Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies

2007 ◽  
Vol 292 (2) ◽  
pp. C615-C640 ◽  
Author(s):  
Avraham Mayevsky ◽  
Gennady G. Rogatsky

Normal mitochondrial function is a critical factor in maintaining cellular homeostasis in various organs of the body. Due to the involvement of mitochondrial dysfunction in many pathological states, the real-time in vivo monitoring of the mitochondrial metabolic state is crucially important. This type of monitoring in animal models as well as in patients provides real-time data that can help interpret experimental results or optimize patient treatment. The goals of the present review are the following: 1) to provide an historical overview of NADH fluorescence monitoring and its physiological significance; 2) to present the solid scientific ground underlying NADH fluorescence measurements based on published materials; 3) to provide the reader with basic information on the methodologies used in the past and the current state of the art fluorometers; and 4) to clarify the various factors affecting monitored signals, including artifacts. The large numbers of publications by different groups testify to the valuable information gathered in various experimental conditions. The monitoring of NADH levels in the tissue provides the most important information on the metabolic state of the mitochondria in terms of energy production and intracellular oxygen levels. Although NADH signals are not calibrated in absolute units, their trend monitoring is important for the interpretation of physiological or pathological situations. To understand tissue function better, the multiparametric approach has been developed where NADH serves as the key parameter. The development of new light sources in UV and visible spectra has led to the development of small compact units applicable in clinical conditions for better diagnosis of patients.

2008 ◽  
Vol 01 (01) ◽  
pp. 71-83 ◽  
Author(s):  
AVRAHAM MAYEVSKY

The involvement of mitochondrial dysfunction in various pathophysiological conditions, developed in experimental and clinical situations, is widely documented. Nevertheless, real time monitoring of mitochondrial function In-vivo is very rare. The pressing question is how the mitochondria of intact tissues behave under In-vivo conditions as compared to isolated mitochondria that had been described by Chance and Williams over 50 years ago. This subject has been recently discussed in detail (Mayevsky and Rogatsky 2007). We reviewed the subject of evaluating mitochondrial function by monitoring NADH fluorescence together with microcirculatory blood flow, Hemoglobin oxygenation and tissue reflectance. These 4 parameters represent the vitality of the tissue and could be monitored in vivo, using optical spectroscopy, in animal models as well as in clinical practice. It is a well known physiological hypothesis that, under emergency conditions, the sympathetic nervous system will give preference to the most vital organs in the body, namely the brain, heart and adrenal glands. The less vital organs, such as the skin, GI-tract, and Urethral wall, will become hypoperfused and their mitochondrial activity will be inhibited. The monitoring of the less vital organs may reveal critical tissue conditions that may manifest an early phase of body deterioration. The aim of the current presentation is to review the experimental and preliminary clinical results accumulated using a new integrated medical device – the "CritiView" which enabled, for the first time, monitoring 4 parameters from the tissue using a single optical probe. The CritiView is a computerized optical device that integrates hardware and software in order to provide real time information on tissue vitality. In preliminary clinical testing, we used a 3-way Foley catheter that includes a bundle of optical fibers enabling the monitoring of the 4 parameters, representing the vitality of the urethral wall (a less vital organ).We found that the exposure of patients to metabolic imbalances in the operation room led to changes in tissue blood flow and inhibition of mitochondrial function in the urethral wall. In conclusion, the new device "CritiView" could provide reliable, real time data on mitochondrial function and tissue vitality in experimental animals as well as in patients.


2021 ◽  
Vol 10 (13) ◽  
pp. 2925
Author(s):  
Manuel Sanchez-Diaz ◽  
Maria I. Quiñones-Vico ◽  
Raquel Sanabria de la Torre ◽  
Trinidad Montero-Vílchez ◽  
Alvaro Sierra-Sánchez ◽  
...  

