Transitioning from Oxime to the Next Potential Organophosphorus Poisoning Therapy Using Enzymes

For years, organophosphorus poisoning has been a major concern of health problems throughout the world. An estimated 200,000 acute pesticide poisoning deaths occur each year, many in developing countries. Apart from the agricultural pesticide poisoning, terrorists have used these organophosphorus compounds to attack civilian populations in some countries. Recent misuses of sarin in the Syrian conflict had been reported in 2018. Since the 1950s, the therapy to overcome this health problem is to utilize a reactivator to reactivate the inhibited acetylcholinesterase by these organophosphorus compounds. However, many questions remain unanswered regarding the efficacy and toxicity of this reactivator. Pralidoxime, MMB-4, TMB-4, obidoxime, and HI-6 are the examples of the established oximes, yet they are of insufficient effectiveness in some poisonings and only a limited spectrum of the different nerve agents and pesticides are being covered. Alternatively, an option in the treatment of organophosphorus poisoning that has been explored is through the use of enzyme therapy. Organophosphorus hydrolases are a group of enzymes that look promising for detoxifying organophosphorus compounds and have recently gained much interest. These enzymes have demonstrated remarkable protective and antidotal value against some different organophosphorus compounds in vivo in animal models. Apart from that, enzyme treatments have also been applied for decontamination purposes. In this review, the restrictions and obstacles in the therapeutic development of oximes, along with the new strategies to overcome the problems, are discussed. The emerging interest in enzyme treatment with its advantages and disadvantages is described as well.

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Enzyme-based nanocomplexes and their construction for detoxification of organophosphorus compounds

ORGANOPHOSPHORUS NEUROTOXINS ◽

10.29039/53_361-379 ◽

2020 ◽

pp. 361-379

Author(s):

Elena Efremenko ◽

Il'ya Lyagin ◽

Aslanli Aslanli

Keyword(s):

Immune Response ◽

Human Body ◽

Organophosphorus Compounds ◽

The Body ◽

Chemical Methods ◽

Advantages And Disadvantages ◽

Main Challenge ◽

Activity Of Enzymes ◽

Biological Methods

Organophosphorus compounds (OPC) pose a serious threat, as they can have a neurotoxic effect on the human body, even death. In this regard, the main challenge of our times is the search for effective ways of degradation of OPC. In this case, preference is given to biological methods of OPC detoxification, which do not require the use of harsh chemical methods of degradation and are suitable for in vivo use. One of such methods is the use of biocatalysts — enzymes capable of hydrolyzing OPC. To stabilize the activity of enzymes, as well as leveling a possible immune response from the body when used in vivo, various modification methods are used, such as nanocapsulation, the formation of enzymepolyelectrolyte complexes, immobilization of the enzyme on various functionalized carriers, etc. The chapter contains the information on examples of such biocatalysts, discussion of their advantages and disadvantages.

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The Effect of Alimentary Hyperlipemia on Thrombolysis in vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654493 ◽

1960 ◽

Vol 04 (02) ◽

pp. 149-166 ◽

Cited By ~ 5

Author(s):

Nils U. Bang ◽

Eugene E. Cliffton

Keyword(s):

Fibrinolytic Activity ◽

Fibrinolytic Enzyme ◽

Enzyme Treatment ◽

Enzyme Therapy ◽

Fasting State ◽

Fatty Meal ◽

Complete Dissolution ◽

Blood Samples ◽

Specific Inhibitors

Summary1. The effect of a standard, potent fibrinolytic enzyme therapy has been compared in fasting and lipemic dogs.2. The standard fibrinolytic regimen resulted in the complete dissolution of all clots produced experimentally in the fasting state in 10 dogs.3. Clots formed during alimentary lipemia exhibited a markedly increased resistance to the standard fibrinolytic regimen in 6 dogs.4. An increase in anti plasmin fibrinolytic titer with concomitant decrease in spontaneous fibrinolytic activity was observed in 15 dogs following the administration of a fatty meal. No difference in fibrinolytic activity and APF titer was demonstrable in fasting and lipemic blood samples obtained during fibrinolytic enzyme treatment.5. The possibility of the presence of specific inhibitors against the fibrinolytic enzyme in clots formed during lipemia has been investigated and the evidence to support this theory is discussed.

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PERFUSION OF OVARIES IN VITRO AND IN VIVO

Acta Endocrinologica ◽

10.1530/acta.0.069s285 ◽

1972 ◽

Vol 68 (2_Supplb) ◽

pp. S285-S309 ◽

Cited By ~ 5

Author(s):

Kurt Ahrén ◽

Per Olof Janson ◽

Gunnar Selstam

Keyword(s):

Perfusion System ◽

Perfusion Technique ◽

Preliminary Results ◽

Advantages And Disadvantages

ABSTRACT This paper discusses in vivo and in vitro ovarian perfusion systems described so far in the literature. The interest is not focussed primarily on the results of these studies but rather on the advantages and disadvantages of the techniques and methods used. Another part of the paper summarizes the points which are most important, in our opinion, to take into consideration when developing an in vitro perfusion technique of the ovary. The last part of the paper gives a description of and some preliminary results from an in vitro perfusion system of the rabbit ovary which is under development in this laboratory.

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Implantable neural interfaces

10.1093/oso/9780199674923.003.0050 ◽

2018 ◽

Author(s):

Stefano Vassanelli

Keyword(s):

Brain Function ◽

Large Scale ◽

Ionic Channels ◽

Patch Clamp Technique ◽

Advantages And Disadvantages ◽

Optogenetic Stimulation ◽

Physical Interfaces ◽

The Brain

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.

