Histamine: mercurial messenger in the gut

1992 ◽  
Vol 262 (1) ◽  
pp. G1-G13 ◽  
Author(s):  
P. K. Rangachari
Keyword(s):  
Diamine Oxidase ◽  
Multiple Roles ◽  
Pharmacological Agents ◽  
Cellular Targets ◽  
Mucosal Mast Cells ◽  
Intracellular Messengers ◽  
Pathophysiological Role ◽  
H3 Receptors ◽  
Metabolic Transformation ◽  
Inflammatory Processes

This review considers the possibility that histamine functions as a cellular messenger in the gastrointestinal tract. Any biological messenger must be produced, received, and responded to, and must have its actions quickly terminated. Histamine is no exception. Histamine synthesis from L-histidine occurs in enterochromaffin-like cells, mucosal mast cells, and nerves. Histamine release occurs through both antibody-dependent and antibody-independent mechanisms. Released histamine interacts with a variety of cellular targets (epithelial cells, smooth muscle cells, endothelial cells, neurons, and a variety of immunocompetent cells). Occupation of H1, H2, and H3 receptors, defined by pharmacological agents, is transduced by different intracellular messengers (Ca2+, cyclic nucleotides) into diverse effects such as secretion, contraction, or modulation of other secretagogues. The responses to histamine are terminated by at least three different mechanisms: metabolic transformation by the actions of methyltransferase and diamine oxidase, desensitization at the receptor level, and cellular uptake. In addition to its well-documented effects as a mediator of inflammatory processes, histamine may also function as a neuro- and immunoregulator. While a significant pathophysiological role for histamine has been realized since the earliest description of its effects, the availability of newer pharmacological agents has permitted a finer dissection of its "physiological" effects and raised the possibility of multiple roles for histamine.

scholarly journals Reassessing the Role of Intra-Arterial Drug Delivery for Glioblastoma Multiforme Treatment

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Jason A. Ellis ◽  
Matei Banu ◽  
Shaolie S. Hossain ◽  
Rajinder Singh-Moon ◽  
Sean D. Lavine ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Optical Measurements ◽  
Pharmacological Agents ◽  
Cellular Targets ◽  
Therapeutic Landscape ◽  
Rational Drug

Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed.

Evidence on the pathogenic role of auto-antibodies in acute cardiovascular diseases

2013 ◽  
Vol 109 (05) ◽  
pp. 854-868 ◽  
Author(s):  
Federico Carbone ◽  
Alessio Nencioni ◽  
François Mach ◽  
Nicolas Vuilleumier ◽  
Fabrizio Montecucco
Keyword(s):  
Immune Cells ◽  
Atherosclerotic Plaques ◽  
Plaque Vulnerability ◽  
Pathogenic Role ◽  
Pathophysiological Role ◽  
Different Types ◽  
Inflammatory Processes ◽  
Oxidative Processes ◽  
Circulating Autoantibodies

SummaryAtherothrombosis is the major determinant of acute ischaemic cardiovascular events, such as myocardial infarction and stroke. Inflammatory processes have been linked to all phases of atherogenesis In particular, the identification of autoimmunity mediators in the complex microenvironment of chronic inflammation has become the focus of attention in both early and advanced atherogenic processes. Autoantibodies against self-molecules or new epitopes generated by oxidative processes infiltrate atherosclerotic plaques and were shown to modulate the activity of immune cells by binding various types of receptors. However, despite mounting evidence for a pathophysiological role of autoantibodies in atherothrombosis, the clinical relevance for circulating autoantibodies in cardiovascular outcomes is still debated. This review aims at illustrating the mechanisms by which different types of autoantibodies might either promote or repress atherothrombosis and to discuss the clinical studies assessing the role of auto-antibodies as prognostic biomarkers of plaque vulnerability.

scholarly journals The Use of Glial Fibrillary Acidic Protein in First-Tier Assessments of Neurotoxicity

