scholarly journals General principles and escalation options of immunotherapy in autoantibody-associated disorders of the CNS

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ilya Ayzenberg ◽  
Simon Faissner ◽  
Laura Tomaske ◽  
Daniel Richter ◽  
Volker Behrendt ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Treatment Response ◽  
Neuronal Loss ◽  
Therapeutic Approaches ◽  
Antigen Stimulation ◽  
Research Fields ◽  
Clinical Presentations ◽  
Wide Range ◽  
Intracellular Antigen ◽  
Tumor Management

Abstract Autoimmune diseases associated with antineuronal and antiglial autoantibodies (Abs) is one of the most rapidly expanding research fields in clinical neuroimmunology, with more than 30 autoantibodies described so far. Being associated with a wide range of clinical presentations these syndromes can be diagnostically challenging. Surface or intracellular antigen localizations are crucial for the treatment response and outcome. In the latter Abs are mostly of paraneoplastic cause and tumor management should be performed as soon as possible in order to stop peripheral antigen stimulation. Immunotherapy should be started early in both groups, before irreversible neuronal loss occurs. Despite serious prognosis, aggressive therapeutic approaches can be effective in many cases. In this article we review main pathogenic mechanisms leading to Abs-related syndromes and describe standard as well as emerging strategies of immunotherapy, including tocilizumab and bortezomib. Several special therapeutic approaches will be illustrated by clinical cases recently treated in our department.

scholarly journals Evaluation of Therapeutic Approaches for the Treatment of Spironucleus muris in Mice

2021 ◽  
Author(s):  
George B Voros ◽  
Robert V Blair ◽  
David D Andrews ◽  
Georgina L Dobek
Keyword(s):  
Gastrointestinal Tract ◽  
Laboratory Animal ◽  
Therapeutic Approaches ◽  
Water Control ◽  
Research Results ◽  
Treatment Groups ◽  
Clinical Presentations ◽  
Wide Range ◽  
Histopathologic Analysis ◽  
Giardia Muris

Spironucleus muris is an intestinal protozoal pathogen that can infect various species of rodents. The infection can have a wide range of clinical presentations, from no signs of disease to death. In addition, this pathogen can adversely affect research results, especially immunologic and gastrointestinal studies. For these reasons, institutions may exclude Spironucleus muris. However, despite rigorous efforts to keep this pathogen out, it can be common in rodent colonies. The current recommendedapproach to eradicating this pathogen is by testing and culling positive animals. A similar organism, Giardia muris, has been effectively eliminated by using chemotherapeutics. Therefore, the objective of this study was to determine whether S. muris is also susceptible to chemotherapeutics. Naturally infected mice were randomized to treatment groups after confirmation of positive infection via PCR. Mice received either metronidazole, fenbendazole, a combination of metronidazole-fenbendazole,or acidified water (control) treatments for a period of 4 wk. Each week fecal testing of S. muris was performed via PCR to evaluate the effectiveness of the treatments. At the end of the 4 wk period, mice were euthanized via CO2inhalation and segments of the proximal gastrointestinal tract were submitted for histopathologic analysis. Treatment with metronidazole or fenbendazole alone or in combination, failed to clear S. muris infected mice. After 4 wk of treatment, none of the mice given fenbendazole via sucralose medicated gel were positive by either PCR or histopathology; however, this finding is most likelydue to intermittent shedding rather than chemotherapeutic success. Therefore, the recommendation remains to test-and-cull or rederive mice as necessary to eliminate S. muris from laboratory animal facilities.

scholarly journals Methods Used and Application of the Mouse Grimace Scale in Biomedical Research 10 Years On: A Scoping Review

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Biomedical Research ◽  
Scoping Review ◽  
Facial Features ◽  
Inclusion Criteria ◽  
Academic Literature ◽  
Research Fields ◽  
Neuroscience Research ◽  
Wide Range

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.

scholarly journals Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7302
Author(s):  
Bryan Latrell Holloman ◽  
Mitzi Nagarkatti ◽  
Prakash Nagarkatti
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Cannabinoid Receptors ◽  
T Regulatory Cells ◽  
Neurological Diseases ◽  
Suppressor Cells ◽  
The Body ◽  
New Class ◽  
Wide Range ◽  
Clinical Disorders

Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative. Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.

