scholarly journals The path toward ectogenesis: looking beyond the technical challenges

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Seppe Segers
Keyword(s):  
Neonatal Intensive Care ◽  
Animal Studies ◽  
Current Data ◽  
Safety Testing ◽  
Future Challenges ◽  
Critical Issues ◽  
Expected Benefits ◽  
Physical Impact ◽  
Biological Parenthood ◽  
Experimental Use

Abstract Background Breakthroughs in animal studies make the topic of human application of ectogenesis for medical and non-medical purposes more relevant than ever before. While current data do not yet demonstrate a reasonable expectation of clinical benefit soon, several groups are investigating the feasibility of artificial uteri for extracorporeal human gestation. Main text This paper offers the first comprehensive and up to date discussion of the most important pros and cons of human ectogenesis in light of clinical application, along with an examination of crucial ethical (and legal) issues that continued research into, and the clinical translation of, ectogenesis gives rise to. The expected benefits include advancing prenatal medicine, improving neonatal intensive care, and providing a novel pathway towards biological parenthood. This comes with important future challenges. Prior to human application, important questions have to be considered concerning translational research, experimental use of human fetuses and appropriate safety testing. Key questions are identified regarding risks to ectogenesis’ subjects, and the physical impact on the pregnant person when transfer from the uterus to the artificial womb is required. Critical issues concerning proportionality have to be considered, also in terms of equity of access, relative to the envisaged application of ectogenesis. The advent of ectogenesis also comes with crucial issues surrounding abortion, extended fetal viability and moral status of the fetus. Conclusions The development of human ectogenesis will have numerous implications for clinical practice. Prior to human testing, close consideration should be given to whether (and how) ectogenesis can be introduced as a continuation of existing neonatal care, with due attention to both safety risks to the fetus and pressures on pregnant persons to undergo experimental and/or invasive procedures. Equally important is the societal debate about the acceptable applications of ectogenesis and how access to these usages should be prioritized. It should be anticipated that clinical availability of ectogenesis, possibly first as a way to save extremely premature fetuses, may spark demand for non-medical purposes, like avoiding physical and social burdens of pregnancy.

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 The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1679 ◽  
Author(s):  
David Khalaf ◽  
Marcus Krüger ◽  
Markus Wehland ◽  
Manfred Infanger ◽  
Daniela Grimm
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Animal Studies ◽  
Current Data ◽  
No Production ◽  
First Pass Metabolism ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Antihypertensive Properties ◽  
Pass Metabolism

Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate inaccessibility. This review aimed to investigate whether oral administration of the amino acids l-arginine (Arg) and l-citrulline (Cit), which are potential substrates for eNOS, could effectively reduce BP by increasing NO production. Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg. The exact mechanism by which Cit and Arg exert their effect is not fully understood, as normal plasma Arg concentration greatly exceeds the Michaelis constant (Km) of eNOS. Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the “l-arginine paradox”.

Thrombolytic Salvage of the Frostbitten Upper Extremity: A Systematic Review

Hand ◽  
2020 ◽  
pp. 155894472094006
Author(s):  
James Drinane ◽  
Adee J. Heiman ◽  
Joseph A. Ricci ◽  
Ashit Patel
Keyword(s):  
Systematic Review ◽  
Thrombolytic Therapy ◽  
Upper Extremity ◽  
Animal Studies ◽  
English Language ◽  
Case Series ◽  
Current Data ◽  
Ischemic Tissue ◽  
Promising Treatment ◽  
Salvage Rate

