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Deutsches Arzteblatt International Dec 2019Nearly 1000 permanent ventricular assist devices (VADs) are implanted in patients with severe congestive heart failure in Germany each year. VADs are miniaturized... (Review)
Review
BACKGROUND
Nearly 1000 permanent ventricular assist devices (VADs) are implanted in patients with severe congestive heart failure in Germany each year. VADs are miniaturized centrifugal pumps that generate continuous blood flow; they are powered and controlled through a cable that passes through the skin. Para- corporeal systems are only rarely implanted, usually in children.
METHODS
In this selective review of the literature, including guidelines and registry data, we discuss the indications, therapeutic effects, and complications of permanently implantable cardiac support systems.
RESULTS
The optimal time for VAD implantation cannot be precisely defined. A comparative assessment of the various available systems is not possible, as no randomized trials have been performed on this topic. Registry data indicate that 69% to 81% of patients survive one year after VAD implantation, which is signifi- cantly better than the natural course of (conservatively treated) severe congestive heart failure. The distance patients are able to walk is 129 to 220 m longer at six months, depending on the system implanted. Scores on the EQ-5D health status questionnaire are 28 to 37 points better at six months. The potential severe compli- cations include infection, right-heart failure, hemorrhage, pump thrombosis, stroke, and death.
CONCLUSION
A VAD system can be implanted as an alternative to cardiac transplan- tation or as a bridging treatment until the patient can be listed for transplantation and receive the transplant. Because of the organ s , only a minority of VAD patients ever receive a transplant.
Topics: Germany; Heart Failure; Heart-Assist Devices; Humans; Registries; Treatment Outcome
PubMed: 31931951
DOI: 10.3238/arztebl.2019.0843 -
Cellular Physiology and Biochemistry :... Oct 2022The functioning of complex organisms requires a constant and delicate balance of processes both between and within cells, tissues, and organ systems. There is growing... (Review)
Review
The functioning of complex organisms requires a constant and delicate balance of processes both between and within cells, tissues, and organ systems. There is growing appreciation for the role of signalling crosstalk connecting different organ systems of the body, even from tissues traditionally classified as "inert" in terms of their capacity to produce chemical signals that can act on other organ systems. Many of these secreted molecules have been shown to contribute to, or exacerbate, a variety of functions and diseases in other organ systems, even if the two organs are not functionally linked. For example, there is a strong association with skeletal muscle atrophy and dysfunction in patients with chronic kidney disease (CKD). Identification of molecules produced and secreted by skeletal muscle has existed for some time, and there is emerging evidence that skeletal muscle may directly affect kidney function. Conversely, factors produced and secreted by the kidneys in various models of CKD have been shown to contribute to reduced muscle functionality. This review will focus on crosstalk in both directions between skeletal muscle and the kidneys. The emphasis will be on direct interaction between these organs using examples of secreted factors that are produced by the muscle or kidneys (including activin A, myostatin, microRNA's, irisin and mitsugumin 53), often under pathophysiological conditions. Our understanding of how the kidneys and skeletal muscle interact with each other is key to elucidating the pathophysiology processes that drive health and disease.
Topics: Animals; Humans; Myostatin; Fibronectins; Disease Models, Animal; Muscle, Skeletal; Renal Insufficiency, Chronic; Kidney; MicroRNAs
PubMed: 36285606
DOI: 10.33594/000000578 -
Cells Nov 2021Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism's health. We propose that the... (Review)
Review
Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism's health. We propose that the age-related impairment of these systems is due to the establishment of a chronic oxidative stress situation that leads to low-grade chronic inflammation throughout the immune system's activity. It is known that the immune system weakens with age, which increases morbidity and mortality. In this context, we describe how the function of immune cells can be used as an indicator of the rate of aging of an individual. In addition to this passive role as a marker, we describe how the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging) and inducing senescence in far tissue cells. Further supporting our theory, we discuss how certain lifestyle conditions (such as social environment, nutrition, or exercise) can have an impact on longevity by affecting the oxidative and inflammatory state of immune cells, regulating immunosenescence and its contribution to oxi-inflamm-aging.
