scholarly journals The impact of endocrine disruptors on oocyte competence

Reproduction ◽  
2003 ◽  
pp. 313-325 ◽  
Author(s):  
P Pocar ◽  
TA Brevini ◽  
B Fischer ◽  
F Gandolfi
Keyword(s):  
Endocrine Disruptors ◽  
In Vitro Models ◽  
Environmental Chemicals ◽  
Farm Animals ◽  
Published Data ◽  
Environmental Matrices ◽  
Oocyte Competence ◽  
Natural Hormone ◽  
The Impact

To date, approximately 60 chemicals have been identified as endocrine disruptors: exogenous agents that interfere with various aspects of natural hormone physiology. The potential reproductive and health hazards of these environmental chemicals have recently generated concern among the scientific community, policy makers and general public. The present review presents and discusses the available evidence that environmental chemicals are causing ovarian toxicity in various species, with particular attention to farm animals. The impact of chronic exposure to endocrine disruptors via food and drinking water cannot be neglected when studying fertility problems in these species. This review focuses attention on the superfamily of organochlorine chemicals, persistent organic pollutants (POPs), because of their persistence in the environment, ability to concentrate up the food chain, continued detection in environmental matrices and ability to be stored in the adipose tissue of animals and humans. Published data clearly indicate that POPs disrupt mammalian oocyte maturation and follicle physiology in every species studied so far, including farm animals. However, as most of the data available still derive from experiments performed on laboratory species or in vitro models, great care should be taken when extrapolations to other species or environmental situations are attempted.

scholarly journals Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1167
Author(s):  
Marina Campos-Valdez ◽  
Hugo C. Monroy-Ramírez ◽  
Juan Armendáriz-Borunda ◽  
Laura V. Sánchez-Orozco
Keyword(s):  
Hepatitis B ◽  
Molecular Mechanisms ◽  
Time Lapse ◽  
In Vitro Models ◽  
Acute Stage ◽  
Hbv Infection ◽  
Published Data ◽  
Hepatitis B Infection ◽  
The Impact

The immunopathogenesis and molecular mechanisms involved during a hepatitis B virus (HBV) infection have made the approaches for research complex, especially concerning the patients’ responses in the course of the early acute stage. The study of molecular bases involved in the viral clearance or persistence of the infection is complicated due to the difficulty to detect patients at the most adequate points of the disease, especially in the time lapse between the onset of the infection and the viral emergence. Despite this, there is valuable data obtained from animal and in vitro models, which have helped to clarify some aspects of the early immune response against HBV infection. The diversity of the HBV (genotypes and variants) has been proven to be associated not only with the development and outcome of the disease but also with the response to treatments. That is why factors involved in the virus evolution need to be considered while studying hepatitis B infection. This review brings together some of the published data to try to explain the immunological and molecular mechanisms involved in the different stages of the infection, clinical outcomes, viral persistence, and the impact of the variants of HBV in these processes.

scholarly journals Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

2021 ◽  
Vol 22 (15) ◽  
pp. 7929
Author(s):  
Megan Chesnut ◽  
Thomas Hartung ◽  
Helena Hogberg ◽  
David Pamies
Keyword(s):  
Large Scale ◽  
In Vitro Models ◽  
Environmental Chemicals ◽  
Developmental Neurotoxicity ◽  
In Vivo Studies ◽  
Regulatory Guidelines ◽  
In Vitro Systems ◽  
Human Oligodendrocytes

Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential. Myelination is a fundamental process in neurodevelopment that should be included in a DNT testing strategy, but there are very few in vitro models of myelination. Thus, there is a need to establish an in vitro myelination assay for DNT. Here, we summarize the routes of myelin toxicity and the known models to study this particular endpoint.

scholarly journals Isolation and structural elucidation of dimeric epigallocatechin-3-gallate autoxidation products and their antioxidant capacity

2021 ◽  
Author(s):  
Julian Alfke ◽  
Uta Kampermann ◽  
Svetlana Kalinina ◽  
Melanie Esselen
Keyword(s):  
Antioxidant Capacity ◽  
Antioxidant Properties ◽  
Cd Spectroscopy ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Published Data ◽  
Dietary Polyphenols ◽  
Cellular Effects ◽  
The Impact

