scholarly journals What Can Chemical Carcinogenesis Shed Light on the LNT Hypothesis in Radiation Carcinogenesis?

Dose-Response ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155932581987679
Author(s):  
James E. Trosko
Keyword(s):  
Chemical Carcinogenesis ◽  
Epidemiological Studies ◽  
Invasion And Metastasis ◽  
Radiation Carcinogenesis ◽  
Scientifically Based Research ◽  
Physical Chemical ◽  
Microbiological Agents ◽  
Promotion Process ◽  
Shed Light ◽  
Lnt Model

To protect the public’s health from exposure to physical, chemical, and microbiological agents, it is important that any policy be based on rigorous scientifically based research. The concept of “linear no-threshold” (LNT) has been implemented to provide guideline exposures to these agents. The practical limitation to testing this hypothesis is to provide sufficient samples for experimental or epidemiological studies. While there is no universally accepted understanding of most human diseases, there seems to be better understanding of cancer that might help resolve the “LNT” model. The public’s concern, after being exposed to radiation, is the potential of producing cancer. The most rigorous hypothesis of human carcinogenesis is the “multistage, multimechanism” chemical carcinogenesis model. The radiation carcinogenesis LNT model, rarely, if ever, built it into their support. It will be argued that this multistage, multimechanism model of carcinogenesis, involving the “initiation” of a single cell by a mutagen event, followed by chronic exposure to threshold levels of epigenetic agents or conditions that stimulate the clonal expansion of the “initiated” cell, can convert these benign cells to become invasive and metastatic. This “promotion” process can be interrupted, thereby preventing these initiated cells from transitioning to the “progression” process of invasion and metastasis.

scholarly journals Chemical carcinogenesis

2007 ◽  
Vol 79 (4) ◽  
pp. 593-616 ◽  
Author(s):  
Paula A. Oliveira ◽  
Aura Colaço ◽  
Raquel Chaves ◽  
Henrique Guedes-Pinto ◽  
Luis F. De-La-Cruz P. ◽  
...  
Keyword(s):  
Control Cell ◽  
Chemical Compounds ◽  
Chemical Carcinogenesis ◽  
Epidemiological Studies ◽  
Laboratory Animals ◽  
Epigenetic Alterations ◽  
Effective Strategies ◽  
Genetic Modifications ◽  
Gradual Process ◽  
Three Stages

The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair - i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.

scholarly journals Beyond the State of the Art: Novel Approaches for Thermal and Electrical Transport in Nanoscale Devices

Entropy ◽  
2019 ◽  
Vol 21 (8) ◽  
pp. 752 ◽  
Author(s):  
Robert Biele ◽  
Roberto D’Agosta
Keyword(s):  
Electrical Transport ◽  
State Of The Art ◽  
Biological Effects ◽  
The State ◽  
Nanoscale Devices ◽  
Natural Processes ◽  
Physical Chemical ◽  
Novel Approaches ◽  
Shed Light ◽  
Spin Momentum

Almost any interaction between two physical entities can be described through the transfer of either charge, spin, momentum, or energy. Therefore, any theory able to describe these transport phenomena can shed light on a variety of physical, chemical, and biological effects, enriching our understanding of complex, yet fundamental, natural processes, e.g., catalysis or photosynthesis. In this review, we will discuss the standard workhorses for transport in nanoscale devices, namely Boltzmann’s equation and Landauer’s approach. We will emphasize their strengths, but also analyze their limits, proposing theories and models useful to go beyond the state of the art in the investigation of transport in nanoscale devices.

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.

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 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.

scholarly journals Micromolar Valproic Acid Doses Preserve Survival and Induce Molecular Alterations in Neurodevelopmental Genes in Two Strains of Zebrafish Larvae

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1364
Author(s):  
Andrea Messina ◽  
Alessandra Boiti ◽  
Valeria Anna Sovrano ◽  
Paola Sgadò
Keyword(s):  
Valproic Acid ◽  
Epidemiological Studies ◽  
Autism Spectrum ◽  
Embryo Survival ◽  
Molecular Alterations ◽  
Zebrafish Larvae ◽  
Embryonic Exposure ◽  
Anxiety Behavior ◽  
Spectrum Disorders ◽  
Shed Light