1991 ◽  
Vol 10 (6) ◽  
pp. 719-726 ◽  
Author(s):  
James P. O'Callaghan
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Cell Loss ◽  
Acidic Protein ◽  
Intermediate Filament Protein ◽  
Pharmacological Agents ◽  
Cellular Targets ◽  
Dose Time ◽  
Enhanced Expression ◽  
Second Tier ◽  
Filament Protein

Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes, a subtype of central nervous system glia. The hallmark of this response, often termed “reactive gliosis,” is the enhanced expression of the major intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP). These morphological observations suggest that GFAP may be a useful biochemical indicator of neurotoxicity. To investigate this possibility we have administered prototype neurotoxicants to experimental animals and then assessed the effects of these agents on the tissue content of GFAP, as determined by radioimmunoassay. We found that assays of GFAP reveal dose-, time-, and region-dependent patterns of neurotoxicity at toxicant dosages below those that cause light microscopic evidence of cell loss or damage. No false positives have been seen following exposure to a variety of pharmacological agents. By using regional assessments of GFAP in a first-tier evaluation, it should be possible to localize areas of damage. A second-tier evaluation, using assays of proteins or transmitters associated with cells in the affected region, may reveal the cellular targets of neurotoxicity. This two-tiered approach should serve as a foundation for guiding studies aimed at determining mechanisms of neurotoxicity.

scholarly journals Inflammatory aspects of epileptogenesis: contribution of molecular inflammatory mechanisms

2016 ◽  
Vol 29 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Feyza Alyu ◽  
Miriş Dikmen
Keyword(s):  
Interleukin 1 ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathways ◽  
Pharmacological Agents ◽  
Inflammatory Protein ◽  
Pubmed Database ◽  
Inflammatory Processes ◽  
Inflammatory Proteins ◽  
Genetically Determined

ObjectiveEpilepsy is a chronic neurological disease characterised with seizures. The aetiology of the most generalised epilepsies cannot be explicitly determined and the seizures are pronounced to be genetically determined by disturbances of receptors in central nervous system. Besides, neurotransmitter distributions or other metabolic problems are supposed to involve in epileptogenesis. Lack of adequate data about pharmacological agents that have antiepileptogenic effects point to need of research on this field. Thus, in this review, inflammatory aspects of epileptogenesis has been focussed via considering several concepts like role of immune system, blood–brain barrier and antibody involvement in epileptogenesis.MethodsWe conducted an evidence-based review of the literatures in order to evaluate the possible participation of inflammatory processes to epileptogenesis and also, promising agents which are effective to these processes. We searched PubMed database up to November 2015 with no date restrictions.ResultsIn the present review, 163 appropriate articles were included. Obtained data suggests that inflammatory processes participate to epileptogenesis in several ways like affecting fibroblast growth factor-2 and tropomyosin receptor kinase B signalling pathways, detrimental proinflammatory pathways [such as the interleukin-1 beta (IL-1β)–interleukin-1 receptor type 1 (IL-1R1) system], mammalian target of rapamycin pathway, microglial activities, release of glial inflammatory proteins (such as macrophage inflammatory protein, interleukin 6, C–C motif ligand 2 and IL-1β), adhesion molecules that are suggested to function in signalling pathways between neurons and microglia and also linkage between these molecules and proinflammatory cytokines.ConclusionThe literature research indicated that inflammation is a part of epileptogenesis. For this reason, further studies are necessary for assessing agents that will be effective in clinical use for therapeutic treatment of epileptogenesis.

scholarly journals Zinc in the Brain: Friend or Foe?