AbstractDietary polyphenols like epigallocatechin-3-gallate (EGCG)—which represents the most abundant flavan-3-ol in green tea—are subject of several studies regarding their bioactivity and health-related properties. On many occasions, cell culture or in vitro experiments form the basis of published data. Although the stability of these compounds is observed to be low, many reported effects are directly related to the parent compounds whereas the impact of EGCG degradation and autoxidation products is not yet understood and merely studied. EGCG autoxidation products like its dimers theasinensin A and D, “P2” and oolongtheanin are yet to be characterized in the same extent as their parental polyphenol. However, to investigate the bioactivity of autoxidation products—which would minimize the discrepancy between in vitro and in vivo data—isolation and structure elucidation techniques are urgently needed. In this study, a new protocol to acquire the dimers theasinensin A and D as well as oolongtheanin is depicted, including a variety of spectroscopic and quadrupole time-of-flight high-resolution mass spectrometric (qTOF-HRMS) data to characterize and assign these isolates. Through nuclear magnetic resonance (NMR) spectroscopy, polarimetry, and especially circular dichroism (CD) spectroscopy after enzymatic hydrolysis the complementary atropisomeric stereochemistry of the isolated theasinensins is illuminated and elucidated. Lastly, a direct comparison between the isolated EGCG autoxidation products and the monomer itself is carried out regarding their antioxidant properties featuring Trolox equivalent antioxidant capacity (TEAC) values. These findings help to characterize these products regarding their cellular effects and—which is of special interest in the flavonoid group—their redox properties.

scholarly journals Are In Vitro Susceptibilities to Azole Antifungals Predictive of Clinical Outcome in the Treatment of Candidemia?

2018 ◽  
Vol 56 (12) ◽  
Author(s):  
Twisha S. Patel ◽  
Peggy L. Carver ◽  
Gregory A. Eschenauer
Keyword(s):  
Invasive Candidiasis ◽  
Randomized Trials ◽  
Published Data ◽  
Murine Models ◽  
Limited Data ◽  
Content Type ◽  
Clinical Breakpoints ◽  
The Impact ◽  
The Relationship

ABSTRACT The purpose of this review is to critically analyze published data evaluating the impact of azole pharmacokinetic and pharmacodynamic parameters, MICs, and Candida species on clinical outcomes in patients with candidemia. Clinical breakpoints (CBPs) for fluconazole and voriconazole, which are used to determine susceptibility, have been defined by the Clinical and Laboratory Standards Institute (CLSI) for Candida species. Studies evaluating the relationship between treatment efficacy and in vitro susceptibility, as well as the pharmacodynamic targets, have been conducted in patients treated with fluconazole for candidemia; however, for species other than Candida albicans and Candida glabrata, and for other forms of invasive candidiasis, data remain limited and randomized trials are not available. Limited data evaluating these relationships with voriconazole are available. While pharmacodynamic targets for posaconazole and isavuconazole have been proposed based upon studies conducted in murine models, CBPs have not been established by CLSI. Fluconazole remains an important antifungal agent for the treatment of candidemia, and data supporting its use based on in vitro susceptibility are growing, particularly for C. albicans and C. glabrata. Further investigation is needed to establish the roles of voriconazole, posaconazole, and isavuconazole in the treatment of candidemia and for all agents in the treatment of other forms of invasive candidiasis.

scholarly journals Human iPSC-Derived Glia as a Tool for Neuropsychiatric Research and Drug Development

2021 ◽  
Vol 22 (19) ◽  
pp. 10254
Author(s):  
Johanna Heider ◽  
Sabrina Vogel ◽  
Hansjürgen Volkmer ◽  
Ricarda Breitmeyer
Keyword(s):  
Drug Development ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
In Vitro Models ◽  
Neuropsychiatric Diseases ◽  
Culture Models ◽  
Target Screening ◽  
Induced Pluripotent ◽  
The Impact