Topics: Aging; Animals; Humans; Immunosenescence; Inflammation; Leukocytes; Mitochondria; Oxidative Stress
PubMed: 34831197
DOI: 10.3390/cells10112974 -
International Journal of Molecular... May 2016Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet... (Review)
Review
Circadian rhythms, ≈24 h oscillations in behavior and physiology, are reflected in all cells of the body and function to optimize cellular functions and meet environmental challenges associated with the solar day. This multi-oscillatory network is entrained by the master pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which directs an organism's rhythmic expression of physiological functions and behavior via a hierarchical system. This system has been highly conserved throughout evolution and uses transcriptional-translational autoregulatory loops. This master clock, following environmental cues, regulates an organism's sleep pattern, body temperature, cardiac activity and blood pressure, hormone secretion, oxygen consumption and metabolic rate. Mammalian peripheral clocks and clock gene expression have recently been discovered and are present in all nucleated cells in our body. Like other essential organ of the body, the skin also has cycles that are informed by this master regulator. In addition, skin cells have peripheral clocks that can function autonomously. First described in 2000 for skin, this review summarizes some important aspects of a rapidly growing body of research in circadian and ultradian (an oscillation that repeats multiple times during a 24 h period) cutaneous rhythms, including clock mechanisms, functional manifestations, and stimuli that entrain or disrupt normal cycling. Some specific relationships between disrupted clock signaling and consequences to skin health are discussed in more depth in the other invited articles in this IJMS issue on Sleep, Circadian Rhythm and Skin.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Gene Expression; Gene Expression Regulation; Humans; Skin Physiological Phenomena; Suprachiasmatic Nucleus
PubMed: 27231897
DOI: 10.3390/ijms17060801 -
Development (Cambridge, England) Dec 2013Many organisms and their constituent tissues and organs vary substantially in size but differ little in morphology; they appear to be scaled versions of a common... (Review)
Review
Many organisms and their constituent tissues and organs vary substantially in size but differ little in morphology; they appear to be scaled versions of a common template or pattern. Such scaling involves adjusting the intrinsic scale of spatial patterns of gene expression that are set up during development to the size of the system. Identifying the mechanisms that regulate scaling of patterns at the tissue, organ and organism level during development is a longstanding challenge in biology, but recent molecular-level data and mathematical modeling have shed light on scaling mechanisms in several systems, including Drosophila and Xenopus. Here, we investigate the underlying principles needed for understanding the mechanisms that can produce scale invariance in spatial pattern formation and discuss examples of systems that scale during development.
Topics: Animals; Body Patterning; Bone Morphogenetic Proteins; Drosophila; Gene Expression Regulation, Developmental; Models, Biological; Xenopus
PubMed: 24301464
DOI: 10.1242/dev.100511 -
Cell Chemical Biology Jan 2016Organism-level systems biology aims to identify, analyze, control and design cellular circuits in organisms. Many experimental and computational approaches have been... (Review)
Review
Organism-level systems biology aims to identify, analyze, control and design cellular circuits in organisms. Many experimental and computational approaches have been developed over the years to allow us to conduct these studies. Some of the most powerful methods are based on using optical imaging in combination with fluorescent labeling, and for those one of the long-standing stumbling blocks has been tissue opacity. Recently, the solutions to this problem have started to emerge based on whole-body and whole-organ clearing techniques that employ innovative tissue-clearing chemistry. Here, we review these advancements and discuss how combining new clearing techniques with high-performing fluorescent proteins or small molecule tags, rapid volume imaging and efficient image informatics is resulting in comprehensive and quantitative organ-wide, single-cell resolution experimental data. These technologies are starting to yield information on connectivity and dynamics in cellular circuits at unprecedented resolution, and bring us closer to system-level understanding of physiology and diseases of complex mammalian systems.
Topics: Animals; Brain; Brain Mapping; Humans; Imaging, Three-Dimensional; Microscopy; Optical Imaging; Single-Cell Analysis; Systems Biology; Whole Body Imaging
PubMed: 26933741
DOI: 10.1016/j.chembiol.2015.11.009 -
Journal of Anatomy Feb 2021Organisms are inherently three dimensional, thus comprehensive understanding of the complicated biological system requires analysis of organs or even whole bodies in the... (Review)
Review
Organisms are inherently three dimensional, thus comprehensive understanding of the complicated biological system requires analysis of organs or even whole bodies in the context of three dimensions. However, this is a tremendous task since the biological specimens are naturally opaque, a major obstacle in whole-body and whole-organ imaging. Tissue clearing technique provides a prospective solution and has become a powerful tool for three-dimensional imaging and quantification of organisms. Tissue clearing technique aims to make tissue transparent by minimizing light scattering and light absorption, thus allowing deep imaging of large volume samples. When combined with diverse molecular labeling methods and high-throughput optical sectioning microscopes, tissue clearing technique enables whole-body and whole-organ imaging at cellular or subcellular resolution, providing detailed and comprehensive information about the intact biological systems. Here, we give an overview of recent progress and biomedical applications of tissue clearing technique. We introduce the mechanisms and basic principles of tissue clearing, and summarize the current tissue clearing methods. Moreover, the available imaging techniques and software packages for data processing are also presented. Finally, we introduce the recent advances in applications of tissue clearing in biomedical fields. Tissue clearing contributes to the investigation of structure-function relationships in intact mammalian organs, and opens new avenues for cellular and molecular mapping of intact human organs. We hope this review contributes to a better understanding of tissue clearing technique and can help researchers to select the best-suited clearing protocol for their experiments.