Mesenchymal Stromal Cells (MSCs) are of great interest in cellular therapy. Different routes of administration of MSCs have been described both in pre-clinical and clinical reports. Knowledge about the fate of the administered cells is critical for developing MSC-based therapies. The aim of this review is to describe how MSCs are distributed after injection, using different administration routes in animal models and humans. A literature search was performed in order to consider how MSCs distribute after intravenous, intraarterial, intramuscular, intraarticular and intralesional injection into both animal models and humans. Studies addressing the biodistribution of MSCs in “in vivo” animal models and humans were included. After the search, 109 articles were included in the review. Intravenous administration of MSCs is widely used; it leads to an initial accumulation of cells in the lungs with later redistribution to the liver, spleen and kidneys. Intraarterial infusion bypasses the lungs, so MSCs distribute widely throughout the rest of the body. Intramuscular, intraarticular and intradermal administration lack systemic biodistribution. Injection into various specific organs is also described. Biodistribution of MSCs in animal models and humans appears to be similar and depends on the route of administration. More studies with standardized protocols of MSC administration could be useful in order to make results homogeneous and more comparable.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 667
Author(s):  
Meera Krishnan ◽  
Sahil Kumar ◽  
Luis Johnson Kangale ◽  
Eric Ghigo ◽  
Prasad Abnave

Adult stem cells (ASCs) are the undifferentiated cells that possess self-renewal and differentiation abilities. They are present in all major organ systems of the body and are uniquely reserved there during development for tissue maintenance during homeostasis, injury, and infection. They do so by promptly modulating the dynamics of proliferation, differentiation, survival, and migration. Any imbalance in these processes may result in regeneration failure or developing cancer. Hence, the dynamics of these various behaviors of ASCs need to always be precisely controlled. Several genetic and epigenetic factors have been demonstrated to be involved in tightly regulating the proliferation, differentiation, and self-renewal of ASCs. Understanding these mechanisms is of great importance, given the role of stem cells in regenerative medicine. Investigations on various animal models have played a significant part in enriching our knowledge and giving In Vivo in-sight into such ASCs regulatory mechanisms. In this review, we have discussed the recent In Vivo studies demonstrating the role of various genetic factors in regulating dynamics of different ASCs viz. intestinal stem cells (ISCs), neural stem cells (NSCs), hematopoietic stem cells (HSCs), and epidermal stem cells (Ep-SCs).


2021 ◽  
Author(s):  
Francesca Mattedi ◽  
George Chennell ◽  
Alessio Vagnoni

Abstract Precise distribution of mitochondria is essential for maintaining neuronal homeostasis. Although detailed mechanisms governing the transport of mitochondria have emerged, it is still poorly understood how the regulation of transport is coordinated in space and time within the physiological context of an organism. How alteration in mitochondrial functionality may trigger changes in organellar dynamics also remains unclear in this context. Therefore, the use of genetically-encoded tools to perturb mitochondrial functionality in real time would be desirable. Here we describe methods to interfere with mitochondrial function with high spatiotemporal precision with the use of photosensitisers in vivo in the intact wing nerve of adult Drosophila. We also provide details on how to visualise the transport of mitochondria and to improve the quality of the imaging to attain super-resolution in this tissue.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Sai Sandeep Singh Rowdhwal ◽  
Jiaxiang Chen

Di-2-ethylhexyl phthalate (DEHP) is extensively used as a plasticizer in many products, especially medical devices, furniture materials, cosmetics, and personal care products. DEHP is noncovalently bound to plastics, and therefore, it will leach out of these products after repeated use, heating, and/or cleaning of the products. Due to the overuse of DEHP in many products, it enters and pollutes the environment through release from industrial settings and plastic waste disposal sites. DEHP can enter the body through inhalation, ingestion, and dermal contact on a daily basis, which has raised some concerns about its safety and its potential effects on human health. The main aim of this review is to give an overview of the endocrine, testicular, ovarian, neural, hepatotoxic, and cardiotoxic effects of DEHP on animal models and humansin vitroandin vivo.