Background Vascular thrombosis secondary to frostbite can lead to ischemic tissue damage in severe cases. Threatened extremities may be salvaged with thrombolytics to restore perfusion; however, current data are limited to single institution case series. The authors performed a systematic review to determine the efficacy of thrombolytic therapy in treating upper extremity frostbite. Methods PubMed, EBSCO, and Google Scholar were queried using the keywords “thrombolytics,” “frostbite,” “fibrinolytics,” and “tPA.” Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as intraarterial (IA) or intravenous (IV) administration of tissue plasminogen activator (tPA), alteplase, urokinase, streptokinase, or any tPA derivative. Results A total of 42 studies were identified, with 13 satisfying inclusion criteria. Eight studies reported catheter-directed IA thrombolysis, four reported systemic IV administration, and 1 reported both methods. A total of 157 patients received thrombolytics. In all, 73 upper extremity digits were treated by IA route and 136 digits were treated by IV route. Overall upper extremity digit salvage rate was 59%. There was a significantly higher salvage rate in digits treated by the IA route compared to the IV route. Conclusions Thrombolytics, particularly when administered by the intra-arterial route, are emerging as a promising treatment of severe frostbite of the upper extremity, increasing digit salvage rates.

scholarly journals Iterative Cellular Screening System for Nanoparticle Safety Testing

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Franziska Sambale ◽  
Frank Stahl ◽  
Ferdinand Rüdinger ◽  
Dror Seliktar ◽  
Cornelia Kasper ◽  
...  
Keyword(s):  
Animal Studies ◽  
Titanium Dioxide Nanoparticles ◽  
Three Dimensional ◽  
Good Method ◽  
Screening System ◽  
Human Beings ◽  
Safety Testing ◽  
Mammalian Cell Lines ◽  
Set Up

Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimicin vivoconditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

A Prototype Infant Incubator for Heliox Therapy

2006 ◽  
Vol 40 (2) ◽  
pp. 150-163 ◽  
Author(s):  
Clifford J. Singhaus ◽  
Suzanne M. Touch ◽  
Jay S. Greenspan ◽  
Marla R. Wolfson ◽  
Thomas H. Shaffer
Keyword(s):  
Neonatal Intensive Care ◽  
Animal Studies ◽  
Performance Criteria ◽  
In Vitro Tests ◽  
Original Design ◽  
Experimental Conditions ◽  
Infant Incubator ◽  
Opening And Closing

Abstract Heliox (Hx) gas has been shown to improve pulmonary function in infants, but methods for its delivery are invasive and problematic. To this end, we modified an Isolette (Hill-Rom Air-Shields) infant incubator (Hxl) to deliver Hx respiratory gas mixtures noninvasively while providing thermal stability for neonatal care in the Neonatal Intensive Care Unit (NICU). In vitro tests and in vivo animal studies were performed to compare the original design specifications and established baseline performance criteria for the Hxl design. The experimental environments at 50% and 80% relative humidity (RH) consisted of helium (He) with 21% and 50% O2 and control (C) of 21% and 50% O2 with the balance nitrogen (N2). Elapsed times to steady state (SS) and recovery time back to SS (OCDss) due to opening and closing the door were recorded for each variable. All rabbits survived and appeared comfortable during all experimental conditions. These data show that the newly designed Isolette provides similar thermal, O2, CO2, and RH responses as the control incubator. Based on these positive safety/efficacy studies, study of the therapeutic impact of Hxl care on neonatal growth and development is in progress.

Final Report on the Safety Assessment of HC Blue No. 1

1994 ◽  
Vol 13 (5) ◽  
pp. 344-360
Keyword(s):  
Animal Studies ◽  
Current Data ◽  
Female Rats ◽  
Male Rats ◽  
Final Report ◽  
Positive Trend ◽  
Hair Dyes ◽  
Pregnant Rats ◽  
Hepatocellular Carcinomas ◽  
Dose Dependent

The aromatic amine HC Blue No. 1 is a hair colorant intended exclusively for use in hair dyes. While this colorant had previously been used in concentrations up to 1.6%, current information indicates it is not presently used in any hair dyes. Animal studies indicate this ingredient is absorbed slowly through the skin. Short-term and subchronic animal toxicity studies show a dose-dependent reduction in weight gain. HC Blue No. 1 was mutagenic in some, but not all, test systems, and was associated with fetal bone malformations when given orally to pregnant rats at levels that were maternally toxic. In a National Toxicology Program feeding study, dosed male rats had a positive trend in incidence of hepatic neoplastic nodules, but not in hepatic carcinomas; dosed female rats showed a positive trend in the incidence of alveolar/bronchiolar neoplasms; and mice of both sexes showed an increase in hepatocellular carcinomas. Although it is recognized that further dermal carcinogenicity data would help clarify the different findings in the current data, such information is not expected, and it is concluded on the basis of the data that are available in this report that HC Blue No. 1 is unsafe for use in cosmetic formulations (hair dyes).

