scholarly journals A Neurologist’s Guide to TNF Biology and to the Principles behind the Therapeutic Removal of Excess TNF in Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Ian A. Clark ◽  
Bryce Vissel
Keyword(s):  
Proinflammatory Cytokine ◽  
Physiological Function ◽  
The Body ◽  
Clinical Neurology ◽  
Medical Specialties ◽  
Disease Mechanisms ◽  
The Central Nervous System ◽  
Basic Biology ◽  
Neurological Conditions ◽  
Necrosis Factor

Tumor necrosis factor (TNF) is an ancient and widespread cytokine required in small amounts for much physiological function. Higher concentrations are central to innate immunity, but if unchecked this cytokine orchestrates much chronic and acute disease, both infectious and noninfectious. While being a major proinflammatory cytokine, it also controls homeostasis and plasticity in physiological circumstances. For the last decade or so these principles have been shown to apply to the central nervous system as well as the rest of the body. Nevertheless, whereas this approach has been a major success in treating noncerebral disease, its investigation and potential widespread adoption in chronic neurological conditions has inexplicably stalled since the first open trial almost a decade ago. While neuroscience is closely involved with this approach, clinical neurology appears to be reticent in engaging with what it offers patients. Unfortunately, the basic biology of TNF and its relevance to disease is largely outside the traditions of neurology. The purpose of this review is to facilitate lowering communication barriers between the traditional anatomically based medical specialties through recognition of shared disease mechanisms and thus advance the prospects of a large group of patients with neurodegenerative conditions for whom at present little can be done.

Characteristics of the dynamics of the central nervous system and att ention function in workers of shoe production

2020 ◽  
pp. 64-68
Author(s):  
F. L. Azizova ◽  
U. A. Boltaboev
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Women Workers ◽  
Functional State ◽  
The Body ◽  
Conflict Of Interests ◽  
Professional Groups ◽  
Universal Device ◽  
The Central Nervous System ◽  
Working Day

The features of production factors established at the main workplaces of shoe production are considered. The materials on the results of the study of the functional state of the central nervous system of women workers of shoe production in the dynamics of the working day are presented. The level of functional state of the central nervous system was determined by the speed of visual and auditory-motor reactions, installed using the universal device chronoreflexometer. It was revealed that in the body of workers of shoe production there is an early development of inhibitory processes in the central nervous system, which is expressed in an increase in the number of errors when performing tasks on proofreading tables. It was found that the most pronounced shift s in auditory-motor responses were observed in professional groups, where higher levels of noise were registered in the workplace. The correlation analysis showed a close direct relationship between the growth of mistakes made in the market and the decrease in production. An increase in the time spent on the task indicates the occurrence and growth of production fatigue.Funding. The study had no funding.Conflict of interests. The authors declare no conflict of interests.

Assessment of the Biochemical Status of Workers Manufacturing Ethylbenzene and Styrene

2020 ◽  
pp. 40-43
Author(s):  
RR Galimova ◽  
ET Valeeva ◽  
GV Timasheva ◽  
AB Bakirov
Keyword(s):  
Catalase Activity ◽  
Free Radical Oxidation ◽  
The Body ◽  
Atherogenic Index ◽  
Radical Oxidation ◽  
Professional Groups ◽  
Biochemical Status ◽  
The Central Nervous System ◽  
Hepatic Protein Synthesis ◽  
Increased Activity

Introduction: Production of ethylbenzene and styrene (EBS) is one of the most important stages in organic synthesis. The products have general toxic, hepatotoxic, irritating and narcotic effects on the human body. Severe exposures to EВS can induce pronounced disorders of the central nervous system such as styrene sickness and encephalopathy and of peripheral blood such as leukopenia and lymphocytosis. Materials and methods: We studied homeostasis indices in 376 workers of the main professional groups engaged in the production of EBS including equipment operators, repairmen, and instrumentation and automation fitters. Results: We established an increase in lipid peroxidation by the level of malondialdehyde amid an increase in catalase activity and a decrease in blood retinol and α-tocopherol levels. We also noted an increased activity of indicator enzymes including ALT, AST, GGT, and alkaline phosphatase. Significant changes in lipid metabolism in the form of cholesterolemia, triglyceridemia, a higher atherogenic index, and lower cholesterol of non-atherogenic blood serum lipids demonstrating atherogenic changes in the body were revealed. Conclusions: The earliest prenosological disorders in the body of the examined workers included an impaired hepatic protein synthesis, the development of cytolysis processes and a change in the integrity and functional activity of the liver cell in individuals, an imbalance in the oxidant-antioxidant system, one of the reasons of which was the adverse occupational exposure to hazardous chemicals. An increase in catalase activity is a protective compensatory reaction during the activation of free radical oxidation processes.

Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Glial Cells ◽  
Brain Injuries ◽  
The Body ◽  
The Central Nervous System ◽  
Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders

2020 ◽  
Vol 20 (13) ◽  
pp. 1142-1153 ◽  
Author(s):  
Sreyashi Chandra ◽  
Md. Tanjim Alam ◽  
Jhilik Dey ◽  
Baby C. Pulikkaparambil Sasidharan ◽  
Upasana Ray ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Disorders ◽  
The Body ◽  
Therapeutic Approaches ◽  
Cns Disorders ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Present Understanding ◽  
Lateral Sclerosis

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.

