Cardiovascular physiology teaching: computer simulations vs. animal demonstrations.

1994 ◽  
Vol 266 (6) ◽  
pp. S36 ◽  
Author(s):  
R W Samsel ◽  
G A Schmidt ◽  
J B Hall ◽  
L D Wood ◽  
S G Shroff ◽  
...  
Keyword(s):  
Conceptual Knowledge ◽  
Animal Studies ◽  
Computer Software ◽  
Cost Effective ◽  
Multiple Organ ◽  
Cardiovascular Physiology ◽  
Laboratory Observation ◽  
Organ Systems ◽  
Laboratory Tool

The roots of physiology lie in laboratory observation, and physiology courses continue to rely on laboratory observation to provide students with practical information to correlate with their developing base of conceptual knowledge. To this end, animal laboratories provide a functioning example of interactions among organ systems and a source of data for student analysis. However, there are continuing objections to using animals for teaching, and animal labs are costly in time and effort. As an alternative laboratory tool, computer software can simulate the operation of multiple organ systems: responses to interventions illustrate intrinsic organ behavior and integrated systems physiology. Advantages of software over animal studies include alteration of variables that are not easily changed in vivo, repeated interventions, and cost-effective hands-on student access. Nevertheless, simulations miss intangible aspects of experimental physiology, and results depend critically on the assumptions of the model. We used both computer and animal demonstrations in teaching cardiovascular physiology to first-year medical students. The students rated both highly, but the computer-based session received a higher rating. We believe that both forms of teaching have educational merit. At the introductory level, the computer appears to provide an effective alternative.

scholarly journals Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

2018 ◽  
Vol 19 (12) ◽  
pp. 4121 ◽  
Author(s):  
Amaal Abdulle ◽  
Harry van Goor ◽  
Douwe Mulder
Keyword(s):  
Hydrogen Sulfide ◽  
Systemic Sclerosis ◽  
Animal Studies ◽  
Therapeutic Option ◽  
Multiple Organ ◽  
Current Data ◽  
Organ Systems ◽  
Transsulfuration Pathway ◽  
Exact Etiology ◽  
Vascular Physiology

Systemic sclerosis (SSc) is a lethal disease that is characterized by auto-immunity, vascular injury, and progressive fibrosis of multiple organ systems. Despite the fact that the exact etiology of SSc remains unknown, oxidative stress has been associated with a large range of SSc-related complications. In addition to the well-known detrimental properties of reactive oxygen species (ROS), gasotransmitters (e.g., nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)) are also thought to play an important role in SSc. Accordingly, the diverse physiologic actions of NO and CO and their role in SSc have been previously studied. Recently, multiple studies have also shown the importance of the third gasotransmitter H2S in both vascular physiology and pathophysiology. Interestingly, homocysteine (which is converted into H2S through the transsulfuration pathway) is often found to be elevated in SSc patients; suggesting defects in the transsulfuration pathway. Hydrogen sulfide, which is known to have several effects, including a strong antioxidant and vasodilator effect, could potentially play a prominent role in the initiation and progression of vasculopathy. A better understanding of the actions of gasotransmitters, like H2S, in the development of SSc-related vasculopathy, could help to create early interventions to attenuate the disease course. This paper will review the role of H2S in vascular (patho-)physiology and potential disturbances in SSc. Moreover, current data from experimental animal studies will be reviewed. Lastly, we will evaluate potential interventional strategies.

scholarly journals Neuroinvasion of SARS-CoV-2 in human and mouse brain

2021 ◽  
Vol 218 (3) ◽  
Author(s):  
Eric Song ◽  
Ce Zhang ◽  
Benjamin Israelow ◽  
Alice Lu-Culligan ◽  
Alba Vieites Prado ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Immune Cell ◽  
Multiple Organ ◽  
Type I ◽  
Organ Systems ◽  
The Central Nervous System ◽  
Interferon Responses ◽  
The Brain ◽  
Immune Cell Infiltrates

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

scholarly journals Pleiotropic Phenotype of a Genomic Knock-In of an RGS-Insensitive G184S Gnai2 Allele

2006 ◽  
Vol 26 (18) ◽  
pp. 6870-6879 ◽  
Author(s):  
Xinyan Huang ◽  
Ying Fu ◽  
Raelene A. Charbeneau ◽  
Thomas L. Saunders ◽  
Douglas K. Taylor ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Cell Function ◽  
Immune Cell ◽  
Multiple Organ ◽  
Rgs Proteins ◽  
Total Contribution ◽  
Pleiotropic Phenotype ◽  
Organ Systems

