Mechanisms of Bone Remodeling Disorder in Hemophilia

2020 ◽  
Author(s):  
Hanshi Wang ◽  
Xizhuang Bai
Keyword(s):  
Bone Remodeling ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Factor Ix ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
Increased Risk ◽  
Prevention Of Osteoporosis ◽  
Antihemophilic Factor ◽  
Shed Light

AbstractHemophilia is caused by a lack of antihemophilic factor(s), for example, factor VIII (FVIII; hemophilia A) and factor IX (FIX; hemophilia B). Low bone mass is widely reported in epidemiological studies of hemophilia, and patients with hemophilia are at an increased risk of fracture. The detailed etiology of bone homeostasis imbalance in hemophilia is unclear. Clinical and experimental studies show that FVIII and FIX are involved in bone remodeling. However, it is likely that antihemophilic factors affect bone biology through thrombin pathways rather than via their own intrinsic properties. In addition, among patients with hemophilia, there are pathophysiological processes in several systems that might contribute to bone loss. This review summarizes studies on the association between hemophilia and bone remodeling, and might shed light on the challenges facing the care and prevention of osteoporosis and fracture in patients with hemophilia.

scholarly journals Upstream Treatment of Atrial Fibrillation with n-3 Polyunsaturated Fatty Acids: Myth or Reality?

2015 ◽  
Vol 4 (3) ◽  
pp. 163 ◽  
Author(s):  
Francesco Orso ◽  
Gianna Fabbri ◽  
Aldo Pietro Maggioni ◽  
◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Cardiac Electrophysiology ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Clinical Settings ◽  
Increased Risk ◽  
History Of ◽  
Af Recurrence

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and is associated with an increased risk of fatal and non-fatal events. Antiarrhythmic drugs provide limited protection against AF recurrence and have a poor safety profile. Several mechanisms have been proven to be involved in AF, e.g. inflammation, oxidative stress, fibrosis and ischaemia. Prevention of AF with interventions that target these mechanisms has emerged as a result of experimental studies suggesting the use of upstream therapies. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) have multiple effects on cardiac electrophysiology, and epidemiological studies on fish oil suggest a possible use of n-3 PUFA in AF prevention. Several randomised clinical trials have been designed to evaluate the efficacy of n-3 PUFA in preventing AF. In this review, we report the conflicting results of these trials in two different clinical settings: recurrence in patients with history of AF and development of post-operative AF in patient undergoing cardiac surgery.

scholarly journals Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Rinaldo Florencio-Silva ◽  
Gisela Rodrigues da Silva Sasso ◽  
Estela Sasso-Cerri ◽  
Manuel Jesus Simões ◽  
Paulo Sérgio Cerri
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Current Data ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
Structure And Functions

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

Mechanisms and dose-response relationships for radiation-induced cardiovascular disease

2012 ◽  
Vol 41 (3-4) ◽  
pp. 72-79 ◽  
Author(s):  
F.A. Stewart
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Experimental Studies ◽  
Cardiovascular Effects ◽  
Myocardial Cell ◽  
Epidemiological Studies ◽  
Thoracic Irradiation ◽  
Cell Immunity ◽  
Increased Risk ◽  
Elevated Cholesterol

Epidemiological studies have shown a clear association between therapeutic doses of thoracic irradiation and increased risk of cardiovascular disease in long-term cancer survivors. Survivors of Hodgkin's lymphoma and childhood cancers, for example, show 2- to >7-fold increases in risk of cardiac death after total tumour doses of 30–40 Gy, given in 2-Gy fractions. The risk of cardiac mortality increases linearly with dose, although there are large uncertainties for mean cardiac doses <5 Gy. Experimental studies show that doses of ⩾2 Gy induce the expression of inflammatory and thrombotic molecules in endothelial cells. In the heart, this causes progressive loss of capillaries and eventually leads to reduced perfusion, myocardial cell death, and fibrosis. In large arteries, doses of ⩾8 Gy, combined with elevated cholesterol, initiates atherosclerosis and predisposes to the formation of inflammatory, unstable lesions, which are prone to rupture and may cause a fatal heart attack or stroke. In contrast, doses <1 Gy inhibit inflammatory cell adhesion to endothelial cells and inhibit the development of atherosclerosis in mice. It seems likely that mechanisms other than accelerated atherosclerosis are responsible for cardiovascular effects after low total-body exposures of radiation (e.g. impaired T-cell immunity or persistent increase in systemic cytokines).

scholarly journals Interactions of nanoparticles with pulmonary structures and cellular responses