scholarly journals Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy

2019 ◽  
Vol 122 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Adrian L. Harris
Keyword(s):  
Metabolic Pathways ◽  
Trial Design ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Therapeutic Approaches ◽  
Preclinical Models ◽  
Wide Range ◽  
Patient Studies

AbstractCancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.

scholarly journals Cycle and flow trusses in directed networks

2016 ◽  
Vol 3 (11) ◽  
pp. 160270 ◽  
Author(s):  
Taro Takaguchi ◽  
Yuichi Yoshida
Keyword(s):  
Truss Structures ◽  
Directed Network ◽  
Unified Framework ◽  
Directed Networks ◽  
Research Fields ◽  
Wide Range ◽  
Definition Of ◽  
Information Finding ◽  
Empirical Networks ◽  
Module Structures

When we represent real-world systems as networks, the directions of links often convey valuable information. Finding module structures that respect link directions is one of the most important tasks for analysing directed networks. Although many notions of a directed module have been proposed, no consensus has been reached. This lack of consensus results partly because there might exist distinct types of modules in a single directed network, whereas most previous studies focused on an independent criterion for modules. To address this issue, we propose a generic notion of the so-called truss structures in directed networks. Our definition of truss is able to extract two distinct types of trusses, named the cycle truss and the flow truss, from a unified framework. By applying the method for finding trusses to empirical networks obtained from a wide range of research fields, we find that most real networks contain both cycle and flow trusses. In addition, the abundance of (and the overlap between) the two types of trusses may be useful to characterize module structures in a wide variety of empirical networks. Our findings shed light on the importance of simultaneously considering different types of modules in directed networks.

Compression neuropathies of the forearm: anatomy, clinical features and management

2021 ◽  
pp. 1-10
Author(s):  
Alexander Scarborough ◽  
Robert J MacFarlane ◽  
Michail Klontzas ◽  
Rui Zhou ◽  
Mohammad Waseem
Keyword(s):  
Peripheral Nerve ◽  
Brachial Plexus ◽  
Upper Limb ◽  
Peripheral Nerves ◽  
Clinical Presentation ◽  
Permanent Damage ◽  
Peripheral Nerve Lesions ◽  
Clinical Presentations ◽  
Wide Range ◽  
Prompt Diagnosis

The upper limb consists of four major parts: a girdle formed by the clavicle and scapula, the arm, the forearm and the hand. Peripheral nerve lesions of the upper limb are divided into lesions of the brachial plexus or the nerves arising from it. Lesions of the nerves arising from the brachial plexus are further divided into upper (proximal) or lower (distal) lesions based on their location. Peripheral nerves in the forearm can be compressed in various locations and by a wide range of pathologies. A thorough understanding of the anatomy and clinical presentations of these compression neuropathies can lead to prompt diagnosis and management, preventing possible permanent damage. This article discusses the aetiology, anatomy, clinical presentation and surgical management of compressive neuropathies of the upper limb.

scholarly journals B Cell Metabolism and Autophagy in Autoimmunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Iwan G. A. Raza ◽  
Alexander J. Clarke
Keyword(s):  
B Cells ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Antigen Presentation ◽  
Functional Properties ◽  
Cell Metabolism ◽  
Metabolic Phenotype ◽  
Therapeutic Approaches ◽  
Treatment Target ◽  
Development And Differentiation

B cells are central to the pathogenesis of multiple autoimmune diseases, through antigen presentation, cytokine secretion, and the production of autoantibodies. During development and differentiation, B cells undergo drastic changes in their physiology. It is emerging that these are accompanied by equally significant shifts in metabolic phenotype, which may themselves also drive and enforce the functional properties of the cell. The dysfunction of B cells during autoimmunity is characterised by the breaching of tolerogenic checkpoints, and there is developing evidence that the metabolic state of B cells may contribute to this. Determining the metabolic phenotype of B cells in autoimmunity is an area of active study, and is important because intervention by metabolism-altering therapeutic approaches may represent an attractive treatment target.

scholarly journals MTEP, a Selective mGluR5 Antagonist, Had a Neuroprotective Effect but Did Not Prevent the Development of Spontaneous Recurrent Seizures and Behavioral Comorbidities in the Rat Lithium–Pilocarpine Model of Epilepsy

