scholarly journals EXPERIMENTAL MODELS OF FETOPLACEENTAL INSUFFICIENCY IN ANIMALS (LITERATURE REVIEW AND OWN OBSERVATIONS)

Author(s):  
N. Yu. Seliukova ◽  
K. V. Misyura ◽  
G. V. Storozhenko

This literature review is devoted to experimental models of placental disorders in animals. Today, our knowledge of the structure and function of the placenta during pregnancy is remaining limited. The use of new technologies and imaging methods in animals that can provide safe monitoring of the growth and function of the placenta in vivo requires preclinical studies and trials in appropriately developed animal models that can be easily translated into a clinical setting. All this, of course, requires the use of test animals for modelling placental pathologies. The review considers the positive and negative aspects of various animals and methods of modelling the pathological conditions during pregnancy. In the experiment, models of fetoplacental insufficiency are very often used, arising from oxidative stress and activation of free radical oxidation. To simulate the experimental fetoplacental insufficiency caused by histotoxic hypoxia, the xenobiotic tetrachloromethane is used. Women of very young and mature reproductive age have a high risk of fetoplacental insufficiency. It is not known exactly how placental insufficiency in mothers will affect the sexual development of pubertal offspring. That is why we conducted a comprehensive experimental study on this issue at the base of V. Danilevsky Institute of Endocrine Pathology Problems, NAMS of Ukraine. To solve this problem, our institute has developed and proposed a new pharmaceutical composition that should not only contribute to the correction of placental insufficiency, but also has a certain prophylactic value for maintaining reproductive potential in adulthood. The study was carried out on Wistar rats of two age groups. We modelled experimental fetoplacental insufficiency and then corrected it with this pharmaceutical composition. Our study made it possible to establish that fetoplacental insufficiency has a different effect on the formation of the reproductive system in male and female rats in puberty. Prophylactic adding of the composition to the food for pregnant female rats with modelled placental insufficiency leads to the decrease in reproductive diseases of their offspring in puberty. Research on animal models provides important insight into the molecular and functional mechanisms underlying fetoplacental insufficiency and intrauterine growth retardation, as it enables to carry out studies, which are not possible in pregnant women.

2020 ◽  
Vol 5 (6) ◽  
pp. 362-369
Author(s):  
N. Yu. Seliukova ◽  
◽  

The literature review presents the results of processing literature data on one of the topical issues of obstetrics and reproductive medicine - placental insufficiency. According to the World Health Organization, the number of infertile couples is gradually increasing in the world every year. In Ukraine, the frequency of infertile marriages among persons of reproductive age ranges from 12 to 18%. The state of the reproductive system of an adult female is influenced by many factors, from embryonic development to the lifestyle of an adult woman. With an inadequate effect of harmful factors on the fetus, the fetoplacental complex may not react properly, and this is how the symptom complex of disorders arises both on the part of the mother and on the part of the fetus, which is called placental insufficiency, it negatively affects the condition and quality of pregnancy and childbirth. Numerous studies have proven the existence of a connection between the effect of certain factors during pregnancy on the state and functionality of various body systems already in adulthood. It was shown that children who were born from mothers with placental insufficiency suffering from cardiovascular diseases have fewer elastic fibers in the arteries, nephrons in the kidneys. In addition, the pancreas has fewer insulin-producing β-cells and reduced vascularization, as well as altered structure and maturation of the brain, lungs (respiratory distress syndrome) and liver, joint dysplasia, and an imbalance of the immune system. When studying the long-term effects of placental insufficiency, various disorders of physical and mental development are observed, as well as increased somatic and infectious morbidity of newborns and children in the first year of life, in the future it may be the cause of the development of diseases such as arterial hypertension, diabetes mellitus, metabolic syndrome, etc. Conclusion. Our studies have shown the negative impact of placental insufficiency on the reproductive system of adult offspring of rats of two sexes who were born to mothers of two age groups. In particular, the level of testosterone in female offspring was increased against the background of the altered structure of the estrous cycle and the pathological state of ovarian histology. In the male offspring, on the contrary, the total testosterone level decreased, but the histology of the testes and the functional state of the sperm remained unchanged


