-
Ugeskrift For Laeger Oct 2017The main purpose of this study is to review the function of nitric oxide during sepsis and septic shock. Futhermore, the study reviews the various physiological... (Review)
Review
The main purpose of this study is to review the function of nitric oxide during sepsis and septic shock. Futhermore, the study reviews the various physiological functions of nitric oxide in the human body, and how these functions can and have been used clinically. Nitric oxide plays an important role during septic shock in contributing to development of hypotension, multiorgan failure and lack of response to pressor therapy. Elevated concentrations of nitric oxide in both circulation and expiratory air have been found in hu-mans and animals during sepsis and septic shock. Further-more, studies show that nictric oxide plays an important role in the immune system. The physiological effect of nitric oxide has been used in various treatments.
Topics: Hemodynamics; Humans; Lung; Nitric Oxide; Sepsis; Vasodilator Agents
PubMed: 29084619
DOI: No ID Found -
Immunology Jul 2001Nitric oxide (NO) is a free radical which has important effects on bone cell function. The endothelial isoform of nitric oxide synthase (eNOS) is widely expressed in... (Review)
Review
Nitric oxide (NO) is a free radical which has important effects on bone cell function. The endothelial isoform of nitric oxide synthase (eNOS) is widely expressed in bone on a constitutive basis, whereas inducible NOS is only expressed in response to inflammatory stimuli. It is currently unclear whether neuronal NOS is expressed by bone cells. Pro-inflammatory cytokines such as IL-1 and TNF cause activation of the iNOS pathway in bone cells and NO derived from this pathway potentiates cytokine and inflammation induced bone loss. These actions of NO are relevant to the pathogenesis of osteoporosis in inflammatory diseases such as rheumatoid arthritis, which are characterized by increased NO production and cytokine activation. Interferon gamma is a particularly potent stimulator of NO production when combined with other cytokines, causing very high concentrations of NO to be produced. These high levels of NO inhibit bone resorption and formation and may act to suppress bone turnover in severe inflammation. The eNOS isoform seems to play a key role in regulating osteoblast activity and bone formation since eNOS knockout mice have osteoporosis due to defective bone formation. Other studies have indicated that the NO derived from the eNOS pathway acts as a mediator of the effects of oestrogen in bone. eNOS also mediates the effects of mechanical loading on the skeleton where it acts along with prostaglandins, to promote bone formation and suppress bone resorption. Pharmacological NO donors have been shown to increase bone mass in experimental animals and preliminary evidence suggests that these agents may also influence bone turnover in man. These data indicate that the L-arginine/NO pathway represents a novel target for therapeutic intervention in the prevention and treatment of bone diseases.
Topics: Arthritis, Rheumatoid; Bone Development; Bone Resorption; Bone and Bones; Estrogens; Humans; Nitric Oxide
PubMed: 11454054
DOI: 10.1046/j.1365-2567.2001.01261.x -
Sensors (Basel, Switzerland) Nov 2022High equipment cost is a significant entry barrier to research for small organizations in developing solutions to air pollution problems. Low-cost electrochemical...
High equipment cost is a significant entry barrier to research for small organizations in developing solutions to air pollution problems. Low-cost electrochemical sensors show sensitivity at parts-per-billion by volume mixing ratios but are subject to variation due to changing environmental conditions, in particular temperature. In this study, we demonstrate a low-cost Internet of Things (IoT)-based sensor system for nitric oxide analysis. The sensor system used a four-electrode electrochemical sensor exposed to a series of isothermal/isohume conditions. When deployed under these conditions, stable baseline responses were achieved, in contrast to ambient air conditions where temperature and humidity conditions may be variable. The interrelationship between working and auxiliary electrodes was linear within an environmental envelope of 20-40 °C and 30-80% relative humidity, with correlation coefficients from 0.9980 to 0.9999 when measured under isothermal/isohume conditions. These data enabled the determination of surface functions that describe the working to auxiliary electrode offsets and calibration curve gradients and intercepts. The linear and reproducible nature of individual calibration curves for stepwise nitric oxide (NO) additions under isothermal/isohume environments suggests the suitability of these sensors for applications aside from their role in air quality monitoring. Such applications would include nitric oxide kinetic studies for atmospheric applications or measurement of the potential biocatalytic activity of nitric oxide consuming enzymes in biocatalytic coatings, both of which currently employ high-capital-cost chemiluminescence detectors.
