scholarly journals Cellular mechanisms underlying steroid-resistant asthma

2019 ◽  
Vol 28 (153) ◽  
pp. 190096 ◽  
Author(s):  
Ridhima Wadhwa ◽  
Kamal Dua ◽  
Ian M. Adcock ◽  
Jay C. Horvat ◽  
Richard Y. Kim ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Experimental Studies ◽  
Therapeutic Targets ◽  
Experimental Models ◽  
Limiting Factor ◽  
Cellular Mechanisms ◽  
Steroid Resistant ◽  
Histone Deacetylase 2 ◽  
Phosphoinositide 3 Kinase ◽  
Inflammatory Phenotypes

Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.

METHODS FOR SIMULATION OF ACUTE BRAIN ISCHEMIA: PATHOPHYSIOLOGICAL SUBSTANTIATION OF SELECTION AND IMPORTANCE FOR CLINICAL PRACTICE

2019 ◽  
pp. 142-152
Author(s):  
Б.И. Гельцер ◽  
Э.В. Слабенко ◽  
Ю.В. Заяц ◽  
В.Н. Котельников
Keyword(s):  
Clinical Practice ◽  
Experimental Studies ◽  
Cerebrovascular Diseases ◽  
Experimental Models ◽  
Pathological Process ◽  
Ischemic Brain ◽  
Actual Clinical Practice ◽  
Acute Cerebral Ischemia ◽  
Different Types ◽  
Acute Brain Ischemia

Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.

scholarly journals The Nephroprotective Properties of Extracellular Vesicles in Experimental Models of Chronic Kidney Disease: a Systematic Review

2021 ◽  
Author(s):  
Natalia Nowak ◽  
Masayuki Yamanouchi ◽  
Eiichiro Satake
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Interstitial Fibrosis ◽  
Cell Damage ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Extracellular Vesicle ◽  
Experimental Models ◽  
Preclinical Research

AbstractExtracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD. Graphical Abstract

Peripheral chemoreceptors in health and disease

2004 ◽  
Vol 96 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
Ying-Jie Peng
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Defense Mechanism ◽  
Experimental Models ◽  
Cellular Mechanisms ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Oxygen Homeostasis ◽  
Arterial Blood ◽  
Carotid Bodies

Peripheral chemoreceptors (carotid and aortic bodies) detect changes in arterial blood oxygen and initiate reflexes that are important for maintaining homeostasis during hypoxemia. This mini-review summarizes the importance of peripheral chemoreceptor reflexes in various physiological and pathophysiological conditions. Carotid bodies are important for eliciting hypoxic ventilatory stimulation in humans and in experimental animals. In the absence of carotid bodies, compensatory upregulation of aortic bodies as well as other chemoreceptors contributes to the hypoxic ventilatory response. Peripheral chemoreceptors are critical for ventilatory acclimatization at high altitude. They also contribute in part to the exercise-induced hyperventilation, especially with submaximal and heavy exercise. During pregnancy, hypoxic ventilatory sensitivity increases, perhaps due to the actions of estrogen and progesterone on chemoreceptors. Augmented peripheral chemoreceptors have been implicated in early stages of recurrent apneas, congestive heart failure, and certain forms of hypertension. It is likely that chemoreceptors tend to maintain oxygen homeostasis and act as a defense mechanism to prevent the progression of the morbidity associated with these diseases. Experimental models of recurrent apneas, congestive heart failure, and hypertension offer excellent opportunities to unravel the cellular mechanisms associated with altered chemoreceptor function.

scholarly journals Mechanisms of Atrial Fibrillation – Reentry, Rotors and Reality

2014 ◽  
Vol 3 (2) ◽  
pp. 90 ◽  
Author(s):  
Jonathan W Waks ◽  
Mark E Josephson ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Catheter Ablation ◽  
20Th Century ◽  
Experimental Studies ◽  
Therapeutic Targets ◽  
Spiral Waves ◽  
Historical Understanding ◽  
New Strategies ◽  
Complex Fractionated Atrial Electrograms

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, yet our understanding of the mechanisms that initiate and sustain this arrhythmia remains quite poor. Over the last 50 years, various mechanisms of AF have been proposed, yet none has been consistently observed in both experimental studies and in humans. Recently, there has been increasing interest in understanding how spiral waves or rotors – which are specific, organised forms of functional reentry – sustain human AF and how they might be therapeutic targets for catheter-based ablation. The following review describes the historical understanding of reentry and AF mechanisms from earlier in the 20th century, advances in our understanding of mechanisms that are able to sustain AF with a focus on rotors and complex fractionated atrial electrograms (CFAEs), and how the study of AF mechanisms has resulted in new strategies for treating AF with novel forms of catheter ablation.

