomyopathy (MC) phenotype and eventually to heart failure with preserved ejection fraction (HFpEF). In accordance with preclinical data, observational studies consistently showed increased inflammatory markers and cardiometabolic features in patients with HFpEF. Future treatment approaches of MC may target inflammatory mediators as they are closely intertwined with cardiac nutrient metabolism. Here, we review current evidence on inflammatory processes involved in the development of MC and provide an overview of nutrient and cytokine-driven pro-inflammatory effects stratified by cell type.

scholarly journals Pitfalls of Animal Study: Avicenna’s View

2016 ◽  
Vol 5 (3) ◽  
pp. 160-161
Author(s):  
Babak Daneshfard ◽  
Vahid Tafazoli ◽  
Majid Nimrouzi
Keyword(s):  
Animal Studies ◽  
Experimental Approach ◽  
Drug Evaluation ◽  
Modern Medicine ◽  
Current Evidence ◽  
Biomedical Sciences ◽  
Negative Results ◽  
Traditional Persian Medicine ◽  
Meta Analyses ◽  
Islamic Golden Age

Dear Editor-in-ChiefUndoubtedly, animal models have an important role in the development of basic biomedical sciences [1]. In addition, preclinical animal studies have been used to determine the safety and efficacy of treatments before conducting human trials [2]. However, there is a growing uncertainty regarding the essentiality of animal studies in progress of medicine [3]. It has been frequently reported that the results of these studies are poorly replicated in human studies even in high-quality animal investigations [3, 4].Regarding the lack of evidence showing the benefits of animal research, poor methodologies, publication bias due to unpublished negative results, and inadequate systematic reviews and meta-analyses of animal studies are the main concerns [5, 2]. Moreover, there are so many obvious and obscure discrepancies between human and animals in different aspects among which, the diversity in their metabolism seems to be the most important one.Nowadays, personalized medicine as a newcomer in the field of modern medicine is focusing on individual differences in pathogenesis and treatment of the diseases [6]. Similarly, the concept of Mezaj (constitution) which is one of the fundamental theories of Traditional Persian Medicine (TPM), is attributed to the necessity of personalization in medicine. Mezaj which is the final average of four main qualities of hotness, coldness, wetness, and dryness helps physicians to assess deviations of body organs from their normal homeostasis and differences between individuals [7, 8].In this regard Avicenna (980-1037 AD), one of the great scholars of the Islamic Golden Age [9], believes that the normal constitution range of human’s body is completely different from animal’s. Accordingly, the effects of drugs on animals could not be extended to the humans. In the second book of his masterpiece, Canon of medicine, he asserted that one of the criteria of drug evaluation in experimental approach is that it should be tested on humans because of its different power and effect on various animal species in comparison to humans. He also gives some examples such as Chinese rhubarb (Rheum palmatum) which cause hotness in human and coldness in lion and horse, or rather some materials which are poisonous to humans in spite of their ineffectiveness in animals [10].      It seems that current evidence besides our previous knowledge shows a necessity for revision in the application of animal studies in biomedical sciences.

scholarly journals Relationship between abdominal obesity and other cardiovascular risk factors: cross sectional study of patients with symptomatic carotid disease

2013 ◽  
Vol 141 (7-8) ◽  
pp. 460-465 ◽  
Author(s):  
Milos Maksimovic ◽  
Hristina Vlajinac ◽  
Djordje Radak ◽  
Jelena Marinkovic ◽  
Jadranka Maksimovic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Abdominal Obesity ◽  
Carotid Atherosclerosis ◽  
Cross Sectional Study ◽  
Carotid Disease ◽  
Cross Sectional ◽  
Symptomatic Carotid

Introduction. Obesity, particularly visceral obesity, is considered one of major risk factors for cardiovascular events. Objectives. The aim of the present study was to investigate relationship between abdominal obesity and other cardiovascular risk factors. Methods. The cross-sectional study involved 657 consecutive patients with verified carotid atherosclerosis. Carotid atherosclerosis was estimated by high resolution B-mode ultrasonography. Abdominal obesity was defined as waist circumference >102 cm in men and >88 cm in women. Results. Abdominal obesity was present in 324 (49.3%) participants. Multivariate analyses showed that abdominal obesity was significantly positively associated with female sex, increased Baecke ?s Work Index of physical activity at work, years of school completed <12, metabolic syndrome, increased triglycerides, hyperglycemia and high serum uric acid. Smoking, alcohol consumption, physical inactivity, hypertension, increased total cholesterol, increased HDL and LDL cholesterols, increased high sensitive C-reactive protein, increased fibrinogen, anti-lipid therapy and anti-diabetic therapy were not significantly related to abdominal obesity. Conclusion. Abdominal obesity among patients with symptomatic carotid disease is significantly related to other cardiovascular risk factors, especially metabolic syndrome, metabolic syndrome components and high level of serum uric acid.

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