Topics: Humidity; Temperature; Nitric Oxide; Kinetics; Air Pollution
PubMed: 36433609
DOI: 10.3390/s22229013 -
Journal of Chemical Neuroanatomy Jun 1996Derangements in glutamate neurotransmission have been implicated in several neurodegenerative disorders including, stroke, epilepsy, Huntington's disease, Alzheimer's... (Review)
Review
Derangements in glutamate neurotransmission have been implicated in several neurodegenerative disorders including, stroke, epilepsy, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). Activation of the N-methyl-D-aspartate (NMDA) receptor subtype of glutamate receptors results in the influx of calcium which binds calmodulin and activates neuronal nitric oxide synthase (nNOS), to convent L-arginine to citrulline and nitric oxide (NO). NO has many roles in the central nervous system as a messenger molecule, however, when generated in excess NO can be neurotoxic. Excess NO is in part responsible for glutamate neurotoxicity in primary neuronal cell culture and in animal models of stroke. It is likely that most of the neurotoxic actions of NO are mediated by peroxynitrite (ONOO-), the reaction product from NO and superoxide anion. In pathologic conditions, peroxynitrite and oxygen free radicals can be generated in excess of a cell antioxidant capacity resulting in severe damage to cellular constituents including proteins, DNA and lipids. The inherent biochemical and physiological characteristics of the brain, including high lipid concentrations and energy requirements, make it particularly susceptible to free radical and oxidant mediated insult. Increasing evidence indicates that many neurologic disorders may have components of free radical and oxidative stress induced injury.
Topics: Animals; Humans; Neurotoxins; Nitric Oxide
PubMed: 8811421
DOI: 10.1016/0891-0618(96)00148-2 -
Photochemistry and Photobiology May 2020As an antitumor modality based on sensitizer photoexcitation by tumor-directed light, photodynamic therapy (PDT) has the advantage of being site-specific compared with... (Review)
Review
As an antitumor modality based on sensitizer photoexcitation by tumor-directed light, photodynamic therapy (PDT) has the advantage of being site-specific compared with conventional chemotherapy or radiotherapy. Like these other therapies, however, PDT is often limited by pre-existing or acquired resistance. One type of resistance, discovered in the author's laboratory, involves nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) in tumor cells. Using human breast, prostate and brain cancer cell lines, we have shown that iNOS is dramatically upregulated after a moderate PDT challenge sensitized by 5-aminolevulinic acid-induced protoporphyrin IX. The elevated NO not only elicited a greater resistance to cell photokilling, but also an increase in the growth and migration/invasion rate of surviving cells. Greater iNOS/NO-based resistance was also demonstrated at the in vivo level using a breast tumor xenograft model. More recent studies have shown that NO from PDT-targeted cells can stimulate a progrowth/promigration response in non-targeted bystander cells. These novel effects of NO, their negative impact on PDT efficacy and possible mitigation thereof by anti-iNOS/NO pharmacologic agents will be discussed.
Topics: Animals; Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; Nitric Oxide; Nitric Oxide Synthase Type II; Photochemotherapy; Photosensitizing Agents
PubMed: 31545517
DOI: 10.1111/php.13163 -
Plant, Cell & Environment Apr 2017Abiotic stress is one of the main threats affecting crop growth and production. An understanding of the molecular mechanisms that underpin plant responses against... (Review)
Review
Abiotic stress is one of the main threats affecting crop growth and production. An understanding of the molecular mechanisms that underpin plant responses against environmental insults will be crucial to help guide the rational design of crop plants to counter these challenges. A key feature during abiotic stress is the production of nitric oxide (NO), an important concentration dependent, redox-related signalling molecule. NO can directly or indirectly interact with a wide range of targets leading to the modulation of protein function and the reprogramming of gene expression. The transfer of NO bioactivity can occur through a variety of potential mechanisms but chief among these is S-nitrosylation, a prototypic, redox-based, post-translational modification. However, little is known about this pivotal molecular amendment in the regulation of abiotic stress signalling. Here, we describe the emerging knowledge concerning the function of NO and S-nitrosylation during plant responses to abiotic stress.