2022 ◽  
Vol 23 (1) ◽  
pp. 497
Author(s):  
Alexandra V. Dyomina ◽  
Anna A. Kovalenko ◽  
Maria V. Zakharova ◽  
Tatiana Yu. Postnikova ◽  
Alexandra V. Griflyuk ◽  
...  
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Excitatory Amino Acid ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Brain Diseases ◽  
Excitatory Amino Acid Transporter ◽  
Wide Range ◽  
Pilocarpine Model ◽  
Mglur5 Antagonist ◽  
Behavioral Impairments

Metabotropic glutamate receptors (mGluRs) are expressed predominantly on neurons and glial cells and are involved in the modulation of a wide range of signal transduction cascades. Therefore, different subtypes of mGluRs are considered a promising target for the treatment of various brain diseases. Previous studies have demonstrated the seizure-induced upregulation of mGluR5; however, its functional significance is still unclear. In the present study, we aimed to clarify the effect of treatment with the selective mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that the administration of MTEP during the latent phase of the model did not improve survival, prevent the development of epilepsy, or attenuate its manifestations in rats. However, MTEP treatment completely prevented neuronal loss and partially attenuated astrogliosis in the hippocampus. An increase in excitatory amino acid transporter 2 expression, which has been detected in treated rats, may prevent excitotoxicity and be a potential mechanism of neuroprotection. We also found that MTEP administration did not prevent the behavioral comorbidities such as depressive-like behavior, motor hyperactivity, reduction of exploratory behavior, and cognitive impairments typical in the lithium–pilocarpine model. Thus, despite the distinct neuroprotective effect, the MTEP treatment was ineffective in preventing epilepsy.

scholarly journals Size matters: Size Dependency of Gold Nanoparticles Interacting with Model Membranes

2019 ◽  
Author(s):  
Claudia Contini ◽  
James W. Hindley ◽  
Tom Macdonald ◽  
Joseph Barritt ◽  
Oscar Ces ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Lipid Bilayers ◽  
Lipid Membrane ◽  
Rapid Development ◽  
Membrane System ◽  
Size Dependent ◽  
Research Fields ◽  
Large Unilamellar Vesicles ◽  
Wide Range ◽  
Experimental Characterisation

<p><b>The rapid development of nanomaterials has led to an increase in the number and variety of engineered nanomaterials (ENMs) in the environment. Gold nanoparticles (AuNPs) are an example of a commonly studied ENM whose highly tailorable properties have generated significant interest through a wide range of research fields. In the present work, we report the first qualitative as well as quantitative experimental characterisation of the AuNP-membrane interaction. We investigate the interactions between citrate-stabilised AuNPs (diameters 5, 10, 25, 35, 50, 60 nm) and large unilamellar vesicles (LUVs) acting as a model membrane system. LUVs were prepared in two different formulations using 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1,2-dileoyl-sn-glycero-3-phosphocholine (DOPC). Our results show that the interaction between AuNPs and LUVs is size dependent; in particular, we reveal the existence of two AuNP’s critical diameters which determine the fate of AuNPs in contact with a lipid membrane. The results provide a new understanding of the size dependent interaction between AuNPs and lipid bilayers of direct relevance to nanotoxicology and to the design of NP vectors.</b></p>

scholarly journals Host-Directed Therapies for Cutaneous Leishmaniasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernanda O. Novais ◽  
Camila Farias Amorim ◽  
Phillip Scott
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Inflammatory Diseases ◽  
Wide Spectrum ◽  
Substantial Evidence ◽  
Novel Approach ◽  
Clinical Presentations ◽  
Wide Range ◽  
Parasite Replication ◽  
Inflammatory Drugs ◽  
Improve Clinical Outcome

Cutaneous leishmaniasis exhibits a wide spectrum of clinical presentations from self-resolving infections to severe chronic disease. Anti-parasitic drugs are often ineffective in the most severe forms of the disease, and in some cases the magnitude of the disease can result from an uncontrolled inflammatory response rather than unrestrained parasite replication. In these patients, host-directed therapies offer a novel approach to improve clinical outcome. Importantly, there are many anti-inflammatory drugs with known safety and efficacy profiles that are currently used for other inflammatory diseases and are readily available to be used for leishmaniasis. However, since leishmaniasis consists of a wide range of clinical entities, mediated by a diverse group of leishmanial species, host-directed therapies will need to be tailored for specific types of leishmaniasis. There is now substantial evidence that host-directed therapies are likely to be beneficial beyond autoimmune diseases and cancer and thus should be an important component in the armamentarium to modulate the severity of cutaneous leishmaniasis.

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