2020 ◽  
Vol 21 (23) ◽  
pp. 8941
Author(s):  
Seunghyuk Choi ◽  
Dae Ki Hong ◽  
Bo Young Choi ◽  
Sang Won Suh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metal Ion ◽  
Physiological Role ◽  
Multiple Roles ◽  
Antioxidant Function ◽  
Pathophysiological Role ◽  
The Central Nervous System ◽  
Biological Component ◽  
The Brain

Zinc is a trace metal ion in the central nervous system that plays important biological roles, such as in catalysis, structure, and regulation. It contributes to antioxidant function and the proper functioning of the immune system. In view of these characteristics of zinc, it plays an important role in neurophysiology, which leads to cell growth and cell proliferation. However, after brain disease, excessively released and accumulated zinc ions cause neurotoxic damage to postsynaptic neurons. On the other hand, zinc deficiency induces degeneration and cognitive decline disorders, such as increased neuronal death and decreased learning and memory. Given the importance of balance in this context, zinc is a biological component that plays an important physiological role in the central nervous system, but a pathophysiological role in major neurological disorders. In this review, we focus on the multiple roles of zinc in the brain.

Do neurons have mood and how can it be stabilised?

2011 ◽  
Vol 26 (S2) ◽  
pp. 2050-2050
Author(s):  
L.G. Hranov
Keyword(s):  
Stress Proteins ◽  
Bipolar Affective Disorder ◽  
Mitochondrial Respiratory Chain ◽  
Respiratory Chain Enzyme ◽  
Pharmacological Agents ◽  
Expression Of Genes ◽  
Long Run ◽  
Intracellular Messengers ◽  
Apoptotic Pathways

Polarity of affective tone has taken the role of the core defining feature of bipolar affective disorder (BAD) eclipsing Falret's and Kraepelin's emphasis on cyclicity and recurrence. Yet in many clinical cases polarity is lost in the course of time while cyclic recurrence persists for decades, completely disrupting patients’ lives. That's why true “mood stabilisation” aims not as much at reducing episode severity as at reducing episode number to a minimum.On the neuronal level polarity could be envisaged as interplay between arousal and inhibition due to trans-membrane ion currents, either brief and adaptive or pathologically sustained. Cyclicity and recurrence could arise from permanent deficits in neuronal plasticity and resilience which are to a large extent under genetic control. The “mood stabilising” properties of different pharmacological agents are due to multi-level actions on the intracellular signal transduction pathways affecting the function of Gi and Go proteins, of some intracellular messengers (mioinositol, Bcl-2, ER stress proteins, MARKS, the complex calmodulin-synapsin1-synaptotagmin), and of some crucially important enzymes: adenilyl cyclase, various protein kinases (ά, ε, C, MAP, Akt), mitochondrial respiratory chain enzyme complexes, histone deacetylase and acetyltransferase, GSK-3. Thus, in the long run “mood-stabilising agents” exert blockade of excitotoxic/apoptotic pathways, phosphorilation of microtubular proteins, and regulation of the expression of genes implicated in processes involved in neuroplasticity, neuroprotection, even neurogenesis, and hamper the long-term neuronal (and by extension, mental) deterioration. Lithium displays the broadest spectrum of such actions and provides, by far, the best control over the chronic protean symptoms of BAD.

Apoptosis recruits two-pore domain potassium channels used for homeostatic volume regulation

2002 ◽  
Vol 282 (3) ◽  
pp. C588-C594 ◽  
Author(s):  
James R. Trimarchi ◽  
Lin Liu ◽  
Peter J. S. Smith ◽  
David L. Keefe
Keyword(s):  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Biophysical Properties ◽  
Cell Shrinkage ◽  
Potential Therapeutic Target ◽  
Pharmacological Agents ◽  
Transmembrane Voltage ◽  
Intracellular Messengers ◽  
Pore Domain ◽  
Early Phases

Cell shrinkage is an incipient hallmark of apoptosis and is accompanied by potassium release that decreases the concentration of intracellular potassium and regulates apoptotic progression. The plasma membrane K+channel recruited during apoptosis has not been characterized despite its importance as a potential therapeutic target. Here we provide evidence that two-pore domain K+ (K2P) channels underlie K+ efflux during apoptotic volume decreases (AVD) in mouse embryos. These K2P channels are inhibited by quinine but are not blocked by an array of pharmacological agents that antagonize other K+ channels. The K2P channels are uniquely suited to participate in the early phases of apoptosis because they are not modulated by common intracellular messengers such as calcium, ATP, and arachidonic acid, transmembrane voltage, or the cytoskeleton. A K+channel with similar biophysical properties coordinates regulatory volume decreases (RVD) triggered by changing osmotic conditions. We propose that K2P channels are the pathway by which K+ effluxes during AVD and RVD and that apoptosis co-opts mechanisms more routinely employed for homeostatic cell volume regulation.