2014 ◽  
Vol 2014 ◽  
pp. 1-21 ◽  
Author(s):  
Andrea Mess

Here a survey of placental evolution is conducted. Placentation is a key factor for the evolution of placental mammals that had evolved an astonishing diversity. As a temporary organ that does not allow easy access, it is still not well understood. The lack of data also is a restriction for better understanding of placental development, structure, and function in the human. Animal models are essential, because experimental access to the human placenta is naturally restricted. However, there is not a single ideal model that is entirely similar to humans. It is particularly important to establish other models than the mouse, which is characterised by a short gestation period and poorly developed neonates that may provide insights only for early human pregnancy. In conclusion, current evolutionary studies have contributed essentially to providing a pool of experimental models for recent and future approaches that may also meet the requirements of a long gestation period and advanced developmental status of the newborn in the human. Suitability and limitations of taxa as alternative animal models are discussed. However, further investigations especially in wildlife taxa should be conducted in order to learn more about the full evolutionary plasticity of the placenta system.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 824
Author(s):  
Andrea Capucciati ◽  
Fabio A. Zucca ◽  
Enrico Monzani ◽  
Luigi Zecca ◽  
Luigi Casella ◽  
...  

Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1337.2-1337
Author(s):  
T. W. Swinnen ◽  
M. Willems ◽  
I. Jonkers ◽  
F. P. Luyten ◽  
J. Vanrenterghem ◽  
...  

Background:The personal and societal burden of knee osteoarthritis (KOA) urges the research community to identify factors that predict its onset and progression. A mechanistic understanding of disease is currently lacking but needed to develop targeted interventions. Traditionally, risk factors for KOA are termed ‘local’ to the joint or ‘systemic’ referring to whole-body systems. There are however clear indications in the scientific literature that contextual factors such as socioeconomic position merit further scientific scrutiny, in order to justify a more biopsychosocial view on risk factors in KOA.Objectives:The aims of this systematic literature review were to assess the inclusion of socioeconomic factors in KOA research and to identify the impact of socioeconomic factors on pain and function in KOA.Methods:Major bibliographic databases, namely Medline, Embase, CINAHL, Web of Science and Cochrane, were independently screened by two reviewers (plus one to resolve conflicts) to identify research articles dealing with socioeconomic factors in the KOA population without arthroplasty. Included studies had to quantify the relationship between socioeconomic factors and pain or function. Main exclusion criteria were: a qualitative design, subject age below 16 years and articles not written in English or Dutch. Methodological quality was assessed via the Cochrane risk of bias tools for randomized (ROB-II) and non-randomized intervention studies (ROBIN-I) and the Newcastle-Ottawa Scale for assessing the quality of non-randomised studies. Due to heterogeneity of studies with respect to outcomes assessed and analyses performed, no meta-analysis was performed.Results:Following de-duplication, 7639 articles were available for screening (120 conflicts resolved without a third reader). In 4112 articles, the KOA population was confirmed. 1906 (25%) were excluded because of knee arthroplasty and 1621 (21%) because of other issues related to the population definition. Socioeconomic factors could not be identified in 4058 (53%) papers and were adjusted for in 211 (3%) articles. In the remaining papers covering pain (n=110) and/or function (n=81), education (62%) and race (37%) were most frequently assessed as socioeconomic factors. A huge variety of mainly dichotomous or ordinal socioeconomic outcomes was found without further methodological justification nor sensitivity analysis to unravel the impact of selected categories. Although the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most popular instrument to assess pain and function, data pooling was not possible as socioeconomic factors estimates were part of multilevel models in most studies. Overall results showed that lower education and African American race were consistent predictors of pain and poor function, but those effects diminished or disappeared when psychological aspects (e.g. discrimination) or poverty estimates were taken into account. When function was assessed using self-reported outcomes, the impact of socioeconomic factors was more clear versus performance-based instruments. Quality of research was low to moderate and the moderating or mediating impact of socioeconomic factors on intervention effects in KOA is understudied.Conclusion:Research on contextual socioeconomic factors in KOA is insufficiently addressed and their assessment is highly variable methodologically. Following this systematic literature review, we can highlight the importance of implementing a standardised and feasible set of socioeconomic outcomes in KOA trials1, as well as the importance of public availability of research databases including these factors. Future research should prioritise the underlying mechanisms in the effect of especially education and race on pain and function and assess its impact on intervention effects to fuel novel (non-)pharmacological approaches in KOA.References:[1]Smith TO et al. The OMERACT-OARSI Core Domain Set for Measurement in Clinical Trials of Hip and/or Knee Osteoarthritis J Rheumatol 2019. 46:981–9.Disclosure of Interests:None declared.