Topics: Models, Biological; Nitric Oxide; Plants; Protein Processing, Post-Translational; Stress, Physiological; Temperature
PubMed: 26754426
DOI: 10.1111/pce.12707 -
Molecules (Basel, Switzerland) Dec 2021Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure... (Review)
Review
Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure (IOP) lowering is the most effective way to slow disease progression and prevent blindness. Among the ocular hypotensive drugs currently in use, only a couple act on the conventional outflow system, which is the main pathway for aqueous humor outflow and the major lesion site resulting in ocular hypertension. Nitric oxide (NO) is a commendable new class of glaucoma drugs that acts on the conventional outflow pathway. An increasing number of nitric oxide donors have been developed for glaucoma and ocular hypertension treatment. Here, we will review how NO lowers IOP and the types of nitric oxide donors that have been developed. And a brief analysis of the advantages and challenges associated with the application will be made. The literature used in this review is based on Pubmed database search using 'nitric oxide' and 'glaucoma' as key words.
Topics: Animals; Antihypertensive Agents; Glaucoma; Humans; Intraocular Pressure; Nitric Oxide; Nitric Oxide Donors; Ocular Hypertension
PubMed: 34885889
DOI: 10.3390/molecules26237306 -
American Journal of Physiology. Lung... Mar 2015Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitter molecules important in numerous physiological and pathological processes. Although these molecules were... (Review)
Review
Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitter molecules important in numerous physiological and pathological processes. Although these molecules were first known as environmental toxicants, it is now evident that that they are intricately involved in diverse cellular functions with impact on numerous physiological and pathogenic processes. NO and H2S share some common characteristics but also have unique chemical properties that suggest potential complementary interactions between the two in affecting cellular biochemistry and metabolism. Central among these is the interactions between NO, H2S, and thiols that constitute new ways to regulate protein function, signaling, and cellular responses. In this review, we discuss fundamental biochemical principals, molecular functions, measurement methods, and the pathophysiological relevance of NO and H2S.
Topics: Animals; Humans; Hydrogen Sulfide; Lung Diseases; Models, Biological; Nitric Oxide; Nitric Oxide Donors; Nitrites
PubMed: 25550314
DOI: 10.1152/ajplung.00327.2014 -
Critical Care (London, England) Mar 2017
Topics: Acute Kidney Injury; Humans; Nitric Oxide; Respiratory Distress Syndrome
PubMed: 28363282
DOI: 10.1186/s13054-017-1651-z -
Journal of Physiology and Pharmacology... Dec 2003Nitric oxide (NO) and reactive oxygen species exert multiple modulating effects on inflammation and play a key role in the regulation of immune responses. They affect... (Review)
Review
Nitric oxide (NO) and reactive oxygen species exert multiple modulating effects on inflammation and play a key role in the regulation of immune responses. They affect virtually every step of the development of inflammation. Low concentrations of nitric oxide produced by constitutive and neuronal nitric oxide synthases inhibit adhesion molecule expression, cytokine and chemokine synthesis and leukocyte adhesion and transmigration. Large amounts of NO, generated primarily by iNOS can be toxic and pro-inflammatory. Actions of nitric oxide are however not dependent primarily on the enzymatic source, but rather on the cellular context, NO concentration (dependent on the distance from NO source) and initial priming of immune cells. These observations may explain difficulties in determining the exact role of NO in Th1 and Th2 lymphocyte balance in normal immune responses and in allergic disease. Similarly superoxide anion produced by NAD(P)H oxidases present in all cell types participating in inflammation (leukocytes, endothelial and other vascular cells etc) may lead to toxic effects, when produced at high levels during oxidative burst, but may also modulate inflammation in a far more discrete way, when continuously produced at low levels by NOXs (non-phagocytic oxidases). The effects of both nitric oxide and superoxide in immune regulation are exerted through multiple mechanisms, which include interaction with cell signalling systems like cGMP, cAMP, G-protein, JAK/STAT or MAPK dependent signal transduction pathways. They may also lead to modification of transcription factors activity and in this way modulate the expression of multiple other mediators of inflammation. Moreover genetic polymorphisms exist within genes encoding enzymes producing both NO and superoxide. The potential role of these polymorphisms in inflammation and susceptibility to infection is discussed. Along with studies showing increasing role of NO and free radicals in mediating inflammatory responses drugs which interfere with these systems are being introduced in the treatment of inflammation. These include statins, angiotensin receptor blockers, NAD(P)H oxidase inhibitors, NO-aspirin and others. In conclusion in this mini-review we discuss the mechanisms of nitric oxide and superoxide dependent modulation of inflammatory reactions in experimental animals and humans. We also discuss potential roles of nitric oxide as a mediator of allergic inflammation.
Topics: Animals; Humans; Inflammation; Inflammation Mediators; Models, Biological; Nitric Oxide; Signal Transduction; Superoxides
PubMed: 14726604
DOI: No ID Found