2008 ◽  
Vol 294 (5) ◽  
pp. L817-L829 ◽  
Author(s):  
Christian Mühlfeld ◽  
Barbara Rothen-Rutishauser ◽  
Fabian Blank ◽  
Dimitri Vanhecke ◽  
Matthias Ochs ◽  
...  
Keyword(s):  
Inhalation Exposure ◽  
Experimental Studies ◽  
Cellular Responses ◽  
Epidemiological Studies ◽  
Oxygen Species ◽  
Adverse Health Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
Dose Metrics ◽  
Methodological Problems ◽  
Shed Light

Combustion-derived and synthetic nano-sized particles (NSP) have gained considerable interest among pulmonary researchers and clinicians for two main reasons. 1) Inhalation exposure to combustion-derived NSP was associated with increased pulmonary and cardiovascular morbidity and mortality as suggested by epidemiological studies. Experimental evidence has provided a mechanistic picture of the adverse health effects associated with inhalation of combustion-derived and synthetic NSP. 2) The toxicological potential of NSP contrasts with the potential application of synthetic NSP in technological as well as medicinal settings, with the latter including the use of NSP as diagnostics or therapeutics. To shed light on this paradox, this article aims to highlight recent findings about the interaction of inhaled NSP with the structures of the respiratory tract including surfactant, alveolar macrophages, and epithelial cells. Cellular responses to NSP exposure include the generation of reactive oxygen species and the induction of an inflammatory response. Furthermore, this review places special emphasis on methodological differences between experimental studies and the caveats associated with the dose metrics and points out ways to overcome inherent methodological problems.

scholarly journals Cardiovascular Disease, Aging, and Clonal Hematopoiesis

2020 ◽  
Vol 15 (1) ◽  
pp. 419-438 ◽  
Author(s):  
Megan A. Evans ◽  
Soichi Sano ◽  
Kenneth Walsh
Keyword(s):  
Cardiovascular Disease ◽  
Somatic Mutations ◽  
Mutant Cell ◽  
Experimental Studies ◽  
The Elderly ◽  
Epidemiological Studies ◽  
Clonal Hematopoiesis ◽  
Traditional Risk Factors ◽  
The Relationship ◽  
Shed Light

Traditional risk factors are incompletely predictive of cardiovascular disease development, a leading cause of death in the elderly. Recent epidemiological studies have shown that human aging is associated with an increased frequency of somatic mutations in the hematopoietic system, which provide a competitive advantage to a mutant cell, thus allowing for its clonal expansion, a phenomenon known as clonal hematopoiesis. Unexpectedly, these mutations have been associated with a higher incidence of cardiovascular disease, suggesting a previously unrecognized connection between somatic mutations in hematopoietic cells and cardiovascular disease. Here, we provide an up-to-date review of clonal hematopoiesis and its association with aging and cardiovascular disease. We also give a detailed report of the experimental studies that have been instrumental in understanding the relationship between clonal hematopoiesis and cardiovascular disease and have shed light on the mechanisms by which hematopoietic somatic mutations contribute to disease pathology.

Sex-dependent effect of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults

2020 ◽  
pp. 1-8
Author(s):  
B. Ostadal ◽  
I. Ostadalova ◽  
O. Szarszoi ◽  
I. Netuka ◽  
V. Olejnickova ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Heart Defects ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Oxygen Deprivation ◽  
Dependent Manner ◽  
Perinatal Hypoxia ◽  
Adult Males ◽  
Increased Risk

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

scholarly journals Opium Carcinogenicity: A Systematic Review of Experimental Studies

2021 ◽  
Author(s):  
Haniyeh Rafipour ◽  
Elham Mohebbi ◽  
Kazem Zendehdel ◽  
Samad Muhammadnejad ◽  
Paria Akbari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Complex Composition ◽  
Increased Risk ◽  
Modern Genomic ◽  
Opium Use

Several epidemiological studies have reported that regular use of opium can be associated with an increased risk of developing cancers, including oesophageal, laryngeal, bladder, lung, and gastric cancer. In this systematic review, we aimed at investigating whether experimental studies support this finding and, if yes, how opium consumption can cause cancer. Most of the articles that have studied opium or its derivatives have found it as a carcinogen. However, due to the complex composition, different forms, and various ways of opium use, further comprehensive experimental studies are required. Using modern genomic and epigenomic methods seems to help determine the molecular mechanisms underlying opium carcinogenicity.