Autism spectrum disorders (ASDs) comprise a genetically heterogeneous group of conditions characterized by a multifaceted range of impairments and multifactorial etiology. Epidemiological studies have identified valproic acid (VPA), an anticonvulsant used to treat epilepsy, as an environmental factor for ASDs. Based on these observations, studies using embryonic exposure to VPA have been conducted in many vertebrate species to model ASD. The zebrafish is emerging as a popular model in biomedical research to study the molecular pathways involved in nervous system disorders. VPA exposure in zebrafish larvae has been shown to produce a plethora of effects on social, motor and anxiety behavior, and several genetic pathways altered by VPA have been described. However, the doses and regimen of administration reported in the literature are very heterogenous, creating contradictory results and posing serious limits to the interpretation of VPA action on neurodevelopment. To shed light on the toxic effect of VPA, we tested micromolar concentrations of VPA, using exposure for 24 and 48 h in two different zebrafish strains. Our results show that micromolar doses of VPA mildly affect embryo survival but are sufficient to induce molecular alterations in neurodevelopmental genes previously shown to be influenced by VPA, with substantial differences between strains.

scholarly journals Epidemiological profile of orthopedics and traumatology patients in Palmas, Tocantins, Brazil

2021 ◽  
Vol 43 ◽  
pp. e54797
Author(s):  
Ediana Vasconcelos da Silva ◽  
Kércio Jeaneryson Nogueira de Sousa Leite ◽  
Roqueline Ametila e Gloria Martins de Freitas Aversi-Ferreira ◽  
Tales Alexandre Aversi-Ferreira
Keyword(s):  
Primary Care ◽  
Health Promotion ◽  
Health Professionals ◽  
Vertebral Column ◽  
Epidemiological Studies ◽  
National Plan ◽  
General Picture ◽  
Treatment Plans ◽  
Epidemiological Profile ◽  
Promotion Process

Epidemiological studies, both in general and specifically, are part of the health promotion process and prophylactic actions that can generate treatment plans for a population, however, the accomplishment of prophylactic work in relation to musculoskeletal (i.e., traumatological) problems must start from the specific and go to the general, from cities to a national plan, since each population has its own characteristics in the general picture of conditions. Hypothetically, the epidemiological profile in traumatology and orthopedics, due to the general behavior in the national territory, presents the lack of prevention; in this way, is necessary to verify. This work aims to determine the incidence of orthopedic and traumatological problems in the region of Palmas, state of Tocantins (TO), Brazil, in order to contribute to a possible prophylactic plan for the population of the region. The data of the present study agree with most other studies about the orthopedic profile in terms of gender, age and problems with vertebral column, in general. However, the finding that most of the conditions were associated with scoliosis was unexpected, as it differs from the findings of most studies. It was possible to establish a profile of patients seen at the clinic-school and indicate the management of training for health professionals related to the treatment of people over the age of 40 years. The importance of the action of physiotherapists in the processes of prevention and primary care was evident given the patients indicated in this and other articles who need help with traumatic diseases.

scholarly journals Chronic circadian disruption modulates breast cancer cell stemness and their immune microenvironment to drive metastasis in mice

2019 ◽  
Author(s):  
Eva Hadadi ◽  
William Taylor ◽  
Xiaomei Li ◽  
Yetki Aslan ◽  
Marthe Villote ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Night Shift ◽  
Mammary Tumorigenesis ◽  
Tumour Microenvironment ◽  
Epidemiological Studies ◽  
Circadian Disruption ◽  
Cell Dissemination ◽  
Shed Light

AbstractBreast cancer is the most common type and one of the major causes of cancer death in woman worldwide. Epidemiological studies have established a link between night shift work and increased cancer risk, suggesting that circadian disruption may interfere with carcinogenesis. We aim to shed light on the effect of chronic jetlag on mammary tumour development. Therefore, we used a mouse model of spontaneous mammary tumorigenesis that we exposed to chronic circadian disruption. We observed that circadian disruption significantly increases cancer cell dissemination and metastasis. It also enhances the stemness and tumour–initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. We finally showed that all these defects can be corrected by the use of a CXCR2 inhibitor. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.

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