Neuropsychiatric disorders such as schizophrenia or autism spectrum disorder represent a leading and growing burden on worldwide mental health. Fundamental lack in understanding the underlying pathobiology compromises efficient drug development despite the immense medical need. So far, antipsychotic drugs reduce symptom severity and enhance quality of life, but there is no cure available. On the molecular level, schizophrenia and autism spectrum disorders correlate with compromised neuronal phenotypes. There is increasing evidence that aberrant neuroinflammatory responses of glial cells account for synaptic pathologies through deregulated communication and reciprocal modulation. Consequently, microglia and astrocytes emerge as central targets for anti-inflammatory treatment to preserve organization and homeostasis of the central nervous system. Studying the impact of neuroinflammation in the context of neuropsychiatric disorders is, however, limited by the lack of relevant human cellular test systems that are able to represent the dynamic cellular processes and molecular changes observed in human tissue. Today, patient-derived induced pluripotent stem cells offer the opportunity to study neuroinflammatory mechanisms in vitro that comprise the genetic background of affected patients. In this review, we summarize the major findings of iPSC-based microglia and astrocyte research in the context of neuropsychiatric diseases and highlight the benefit of 2D and 3D co-culture models for the generation of efficient in vitro models for target screening and drug development.

scholarly journals Effects of Saliva From Periodontally Healthy and Diseased Subjects on Barrier Function and the Inflammatory Response in in vitro Models of the Oral Epithelium

2022 ◽  
Vol 2 ◽  
Author(s):  
Antoine Roy ◽  
Amel Ben Lagha ◽  
Reginaldo Gonçalves ◽  
Daniel Grenier
Keyword(s):  
Inflammatory Response ◽  
Matrix Metalloproteinase ◽  
Barrier Function ◽  
Chronic Inflammatory Disease ◽  
In Vitro Models ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Epithelium ◽  
Chemokine Ligand ◽  
The Impact

Background: Periodontitis is a multifactorial, bacteria-mediated chronic inflammatory disease that results in the progressive destruction of the tooth-supporting tissues. It is well-known that saliva from subjects suffering from this disease generally contains higher levels of pro-inflammatory mediators, matrix metalloproteinases (MMP), and bacteria-derived toxic products. The aim of this study was to investigate and compare the effects of saliva from periodontally healthy and diseased subjects on the barrier function and inflammatory response in in vitro models of the oral epithelium.Methods: Unstimulated saliva samples from two groups of subjects, one with a healthy periodontium (n = 12) and one with severe generalized periodontitis (n = 11), were filter-sterilized. All the saliva samples were analyzed using an immunological multiplex assay to determine the levels of various cytokines and MMPs relevant to periodontitis. The impact of saliva on epithelial barrier integrity was assessed by monitoring transepithelial electrical resistance (TER) in an oral epithelium model using the B11 keratinocyte cell line. GMSM-K oral epithelial cells were treated with saliva from both groups to determine their ability to induce the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8), as determined by an enzyme-linked immunosorbent assay (ELISA).Results: Saliva from the periodontitis subjects contained significantly higher concentrations of matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), IL-8, and C-X-C motif chemokine ligand 1 (CXCL1) compared to saliva from the healthy subjects. Saliva from the healthy and periodontitis subjects affected cytokine secretion and TER in a similar manner. More specifically, saliva from both groups increased TER and induced IL-6 and IL-8 secretion in the in vitro oral epithelium models used.Conclusion: Independently of the presence or absence of periodontitis, saliva can increase the relative TER and the secretion of IL-6 and IL-8 in in vitro models of the oral epithelium.