The leading cause of death from the COVID-19 is the development of Pneumonia and Acute Respiratory Distress Syndrome-ARDS. Advanced physiological monitoring of COVID -19 patients in real time is a missing tool that avoid the optimization of better diagnosis and evaluating the efficacy of the treatment given. As of today, the monitoring of the systemic vital signs provides important information regarding the respiratory and cardiovascular systems including the pulse oximetry that provide data on hemoglobin oxygenation in the macro circulation. Our hypothesis is that the pathophysiology of COVID-19 and ARDS patients includes severe changes in the microcirculatory hemodynamics and cellular disturbances in Tissue and cellular Oxygen Homeostasis. Therefore, we postulate that real time monitoring of mitochondrial NADH redox state and microcirculatory blood flow, volume and hemoglobin oxygenation is the missing information that will affect dramatically the outcome of COVID-19 and ARDS patients. During the last 2 decades we studied the mechanism of blood flow redistribution activated in animal models as well as in patients exposed to total body negative oxygen balance. This mechanism is activated by the sympathetic pathway. This effect is not equal in all organs of the body, namely, in the most vital organs - brain, heart, and adrenal glands oxygen supply is preserved while in the less vital organs (visceral and peripheral organs) hypo perfusion and negative oxygen balance is recorded. In order to evaluate the tissue oxygen homeostasis, we developed a new concept named - LifenLight Score (LLS)TM based on the monitoring of four physiological parameters measured in real time from one of the less vital organs in the body. Our developed device is monitoring mitochondrial function by measuring the NADH auto fluorescence and microcirculatory blood flow, tissue reflectance and hemoglobin oxygenation. In animal model we monitored simultaneously the brain and the small intestine. In patients we used a 3-way Foley catheter introduced to the bladder via the urethra. We found that monitoring the less vital organ could serve as an early warning signal to the development of negative oxygen balance in the body as well as indicate of a recovery process in the improvement of the oxygen balance homeostasis. In conclusion, we hypothesize that using our new monitoring system will be able to detect deterioration process related to hypoxia in COVID-19 and ARDS patients, as well as to monitor improvement in tissue oxygen balance due to various treatments such as exposure to hyperoxia.


2017 ◽  
Vol 85 (11) ◽  
Author(s):  
Audrey C. Bergeron ◽  
Brittany G. Seman ◽  
John H. Hammond ◽  
Linda S. Archambault ◽  
Deborah A. Hogan ◽  
...  

ABSTRACT Polymicrobial infections often include both fungi and bacteria and can complicate patient treatment and resolution of infection. Cross-kingdom interactions among bacteria, fungi, and/or the immune system during infection can enhance or block virulence mechanisms and influence disease progression. The fungus Candida albicans and the bacterium Pseudomonas aeruginosa are coisolated in the context of polymicrobial infection at a variety of sites throughout the body, including mucosal tissues such as the lung. In vitro, C. albicans and P. aeruginosa have a bidirectional and largely antagonistic relationship. Their interactions in vivo remain poorly understood, specifically regarding host responses in mediating infection. In this study, we examine trikingdom interactions using a transparent juvenile zebrafish to model mucosal lung infection and show that C. albicans and P. aeruginosa are synergistically virulent. We find that high C. albicans burden, fungal epithelial invasion, swimbladder edema, and epithelial extrusion events serve as predictive factors for mortality in our infection model. Longitudinal analyses of fungal, bacterial, and immune dynamics during coinfection suggest that enhanced morbidity is associated with exacerbated C. albicans pathogenesis and elevated inflammation. The P. aeruginosa quorum-sensing-deficient ΔlasR mutant also enhances C. albicans pathogenicity in coinfection and induces extrusion of the swimbladder. Together, these observations suggest that C. albicans-P. aeruginosa cross talk in vivo can benefit both organisms to the detriment of the host.


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