ABSTRACT Signal transduction via guanine nucleotide binding proteins (G proteins) is involved in cardiovascular, neural, endocrine, and immune cell function. Regulators of G protein signaling (RGS proteins) speed the turn-off of G protein signals and inhibit signal transduction, but the in vivo roles of RGS proteins remain poorly defined. To overcome the redundancy of RGS functions and reveal the total contribution of RGS regulation at the Gαi2 subunit, we prepared a genomic knock-in of the RGS-insensitive G184S Gnai2 allele. The Gαi2 G184S knock-in mice show a dramatic and complex phenotype affecting multiple organ systems (heart, myeloid, skeletal, and central nervous system). Both homozygotes and heterozygotes demonstrate reduced viability and decreased body weight. Other phenotypes include shortened long bones, a markedly enlarged spleen, elevated neutrophil counts, an enlarged heart, and behavioral hyperactivity. Heterozygous Gαi2 +/G184S mice show some but not all of these abnormalities. Thus, loss of RGS actions at Gαi2 produces a dramatic and pleiotropic phenotype which is more evident than the phenotype seen for individual RGS protein knockouts.

scholarly journals mito-QC illuminates mitophagy and mitochondrial architecture in vivo

2016 ◽  
Vol 214 (3) ◽  
pp. 333-345 ◽  
Author(s):  
Thomas G. McWilliams ◽  
Alan R. Prescott ◽  
George F.G. Allen ◽  
Jevgenia Tamjar ◽  
Michael J. Munson ◽  
...  
Keyword(s):  
Quality Control ◽  
Cell Biology ◽  
Multiple Organ ◽  
Mitochondrial Morphology ◽  
In Vivo Detection ◽  
Developing Heart ◽  
Adult Kidney ◽  
Organ Systems ◽  
Essential Quality

Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed “mito-QC,” a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities.

scholarly journals Zinc Finger Protein Zbtb20 Is Essential for Postnatal Survival and Glucose Homeostasis

2009 ◽  
Vol 29 (10) ◽  
pp. 2804-2815 ◽  
Author(s):  
Andrew P. R. Sutherland ◽  
Hai Zhang ◽  
Ye Zhang ◽  
Monia Michaud ◽  
Zhifang Xie ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Glucose Homeostasis ◽  
Knockout Mice ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Postnatal Growth ◽  
Multiple Organ ◽  
Wild Type Littermate ◽  
Organ Systems

ABSTRACT Zbtb20 is a member of the POK family of proteins, which function primarily as transcriptional repressors via interactions mediated by their conserved C2H2 Krüppel type zinc finger and BTB/POZ domains. To define the function of Zbtb20 in vivo, we generated knockout mice by homologous recombination. Zbtb20 null mice display a stark phenotype characterized by postnatal growth retardation, metabolic dysfunction, and lethality. Zbtb20 knockout mice displayed abnormal glucose homeostasis, hormonal responses, and depletion of energy stores, consistent with an energetic deficit. Additionally, increased serum bilirubin and alanine aminotransferase levels were suggestive of liver dysfunction. To identify potential liver-specific Zbtb20 target genes, we performed transcript profiling studies on liver tissue from Zbtb20 knockout mice and wild-type littermate controls. These studies identified sets of genes involved in growth, metabolism, and detoxification that were differentially regulated in Zbtb20 knockout liver. Transgenic mice expressing Zbtb20 in the liver were generated and crossed onto the Zbtb20 knockout background, which resulted in no significant normalization of growth or glucose metabolism but a significant increase in life span compared to controls. These data indicate that the phenotype of Zbtb20 knockout mice results from liver-dependent and -independent defects, suggesting that Zbtb20 plays nonredundant roles in multiple organ systems.

scholarly journals Lysophospholipid (S1P) receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Victoria Blaho ◽  
Jerold Chun ◽  
Deepa Jonnalagadda ◽  
Yasuyuki Kihara ◽  
Hirotaka Mizuno ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Radioligand Binding ◽  
Cell Types ◽  
Receptor Activation ◽  
Multiple Organ ◽  
S1p Receptors ◽  
Organ Systems ◽  
Sphingosine 1 Phosphate ◽  
Heterologous Expression Systems

Sphingosine 1-phosphate (S1P) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid receptors [70]) are activated by the endogenous lipid sphingosine 1-phosphate (S1P). Originally cloned as orphan members of the endothelial differentiation gene (edg) family, current gene names have been designated as S1P1R through S1P5R [52]. S1PRs, particularly S1P1, are expressed throughout all mammalian organ systems. Ligand delivery occurs via two known carriers (or "chaperones"): albumin and HDL-bound apolipoprotein M (ApoM), the latter of which elicits biased agonist signaling by S1P1 in multiple cell types [15, 39]. The five S1PRs, two chaperones, and active cellular metabolism have complicated analyses of receptor ligand binding in native systems. Signaling pathways and physiological roles have been characterized through radioligand binding in heterologous expression systems, targeted deletion of the different S1PRs, and most recently, mouse models that report in vivo S1P1R activation [74, 76]. A crystal structure of an S1P1-T4 fusion protein confirmed aspects of ligand binding, specificity, and receptor activation determined previously through biochemical and genetic studies [48, 14]. fingolimod (FTY720), the first drug to target any of the lysophospholipid receptors, binds to four of the five S1PRs, and was the first oral therapy for multiple sclerosis [26]. The mechanisms of action of fingolimod and other S1PR modulating drugs in development include binding S1PRs in multiple organ systems, e.g., immune and nervous systems, although the precise nature of their receptor interactions requires clarification [107, 28, 43, 44].