IN VITRO MODELS OF MYCOBACTERIUM TUBERCULOSIS DORMANCY, AND IN VIVO MODELS OF LATENT TUBERCULOSIS INFECTION

2019 ◽  
Vol 64 (5) ◽  
pp. 299-307
Author(s):  
M. V. Fursov ◽  
I. A. Dyatlov ◽  
V. D. Potapov
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
In Vitro Models ◽  
Tuberculosis Infection ◽  
Published Data ◽  
In Vivo Models ◽  
Dormant State

Modeling of tuberculosis infection is carried out in order to clarify various aspects of the tuberculosis pathogenesis, as well as the testing of new anti-tuberculosis drugs. The characteristic of in vitro models (n = 16) for Mycobacterium tuberculosis dormant state and in vivo models (n = 14) for the latent tuberculosis infection involving several animal species published to date are presented in this review. A brief description of the models and the results obtained by the authors are presented. The analysis of the published data reflects the list of methodological procedures that allow researchers to study the mechanism of the transition of M. tuberculosis cells to a dormant state and reverse to metabolically active state, as well as the process of conversion of active tuberculosis infection to a latent tuberculosis and reactivation.

Abstracts

2008 ◽  
Vol 27 (6) ◽  
pp. 405-405
Author(s):  
David J. Dix
Keyword(s):  
Risk Assessment ◽  
High Throughput ◽  
Environmental Protection Agency ◽  
High Throughput Screening ◽  
Human Health Risk ◽  
Environmental Chemicals ◽  
In Vitro Assays ◽  
The Impact ◽  
Toxicity Pathways

The U.S. Environmental Protection Agency (EPA), National Toxicology Program (NTP), and National Institutes of Health (NIH) Chemical Genomics Center (NCGC) have complementary research programs designed to improve chemical toxicity evaluations by developing high throughput screening (HTS) methods that evaluate the impact of environmental chemicals on key toxicity pathways. These federal partners are coordinating an extension of the EPA’s ToxCast program, the NTP’s HTS initiative, and the NCGC’s Molecular Libraries Initiative into a collaborative research program focused on identifying toxicity pathways and developing in vitro assays to characterize the ability of chemicals to perturb those pathways. The goal is to develop new paradigm for high throughput toxicity testing that collects mechanistic and quantitative data from in vitro assays measuring chemical modulation of biological processes involved in the progression to toxicity. As toxicity pathways are identified, the in vitro assays can be optimized for comparison to in vivo animal studies, and for predicting effects in humans. Subsequent computational modeling of toxicity pathway responses and appropriate chemical dosimetry will need to be developed to make these predictions relevant for human health risk assessment. This work was reviewed by EPA and approved for publication but does not necessarily reflect official Agency policy. Index Terms: Toxicogenomics, High Throughput Screening/Testing, EPA ToxCast, Chemical Risk Assessment

scholarly journals Intestinal fermentation in vitro models to study food-induced gut microbiota shift: an updated review

2020 ◽  
Vol 367 (12) ◽  
Author(s):  
Lorenzo Nissen ◽  
Flavia Casciano ◽  
Andrea Gianotti
Keyword(s):  
Gut Microbiota ◽  
In Vitro Models ◽  
Experimental Conditions ◽  
Applied Microbiology ◽  
Microbial Groups ◽  
Technical Features ◽  
State Of The Science ◽  
The Impact ◽  
Small Working

ABSTRACT In vitro gut fermentation models were firstly introduced in nutrition and applied microbiology research back in the 1990s. These models have improved greatly during time, mainly over the resemblance to the complexity of digestion stages, the replication of experimental conditions, the multitude of ecological parameters to assay. The state of the science is that the most competitive models shall include a complex gut microbiota, small working volumes, distinct interconnected compartments and rigorous bio-chemical and ecological settings, controlled by a computer, as well as a free-hands accessibility, not to contaminate the mock microbiota. These models are a useful tool to study the impact of a given diet compound, e.g. prebiotics, on the human gut microbiota. The principal application is to focus on the shift of the core microbial groups and selected species together with their metabolites, assaying their diversity, richness and abundance in the community over time. Besides, it is possible to study how a compound is digested, which metabolic pathways are triggered, and the type and quantity of microbial metabolites produced. Further prospective should focus on challenges with pathogens as well as on ecology of gut syndromes. In this minireview an updated presentation of the most used intestinal models is presented, basing on their concept, technical features, as well as on research applications.

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