Pathogens and atherosclerosis: Update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis

2011 ◽  
Vol 106 (11) ◽  
pp. 858-867 ◽  
Author(s):  
Lee Ann Campbell ◽  
Michael Rosenfeld
Keyword(s):  
Cardiovascular Disease ◽  
Influenza A ◽  
Chlamydia Pneumoniae ◽  
Acute Phase Proteins ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Potential Contribution ◽  
Infectious Agents ◽  
Or Groups ◽  
Increased Risk

SummaryIt is currently unclear what causes the chronic inflammation within atherosclerotic plaques. One emerging paradigm suggests that infection with bacteria and/or viruses can contribute to the pathogenesis of atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at non-vascular sites. This paradigm has been supported by multiple epidemiological studies that have established positive associations between the risk of cardiovascular disease morbidity and mortality and markers of infection. It has also been supported by experimental studies showing an acceleration of the development of atherosclerosis following infection of hyperlipidaemic animal models. There are now a large number of different infectious agents that have been linked with an increased risk of cardiovascular disease. These include: Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori, influenza A virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. However, there are significant differences in the strength of the data supporting their association with cardiovascular disease pathogenesis. In some cases, the infectious agents are found within the plaques and viable organisms can be isolated suggesting a direct effect. In other cases, the association is entirely based on biomarkers. In the following review, we evaluate the strength of the data for individual or groups of pathogens with regard to atherosclerosis pathogenesis and their potential contribution by direct or indirect mechanisms and discuss whether the established associations are supportive of the infectious disease paradigm. We also discuss the failure of antibiotic trials and the question of persistent infection.

scholarly journals Linking type 2 diabetes and gynecological cancer: an introductory overview

2018 ◽  
Vol 56 (9) ◽  
pp. 1413-1425 ◽  
Author(s):  
Emanuela Anastasi ◽  
Tiziana Filardi ◽  
Sara Tartaglione ◽  
Andrea Lenzi ◽  
Antonio Angeloni ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gynecological Cancer ◽  
Gynecologic Cancer ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Introductory Overview ◽  
Increased Risk ◽  
Gynecologic Neoplasms ◽  
Correct Understanding

Abstract Type 2 diabetes (T2D) is a chronic disease with a growing prevalence and a leading cause of death in many countries. Several epidemiological studies observed an association between T2D and increased risk of many types of cancer, such as gynecologic neoplasms (endometrial, cervical, ovarian and vulvar cancer). Insulin resistance, chronic inflammation and high free ovarian steroid hormones are considered the possible mechanisms behind this complex relationship. A higher risk of endometrial cancer was observed in T2D, even though this association largely attenuated after adjusting for obesity. A clear relationship between the incidence of cervical cancer (CC) and T2D has still not be determined; however T2D might have an impact on prognosis in patients with CC. To date, studies on the association between T2D and ovarian cancer (OC) are limited. The effect of pre-existing diabetes on cancer-specific mortality has been evaluated in several studies, with less clear results. Other epidemiological and experimental studies focused on the potential role of diabetes medications, mainly metformin, in cancer development in women. The correct understanding of the link between T2D and gynecologic cancer risk and mortality is currently imperative to possibly modify screening and diagnostic-therapeutic protocols in the future.

scholarly journals Environmental factors and breast cancer

Medicina ◽  
2010 ◽  
Vol 46 (12) ◽  
pp. 867 ◽  
Author(s):  
Loreta Strumylaitė ◽  
Kristina Mechonošina ◽  
Šarūnas Tamašauskas
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Environmental Factors ◽  
Cancer Risk ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Breast Cancer Cell Lines ◽  
Increased Risk ◽  
Reproductive Life

This review summarizes the results of studies on the effects of environment on breast cancer risk. As known risk factors such as reproductive life, inheritance, and socioeconomic status are estimated to explain only about half of the breast cancer cases, it has been thought that environmental factors could also be related to the risk of this disease. It is known that ionizing radiation is an environmental risk factor increasing the risk of breast cancer. The data of experimental studies show that some organochlorines could be associated with breast cancer risk although the data from epidemiological studies are not consistent due to the difficulties to assess exposure and other risk factors. Recent experimental studies show that cadmium is an environmental factor that mimics the effects of estradiol in estrogen-responsive breast cancer cell lines while solar radiation possibly decreases the risk due to protective effect of vitamin D. The data on the effect of electromagnetic fields are not consistent. Although evidence about the effect of environmental factors on the risk of breast cancer is not convincing, some of these factors together with inheritance, reproductive life, and age at exposure could be associated with an increased risk of the disease.

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