Topics: Animals; Histocytological Preparation Techniques; Humans; Imaging, Three-Dimensional; Optical Imaging
PubMed: 32939792
DOI: 10.1111/joa.13309 -
Frontiers in Physiology 2014Major evolutionary trends in animal physiology have been heavily influenced by atmospheric O2 levels. Amongst other important factors, the increase in atmospheric O2... (Review)
Review
Major evolutionary trends in animal physiology have been heavily influenced by atmospheric O2 levels. Amongst other important factors, the increase in atmospheric O2 which occurred in the Pre-Cambrian and the development of aerobic respiration beckoned the evolution of animal organ systems that were dedicated to the absorption and transportation of O2, e.g., the respiratory and cardiovascular systems of vertebrates. Global variations of O2 levels in post-Cambrian periods have also been correlated with evolutionary changes in animal physiology, especially cardiorespiratory function. Oxygen transportation systems are, in our view, ultimately controlled by the brain related mechanisms, which senses changes in O2 availability and regulates autonomic and respiratory responses that ensure the survival of the organism in the face of hypoxic challenges. In vertebrates, the major sensorial system for oxygen sensing and responding to hypoxia is the peripheral chemoreflex neuronal pathways, which includes the oxygen chemosensitive glomus cells and several brainstem regions involved in the autonomic regulation of the cardiovascular system and respiratory control. In this review we discuss the concept that regulating O2 homeostasis was one of the primordial roles of the nervous system. We also review the physiology of the peripheral chemoreflex, focusing on the integrative repercussions of chemoreflex activation and the evolutionary importance of this system, which is essential for the survival of complex organisms such as vertebrates. The contribution of hypoxia and peripheral chemoreflex for the development of diseases associated to the cardiovascular and respiratory systems is also discussed in an evolutionary context.
PubMed: 25161625
DOI: 10.3389/fphys.2014.00302 -
Experimental Biology and Medicine... Sep 2014The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical... (Review)
Review
The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ's biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different "organoids" to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology.
Topics: Animals; Brain; Drug Evaluation, Preclinical; Humans; Lab-On-A-Chip Devices; Neurogenesis; Neuronal Plasticity; Organ Culture Techniques; Rats
PubMed: 24912505
DOI: 10.1177/1535370214537738 -
Critical Reviews in Biochemistry and... Feb 2018Mutations in an organism's genome can arise spontaneously, that is, in the absence of exogenous stress and prior to selection. Mutations are often neutral or deleterious... (Review)
Review
Mutations in an organism's genome can arise spontaneously, that is, in the absence of exogenous stress and prior to selection. Mutations are often neutral or deleterious to individual fitness but can also provide genetic diversity driving evolution. Mutagenesis in bacteria contributes to the already serious and growing problem of antibiotic resistance. However, the negative impacts of spontaneous mutagenesis on human health are not limited to bacterial antibiotic resistance. Spontaneous mutations also underlie tumorigenesis and evolution of drug resistance. To better understand the causes of genetic change and how they may be manipulated in order to curb antibiotic resistance or the development of cancer, we must acquire a mechanistic understanding of the major sources of mutagenesis. Bacterial systems are particularly well-suited to studying mutagenesis because of their fast growth rate and the panoply of available experimental tools, but efforts to understand mutagenic mechanisms can be complicated by the experimental system employed. Here, we review our current understanding of mutagenic mechanisms in bacteria and describe the methods used to study mutagenesis in bacterial systems.
Topics: Animals; Bacteria; Carcinogenesis; Drug Resistance, Bacterial; Humans; Mutagenesis; Mutation; Mutation Accumulation
PubMed: 29108429
DOI: 10.1080/10409238.2017.1394262