A semiotic analysis on cultural meanings of eating horsemeat

2018 ◽  
Vol 21 (3) ◽  
pp. 337-352 ◽  
Author(s):  
Hanna Leipämaa-Leskinen ◽  
Henna Syrjälä ◽  
Minna-Maarit Jaskari
Keyword(s):  
Food Consumption ◽  
Cultural Context ◽  
Animal Studies ◽  
Special Kind ◽  
Online News ◽  
Current Data ◽  
Discussion Forums ◽  
Semiotic Analysis ◽  
Semantic Meaning ◽  
Content Type

Purpose Drawing on food consumption research and human-animal studies, this paper aims to explore how the meanings related to a living horse may be transferred to those of horsemeat. This is accomplished by constructing a nuanced understanding of how different semantic meaning categories of accepting/avoiding consuming horsemeat relate to each other. Design/methodology/approach The current data are collected from various sources of media discussions, including online news, online discussion forums, blog postings and printed articles, generated in Finland after the year 2013. The data are analysed applying Greimas’ (1987) semiotic square to open up the semantic meaning categories appearing in the media discussions. Findings The semiotic square shows that the meanings of horsemeat arise between the binary oppositions of human-like and animal-like. In this structure, the category of human-like makes eating horsemeat impossible, whereas the category of animal-like makes horsemeat good to eat. The main categories are completed and contrasted by the categories of not human-like and not animal-like. They represent horsemeat as an acceptable food, but only after certain justifications. Research limitations/implications The data are based on Finnish media texts, and therefore, the identified categories are interpreted in this specific cultural context. Originality/value The current semiotic analysis adds to the existing food consumption research by shedding light on the cultural barriers that make something edible or inedible. By so doing, the findings present a more nuanced and dynamic understanding of the horse as a special kind of meat animal and the justifications for eating horsemeat. Consequently, the findings offer new insights concerning changing food consumption behaviours into a more sustainable direction, pointing out the hidden meanings that influence this process.

scholarly journals Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

2018 ◽  
Vol 19 (9) ◽  
pp. 2516 ◽  
Author(s):  
Ewelina Piktel ◽  
Ilya Levental ◽  
Bonita Durnaś ◽  
Paul Janmey ◽  
Robert Bucki
Keyword(s):  
Therapeutic Target ◽  
Animal Studies ◽  
Recent Progress ◽  
Mechanisms Of Action ◽  
Current Data ◽  
Clinical Use ◽  
Plasma Gelsolin ◽  
Beneficial Effects ◽  
Potential Biomarker ◽  
Efficacy Of Treatment

Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

scholarly journals Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins

Blood ◽  
2013 ◽  
Vol 121 (8) ◽  
pp. 1276-1284 ◽  
Author(s):  
Dominik J. Schaer ◽  
Paul W. Buehler ◽  
Abdu I. Alayash ◽  
John D. Belcher ◽  
Gregory M. Vercellotti
Keyword(s):  
Animal Studies ◽  
Molecular Characteristics ◽  
Molecular Signaling ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Free Hemoglobin ◽  
Extravascular Space ◽  
Disease States ◽  
Critical Issues ◽  
Rbc Transfusion

Abstract Hemolysis occurs in many hematologic and nonhematologic diseases. Extracellular hemoglobin (Hb) has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release, and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin (Hp) product in Japan and more recent preclinical animal studies suggest that the natural Hb and the hemin-scavenger proteins Hp and hemopexin have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as RBC transfusion, sickle cell disease, sepsis, and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma–derived Hp and hemopexin as therapeutics for patients with excessive intravascular hemolysis.

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