Author(s):  
Peter H. Rudebeck ◽  
Alicia Izquierdo

AbstractEfficient foraging is essential to survival and depends on frontal cortex in mammals. Because of its role in psychiatric disorders, frontal cortex and its contributions to reward procurement have been studied extensively in both rodents and non-human primates. How frontal cortex of these animal models compares is a source of intense debate. Here we argue that translating findings from rodents to non-human primates requires an appreciation of both the niche in which each animal forages as well as the similarities in frontal cortex anatomy and function. Consequently, we highlight similarities and differences in behavior and anatomy, before focusing on points of convergence in how parts of frontal cortex contribute to distinct aspects of foraging in rats and macaques, more specifically. In doing so, our aim is to emphasize where translation of frontal cortex function between species is clearer, where there is divergence, and where future work should focus. We finish by highlighting aspects of foraging for which have received less attention but we believe are critical to uncovering how frontal cortex promotes survival in each species.


RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001549 ◽  
Author(s):  
Aurélie Najm ◽  
Alessia Alunno ◽  
Xavier Mariette ◽  
Benjamin Terrier ◽  
Gabriele De Marco ◽  
...  

BackgroundThe SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19.MethodsTwo reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration.ResultsOf the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality.ConclusionsSARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies.


2012 ◽  
Vol 302 (3) ◽  
pp. R321-R330 ◽  
Author(s):  
Ahmed A. Elmarakby

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yunlong Zhang ◽  
Feng Tan ◽  
Pingyi Xu ◽  
Shaogang Qu

Parkinson’s disease (PD) is the most common movement disorder disease in the elderly and is characterized by degeneration of dopamine neurons and formation of Lewy bodies. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). If glutamate is not removed promptly in the synaptic cleft, it will excessively stimulate the glutamate receptors and induce excitotoxic effects on the CNS. With lack of extracellular enzyme to decompose glutamate, glutamate uptake in the synaptic cleft is mainly achieved by the excitatory amino acid transporters (EAATs, also known as high-affinity glutamate transporters). Current studies have confirmed that decreased expression and function of EAATs appear in PD animal models. Moreover, single unilateral administration of EAATs inhibitor in the substantia nigra mimics several PD features and this is a solid evidence supporting that decreased EAATs contribute to the process of PD. Drugs or treatments promoting the expression and function of EAATs are shown to attenuate dopamine neurons death in the substantia nigra and striatum, ameliorate the behavior disorder, and improve cognitive abilities in PD animal models. EAATs are potential effective drug targets in treatment of PD and thus study of relationship between EAATs and PD has predominant medical significance currently.


2015 ◽  
Vol 9s1 ◽  
pp. JEN.S32735
Author(s):  
Darryl J. Mayeaux ◽  
Sarah M. Tandle ◽  
Sean M. Cilano ◽  
Matthew J. Fitzharris

In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action.


2021 ◽  
Vol 8 (2) ◽  
pp. 141-160
Author(s):  
Ekaterina Glebova ◽  
Michel Desbordes

The massive uptake of digital technologies has changed the way how fans and the sports service field communicate and interact. In the current paper, we would like to emphasize the role of technology holistically in sport spectators customer experiences (SSCX) as a "game-changer" marketing in sports and the digitalization of SSCX. In this paper, we aim to explore and qualitatively describe by interviewees verbatim how new technologies impact SSCX. It draws on the literature review, combined with the primary data collected on unstructured interviews with international sport management and technology experts (N=10). It brings sports marketing insights followed by examples from industry professionals. Iterative analysis of data combined with literature review let us achieve to outline the crucial points and trends of technological transformations in sports spectacle. We offer an updated perspective on the SSCX through the prism of the impact of digital technologies and reshaping sports consumption culture. To this end, we develop a conceptual model that captures the nature of modern SSCX influenced by digital technologies. Keywords: technological transformation, sports spectacle, customer experience, co-creation, connectivity


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