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Biomechanics of Neutrophil Tethers

Life ◽

10.3390/life11060515 ◽

2021 ◽

Vol 11 (6) ◽

pp. 515

Author(s):

Andrea Cugno ◽

Alex Marki ◽

Klaus Ley

Keyword(s):

Cell Activation ◽

Optical Trap ◽

Biomechanical Properties ◽

Force Microscopy ◽

Advantages And Disadvantages ◽

Atomic Force ◽

Microfluidic Flow ◽

Biomembrane Force Probe ◽

Membrane Reservoir

Leukocytes, including neutrophils, which are propelled by blood flow, can roll on inflamed endothelium using transient bonds between selectins and their ligands, and integrins and their ligands. When such receptor–ligand bonds last long enough, the leukocyte microvilli become extended and eventually form thin, 20 m long tethers. Tether formation can be observed in blood vessels in vivo and in microfluidic flow chambers. Tethers can also be extracted using micropipette aspiration, biomembrane force probe, optical trap, or atomic force microscopy approaches. Here, we review the biomechanical properties of leukocyte tethers as gleaned from such measurements and discuss the advantages and disadvantages of each approach. We also review and discuss viscoelastic models that describe the dependence of tether formation on time, force, rate of loading, and cell activation. We close by emphasizing the need to combine experimental observations with quantitative models and computer simulations to understand how tether formation is affected by membrane tension, membrane reservoir, and interactions of the membrane with the cytoskeleton.

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Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

Methods and Protocols ◽

10.3390/mps4010022 ◽

2021 ◽

Vol 4 (1) ◽

pp. 22

Author(s):

Mrinmoyee Majumder ◽

Viswanathan Palanisamy

Keyword(s):

Gene Expression ◽

Protein Interactions ◽

Rna Binding ◽

Rna Binding Proteins ◽

Expression Patterns ◽

Control Of Gene Expression ◽

Regulatory Pathways ◽

Advantages And Disadvantages ◽

Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

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Scanning and Actuation Techniques for Cantilever-Based Fiber Optic Endoscopic Scanners—A Review

Sensors ◽

10.3390/s21010251 ◽

2021 ◽

Vol 21 (1) ◽

pp. 251

Author(s):

Mandeep Kaur ◽

Pierre M. Lane ◽

Carlo Menon

Keyword(s):

Micro Electro Mechanical System ◽

Modern Medicine ◽

Image Resolution ◽

Optical Fields ◽

Scanning Method ◽

Advantages And Disadvantages ◽

Image Area ◽

Technical Advances ◽

Scanning Fiber

Endoscopes are used routinely in modern medicine for in-vivo imaging of luminal organs. Technical advances in the micro-electro-mechanical system (MEMS) and optical fields have enabled the further miniaturization of endoscopes, resulting in the ability to image previously inaccessible small-caliber luminal organs, enabling the early detection of lesions and other abnormalities in these tissues. The development of scanning fiber endoscopes supports the fabrication of small cantilever-based imaging devices without compromising the image resolution. The size of an endoscope is highly dependent on the actuation and scanning method used to illuminate the target image area. Different actuation methods used in the design of small-sized cantilever-based endoscopes are reviewed in this paper along with their working principles, advantages and disadvantages, generated scanning patterns, and applications.

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In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers

Polymers ◽

10.3390/polym13142348 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2348

Author(s):

Leon Riehakainen ◽

Chiara Cavallini ◽

Paolo Armanetti ◽

Daniele Panetta ◽

Davide Caramella ◽

...

Keyword(s):

Imaging Modality ◽

Imaging Techniques ◽

Special Focus ◽

Tissue Remodelling ◽

Biodegradable Implant ◽

Advantages And Disadvantages ◽

Non Invasive ◽

Positron Emission ◽

Longitudinal Imaging

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.

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Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates

Cells ◽

10.3390/cells10040914 ◽

2021 ◽

Vol 10 (4) ◽

pp. 914

Author(s):

Melanie V. Brady ◽

Flora M. Vaccarino

Keyword(s):

Stem Cell ◽

Human Brain ◽

Human Development ◽

Disease Modeling ◽

Model Systems ◽

Advantages And Disadvantages ◽

Technical Ability ◽

Cellular Phenotypes

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.

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Animal Models of Colorectal Cancer: From Spontaneous to Genetically Engineered Models and Their Applications

Veterinary Sciences ◽

10.3390/vetsci8040059 ◽

2021 ◽

Vol 8 (4) ◽

pp. 59

Author(s):

Elisabete Nascimento-Gonçalves ◽

Bruno A.L. Mendes ◽

Rita Silva-Reis ◽

Ana I. Faustino-Rocha ◽

Adelina Gama ◽

...

Keyword(s):

Colorectal Cancer ◽

Animal Models ◽

Cancer Progression ◽

Social Impact ◽

Genetically Engineered ◽

In Vivo Studies ◽

Gastrointestinal Malignancies ◽

Advantages And Disadvantages ◽

Colon Cancer Progression

Colorectal cancer is one of the most common gastrointestinal malignancies in humans, affecting approximately 1.8 million people worldwide. This disease has a major social impact and high treatment costs. Animal models allow us to understand and follow the colon cancer progression; thus, in vivo studies are essential to improve and discover new ways of prevention and treatment. Dietary natural products have been under investigation for better and natural prevention, envisioning to show their potential. This manuscript intends to provide the readers a review of rodent colorectal cancer models available in the literature, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds’ effects on colorectal cancer.

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