scholarly journals Opening the black box: Stem cell–based modeling of human post-implantation development

2018 ◽  
Vol 218 (2) ◽  
pp. 410-421 ◽  
Author(s):  
Kenichiro Taniguchi ◽  
Idse Heemskerk ◽  
Deborah L. Gumucio
Keyword(s):  
Stem Cell ◽  
Human Development ◽  
Experimental Models ◽  
Uterine Wall ◽  
Black Box ◽  
Cellular Mechanisms ◽  
Early Human Development ◽  
Post Implantation ◽  
Early Human

Proper development of the human embryo following its implantation into the uterine wall is critical for the successful continuation of pregnancy. However, the complex cellular and molecular changes that occur during this post-implantation period of human development are not amenable to study in vivo. Recently, several new embryo-like human pluripotent stem cell (hPSC)–based platforms have emerged, which are beginning to illuminate the current black box state of early human post-implantation biology. In this review, we will discuss how these experimental models are carving a way for understanding novel molecular and cellular mechanisms during early human development.

scholarly journals Experimental Modeling of Necrotizing Enterocolitis: Pathogenesis, Predictors, Prevention of the Disease

2020 ◽  
Vol 13 (3) ◽  
pp. 293-300
Author(s):  
Irina Karpova ◽  
Daria Molchanova ◽  
Tatiana Ladygina
Keyword(s):  
Necrotizing Enterocolitis ◽  
Systemic Disease ◽  
Interleukin 1 ◽  
Bacterial Flora ◽  
Experimental Studies ◽  
Experimental Models ◽  
Current Data ◽  
Experimental Modeling ◽  
Antibacterial Drug ◽  
The Impact

Introduction. The incidence rate of necrotizing enterocolitis is 2.4:1000 of newborns. The number of complications reaches 51-68%, and mortality rate varies from 4 to 80%. The aim of the study was to present current data of Russian and foreign experimental studies related to necrotizing enterocolitis in children. Results. Currently, infants with low and very low body weight constitute the most proportion of patients with enterocolitis; the development of the disease in this cohort of patients has its distinctive features. In this regard, the issues of pathogenesis, the impact of risk factors and methods of prevention of the pathological process remain underinvestigated. Experimental models were used to study the features of the toll-interleukin 1 receptor domain containing adapter protein (TIRAP), the etiology of Toll-like receptor 4 expression, and the reasons for the increased levels of inflammatory mediators. The mechanism of intestinal-brain reciprocal communication was confirmed. The role of the bacterial flora and effectiveness of the antibacterial drug effect on this flora was also determined. Biomarkers of enterocolitis, such as an epidermal growth factor, interleukins, claudins 2, 3, 4, were detected using experimental modeling. Various options for disease prevention ranging from ischemic preconditioning to probiotics application and breastfeeding were analyzed, the latter ones having beneficial ability to form natural defenses in newborns. Conclusions. Thus, necrotizing enterocolitis is a severe systemic disease. Experimental modeling allows analyzing the most complex, unsolved problems and introducing novel knowledge into clinical practice.

scholarly journals MODERN CONCEPTION AS TO THE FUNCTIONAL MORPHOLOGY OF THE OLFACTORY SYSTEM AND ITS CHANGES UNDER THE INFLUENCE OF SOME EXOGENOUS POLLUTANTS

2019 ◽  
Vol 23 (3-4) ◽  
pp. 37-40
Author(s):  
A.D. Shkodina ◽  
R.M. Hrinko ◽  
I.I. Starchenko
Keyword(s):  
Environmental Factors ◽  
Olfactory Epithelium ◽  
Functional Organization ◽  
Morphological Changes ◽  
Human Life ◽  
Experimental Studies ◽  
Experimental Models ◽  
Functional Changes ◽  
Olfactory Analyzer ◽  
Long Time