scholarly journals Searching for Clinically Relevant Biomarkers in Geriatric Oncology

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Theodora Katsila ◽  
George P. Patrinos ◽  
Dimitrios Kardamakis
Keyword(s):  
Decision Making ◽  
Ethical Issues ◽  
Unmet Need ◽  
Geriatric Oncology ◽  
Cost Effective ◽  
Multiple Organ ◽  
Health Concern ◽  
Policy Makers ◽  
Mortality And Morbidity ◽  
Organ Systems

Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

scholarly journals HIF1α is a direct regulator of steroidogenesis in the adrenal gland

2021 ◽  
Author(s):  
Deepika Watts ◽  
Johanna Stein ◽  
Ana Meneses ◽  
Nicole Bechmann ◽  
Ales Neuwirth ◽  
...  
Keyword(s):  
Multiple Organ ◽  
Hypoxia Inducible Factors ◽  
Adrenocortical Cells ◽  
Steroid Production ◽  
Hormone Synthesis ◽  
Organ Systems ◽  
Direct Regulator ◽  
Endogenous Steroid ◽  
Endogenous Steroid Hormones

AbstractEndogenous steroid hormones, especially glucocorticoids and mineralocorticoids, derive from the adrenal cortex, and drastic or sustained changes in their circulatory levels affect multiple organ systems. Although hypoxia signaling in steroidogenesis has been suggested, knowledge on the true impact of the HIFs (Hypoxia-Inducible Factors) in the adrenocortical cells of vertebrates is scant. By creating a unique set of transgenic mouse lines, we reveal a prominent role for HIF1α in the synthesis of virtually all steroids in vivo. Specifically, mice deficient in HIF1α in adrenocortical cells displayed enhanced levels of enzymes responsible for steroidogenesis and a cognate increase in circulatory steroid levels. These changes resulted in cytokine alterations and changes in the profile of circulatory mature hematopoietic cells. Conversely, HIF1α overexpression resulted in the opposite phenotype of insufficient steroid production due to impaired transcription of necessary enzymes. Based on these results, we propose HIF1α to be a vital regulator of steroidogenesis as its modulation in adrenocortical cells dramatically impacts hormone synthesis with systemic consequences. In addition, these mice can have potential clinical significances as they may serve as essential tools to understand the pathophysiology of hormone modulations in a number of diseases associated with metabolic syndrome, auto-immunity or even cancer.

Antidiabetic properties of dietary chrysin: a cellular mechanism review

2021 ◽  
Vol 21 ◽  
Author(s):  
Rita Marleta Dewi ◽  
Megawati Megawati ◽  
Lucia Dwi Antika
Keyword(s):  
Animal Studies ◽  
Multiple Organ ◽  
Antidiabetic Activity ◽  
Antidiabetic Agent ◽  
In Vivo Experiments ◽  
Chronic Hyperglycemia ◽  
Organ Failures

: Diabetes mellitus is the most common chronic metabolic disorder and is considered one of the leading causes of morbidity and mortality. The improperly-treated chronic hyperglycemia of diabetes has been related to several long-term complications and multiple organ failures, including nephropathy, which can lead to kidney failure, retinopathy with the potential loss of vision, and cardiovascular symptoms. Current commercially available synthetic glucose-lowering agents have been reported to have several adverse effects. Therefore, the search for alternative remedies such as medicinal plants and their active compounds have attracted attention. Chrysin is an active flavonoid that exists widely in various plants and diets and has been reported to possess pharmacological properties, including antidiabetic activity. Many studies have been conducted to characterize the antidiabetic of chrysin, as well as its potential pathways, in in vitro and in vivo experiments. Chrysin has shown promise as an antidiabetic agent in animal studies, thus, demonstrating its potential to be developed as an antidiabetic drug. This review discussed the antidiabetic action of chrysin and its mechanisms, including targeting different mechanisms such as stimulation of insulin signaling, blockage of endoplasmic reticulum stress and oxidative damage, promotion of skeletal glucose uptake, as well as modulation of apoptosis and autophagy signaling. Additionally, this review would be useful for further studies regarding the mechanism of work of plant derived-compound as a potential antidiabetic agent.

scholarly journals Neuroinvasion of SARS-CoV-2 in human and mouse brain

2020 ◽  
Author(s):  
Eric Song ◽  
Ce Zhang ◽  
Benjamin Israelow ◽  
Alice Lu-Culligan ◽  
Alba Vieites Prado ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Immune Cell ◽  
Multiple Organ ◽  
Cns Infection ◽  
Type I ◽  
Organ Systems ◽  
Pathologic Features ◽  
The Central Nervous System ◽  
The Brain

SummaryAlthough COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

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