scholarly journals Inflammation and Pharmacological Treatment in Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Snježana Kaštelan ◽  
Martina Tomić ◽  
Antonela Gverović Antunica ◽  
Jasminka Salopek Rabatić ◽  
Spomenka Ljubić
Keyword(s):  
Diabetic Retinopathy ◽  
Pharmacological Treatment ◽  
Randomized Clinical Trials ◽  
Developed Countries ◽  
Aqueous Fluid ◽  
Inflammatory Factors ◽  
Pharmacological Agents ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Pharmacologic Treatments

Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer.

Formation of releasable γ-aminobutyrate from putrescine by rat adrenal slices in vitro

1989 ◽  
Vol 123 (2) ◽  
pp. 227-232 ◽  
Author(s):  
B. B. Oon ◽  
P. R. Scraggs ◽  
B. Gillham
Keyword(s):  
Catalytic Activity ◽  
Adrenal Gland ◽  
Incubation Medium ◽  
Functional Significance ◽  
Response Curve ◽  
Diamine Oxidase ◽  
Adrenal Glands ◽  
Metabolic Transformation ◽  
Stimulation Of

ABSTRACT Rat adrenal gland slices, when incubated in vitro with [1,4-14C]putrescine, accumulate the radioactive diamine and convert it, in part, to a compound indistinguishable (in four separative systems) from [14C]γ-aminobutyrate (GABA). Adrenal glands taken from animals that had undergone adrenal enucleation 28 days previously, so that the cortex of the tissue had regenerated, likewise formed [14C]GABA from [1,4-14C]putrescine. Putrescine-derived GABA was released from adrenal slices in vitro by 48 mmol K+/l, the release being dependent upon the presence of Ca2+ in the incubation medium. ACTH(1–24) and 8-bromocyclic AMP both provoked a dose-related release of putrescine-derived GABA, although the dose–response curve for the latter differed somewhat from that for the release of corticosterone by this secretogogue. The enzyme believed to be responsible for the first step in the metabolic transformation of putrescine into GABA, diamine oxidase (DAO), is present in extracts of adrenal tissue and its catalytic activity underwent a transient increase followed by a fall below resting levels upon stimulation of adrenal slices with ACTH(1–24). The conclusion that this enzyme initiates the formation of GABA by this pathway is indicated by the observation that adrenal slices pretreated with the DAO inhibitor, aminoguanidine, released significantly less [1,4-14C]putrescine-derived GABA in response to 48 mmol K+/l than did control tissues. The functional significance of these findings remains to be established. Journal of Endocrinology (1989) 123, 227–232

scholarly journals Interpretation of C-Reactive Protein Concentrations in Critically Ill Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Christophe Lelubre ◽  
Sophie Anselin ◽  
Karim Zouaoui Boudjeltia ◽  
Patrick Biston ◽  
Michaël Piagnerelli
Keyword(s):  
Clinical Practice ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Process ◽  
Early Recognition ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Pathophysiological Role ◽  
Inflammatory Processes

Infection is often difficult to recognize in critically ill patients because of the marked coexisting inflammatory process. Lack of early recognition prevents timely resuscitation and effective antimicrobial therapy, resulting in increased morbidity and mortality. Measurement of a biomarker, such as C-reactive protein (CRP) concentration, in addition to history and physical signs, could facilitate diagnosis. Although frequently measured in clinical practice, few studies have reported on the pathophysiological role of this biomarker and its predictive value in critically ill patients. In this review, we discuss the pathophysiological role of CRP and its potential interpretation in the inflammatory processes observed in critically ill patients.

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