The interaction between a body and an environment provides the main aspects of human life. The study of the functional structure of the olfactory analyzer plays an important role both in clinical and in experimental studies, but the question of its features in humans needs detailed research. The paper presents the modern data of the structural and functional organization of the olfactory analyzer. Particular attention is paid to the structural organization of olfactory bulbs as most complicated and least studied component of the olfactory analyzer. The morphological and functional changes of the olfactory analyzer are developing in some diseases and in action of adverse environmental factors are described while the accentuation is placed on the differences of the mechanism in the pathogenesis of damage to the olfactory analyzer, depending on the nature of the influence of pathogenic factors. In this way as the result of short-term intense effects of the pollutant, irreversible atrophic changes are primarily affected to the olfactory epithelium, thus, to some extent, preventing the spread of the toxin to other analyzer structures. Conversely, a long-term exposure to low doses usually retains the functional activity of the olfactory epithelium, while harmful substances penetrate the central unit of the olfactory analyzer. In such cases, the olfactory dysfunction can be diagnosed after a long time after the start of the cohort with certain pollutants. Currently, studies of the influence of exogenous toxins on various parts of the olfactory analyzer on animal experimental models are quite active. At the same time, the issue of functional and morphological changes in various structural components of the human olfactory analyzer under the influence of negative environmental factors remains poorly understood and requires further morphological and biochemical studies, in order to be able to further develop effective therapeutic and prophylactic means.

scholarly journals A Narrative Review of Libidibia ferrea: Botanical Aspects, Ethnopharmacological Properties, Phytochemical Characteristics, Toxicity, and Experimental Tests

2021 ◽  
pp. 16-30
Author(s):  
Nayanne C. O. da S. Almeida ◽  
Silvania da C. Furtado ◽  
José F. M. Barcellos
Keyword(s):  
Urban Areas ◽  
Folk Medicine ◽  
Experimental Studies ◽  
Experimental Tests ◽  
Stem Bark ◽  
Experimental Models ◽  
Narrative Review ◽  
In Vivo Models ◽  
Methodological Guidelines

Introduction: Jucá or pau-ferro (Libidibia ferrea) is an arboreal plant from the Fabaceae family. It is commonly used in traditional medicine in the treatment of various diseases, including inflammatory process. Aims: The objective of this narrative review is to present botanical aspects, ethnopharmacological properties, phytochemical characteristics, toxicity highlighting, and experimental models with L. ferrea. Results: Botanical Aspects: Jucá has several uses such as in landscaping (stem and canopy), in arborization of urban areas. Ethnopharmacological Properties: It is used in the treatment of various diseases such as diabetes, flu, asthma and, inflammatory processes of which different parts are used (root, stem bark, leaves, fruits, seeds). Phytochemical Characteristics: Phenolic compounds, fatty acids, and terpenoids are among the compounds monthly used. Toxicity: In vivo models have been used to verify toxicity and in most studies the plant presented no toxicity in its use. Experimental studies: Animals, such as mice, dogs, rats, etc. and different models of studies to analyze the action of the plant were used. Conclusions: Such low toxicity, associated with its widespread use in folk medicine and its various effects demonstrated in the studies included in this Review have corroborated for the continuity of the research with L. ferrea. New studies, however, ought to follow methodological guidelines, such as the Animal Research: reporting in vivo Experiments (ARRIVE) so that, a methodological design secures more homogeneous studies capable of quantifying the actual size of the effect in the plant may have in clinical studies.  

scholarly journals Gaseous neurotransmitter nitric oxide: Its role in experimental models of epilepsy

2012 ◽  
Vol 64 (3) ◽  
pp. 1207-1216 ◽  
Author(s):  
D. Hrncic ◽  
Aleksandra Rasic-Markovic ◽  
Jelica Bjekic-Macut ◽  
Veselinka Susic ◽  
D. Mladenovic ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Experimental Studies ◽  
Experimental Models ◽  
Initiation And Propagation ◽  
Organ Systems ◽  
The Central Nervous System ◽  
Animal Models Of Epilepsy ◽  
Almost All ◽  
Gaseous Neurotransmitter ◽  
Models Of Epilepsy

Epilepsy is one of the leading neurological disorders and affects 1-2% of the world?s population. Generally, it is a result of an imbalance between excitatory and inhibitory phenomena in the central nervous system (CNS), but the mechanisms of its initiation and propagation still require further investigations. Experimental models represent one of the most powerful tools to better understand the mechanisms of epileptogenesis. Nitric oxide (NO) is gaseous molecule with pleiotropic physiological and pathological effects in almost all organ systems and intriguing biological relevance, especially in the CNS where it acts as a gaseous neurotransmitter. The role of NO in the generation of epilepsy is highly contradictory, since there is evidence of its anticonvulsive, as well as proconvulsive properties. Therefore, we will discuss in this review the involvement of NO-mediated signaling pathways in the mechanisms of epileptogenesis, taking into account the findings revealed in experimental studies on animal models of epilepsy.

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