Toughness

2009 ◽  
pp. 536-548
Author(s):  
Richard A. Dienstbier ◽  
Lisa M. Pytlik Zillig
Keyword(s):  
The Body ◽  
Positive Outcomes ◽  
Adaptive Coping ◽  
Dynamic Interactions ◽  
Abstract Level ◽  
The Central Nervous System ◽  
Cortical System ◽  
The Mind ◽  
And Training ◽  
Neuroendocrine Systems

This chapter presents an overview of the concept of toughness, which at the abstract level is about the harmony of physiological systems, and more concretely is about how the body influences the mind. Toughness theory begins with the recognition that there is a “training effect” for neuroendocrine systems. Following a review of the characteristics of interventions and training programs that can promote toughness, the authors present a model in which the effects of toughness are mediated by neuroendocrine systems such as the pituitary-adrenal-cortical system and the central nervous system. The elements of toughness (e.g., having a greater capacity for arousal and energy when needed) are proposed to promote positive outcomes by facilitating the use of adaptive coping strategies and improving emotional stability. Toughness therefore appears to be a promising concept within positive psychology in that it helps to explain how the dynamic interactions between psychological and somatic processes can promote positive outcomes.

scholarly journals The Role of Th17 Response in COVID-19

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1550
Author(s):  
Diana Martonik ◽  
Anna Parfieniuk-Kowerda ◽  
Magdalena Rogalska ◽  
Robert Flisiak
Keyword(s):  
Immune Response ◽  
Treg Cells ◽  
The Body ◽  
System Response ◽  
Th17 Response ◽  
Monocyte Chemoattractant Protein 1 ◽  
Acute Infectious Disease ◽  
Cytokine Cascade ◽  
Necrosis Factor

COVID-19 is an acute infectious disease of the respiratory system caused by infection with the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome Coronavirus 2). Transmission of SARS-CoV-2 infections occurs through droplets and contaminated objects. A rapid and well-coordinated immune system response is the first line of defense in a viral infection. However, a disturbed and over-activated immune response may be counterproductive, causing damage to the body. Severely ill patients hospitalised with COVID-19 exhibit increased levels of many cytokines, including Interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, IL-10, IL-17, granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF). Increasing evidence suggests that Th17 cells play an important role in the pathogenesis of COVID-19, not only by activating cytokine cascade but also by inducing Th2 responses, inhibiting Th1 differentiation and suppressing Treg cells. This review focuses on a Th17 pathway in the course of the immune response in COVID-19, and explores plausible targets for therapeutic intervention.

scholarly journals Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

2021 ◽  
Vol 22 (13) ◽  
pp. 6858
Author(s):  
Fanny Gaudel ◽  
Gaëlle Guiraudie-Capraz ◽  
François Féron
Keyword(s):  
G Proteins ◽  
The Body ◽  
Trace Amines ◽  
Chemical Senses ◽  
Brain Areas ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Human Brains ◽  
The Brain ◽  
Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

scholarly journals Efficacy of Alpinumisoflavone Isolated from Maclura tricuspidata Fruit in Tumor Necrosis Factor-α-Induced Damage of Human Dermal Fibroblasts

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 514
Author(s):  
Sullim Lee ◽  
Giang Do Hoang ◽  
Daeyoung Kim ◽  
Ho Sueb Song ◽  
Sungyoul Choi ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Dermal Fibroblasts ◽  
The Body ◽  
Hazardous Substances ◽  
Human Dermal Fibroblasts ◽  
Cutaneous Lesions ◽  
Matrix Metalloproteinase 1 ◽  
Tnf Α ◽  
Necrosis Factor

The skin is an important organ in the human body that protects the body from environmentally hazardous substances. Reactive oxygen species (ROS) cause inflammatory reactions and degradation of the extracellular matrix leading to skin aging and various cutaneous lesions. This study evaluated the potential of isoflavones isolated from Maclura tricuspidata fruit to prevent TNF-α-induced skin inflammation in normal human dermal fibroblasts (HDFs). It focused on alpinumisoflavone (AIF) that suppressed the accumulation of ROS and nitric oxide (NO) in tumor necrosis factor-alpha (TNF-α)-treated HDFs. AIF inhibited the TNF-α-induced increase in matrix metalloproteinase-1, decreased procollagen I α1, and suppressed pro-inflammatory mediators and pro-inflammatory cytokines, including NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8 that trigger inflammatory responses. AIF inhibited nuclear factor-κB and activating protein 1 mitogen-activated protein kinases that were increased by TNF-α stimulation. These results suggest that AIF may protect skin from aging and various cutaneous lesions.

scholarly journals Monoclonal Antibodies as Neurological Therapeutics

2021 ◽  
Vol 14 (2) ◽  
pp. 92
Author(s):  
Panagiotis Gklinos ◽  
Miranta Papadopoulou ◽  
Vid Stanulovic ◽  
Dimos D. Mitsikostas ◽  
Dimitrios Papadopoulos
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Therapeutic Agents ◽  
Medical Specialties ◽  
Specific Effects ◽  
Different Types ◽  
Neurological Conditions ◽  
Disease Pathways

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases. Untangling the molecular mechanisms of disease allows monoclonal antibodies to block disease pathways accurately and efficiently with exceptional target specificity, minimizing non-specific effects. On the other hand, accumulating experience shows that monoclonal antibodies may carry class-specific and target-associated risks. This article provides an overview of different types of monoclonal antibodies and their characteristics and reviews monoclonal antibodies currently in use or under development for neurological disease.

scholarly journals Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells

2015 ◽  
Vol 89 (23) ◽  
pp. 12118-12130 ◽  
Author(s):  
Ferdinand Roesch ◽  
Léa Richard ◽  
Réjane Rua ◽  
Françoise Porrot ◽  
Nicoletta Casartelli ◽  
...  
Keyword(s):  
Immune Responses ◽  
Proinflammatory Cytokine ◽  
Tumor Necrosis ◽  
Cellular Proteins ◽  
Accessory Protein ◽  
Infected Cells ◽  
Hiv 1 ◽  
Necrosis Factor ◽  
Stimulation Of

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.

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