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Histamine, a biological amine, is considered as a principle mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. It stimulates different biological activities through differential expression of four types of histamine receptors (H1R, H2R, H3R and H4R) on secretion by effector cells (mast...
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... different mammalian tissues, the study of the distribu- tion of histamine H1-receptors (H1Rs) has been significantly helped by the development of specific radioligands for this subtype. In 1997, [3H]mepyramine a selective radioligand was developed ( Table 1) [62], and since then it has been used to identify H1-receptors in a wide variety of tissues such as gastrointestinal tract, central nervous system, air- ways and vascular smooth muscle cells, mammalian brain, hepatocytes, nerve cells, endothelial cells, chondrocytes, monocytes, neutrophils, dendritic cells, T and B lymphocytes (Table 2), the cardiovascular system and genitourinary sys- tem, endothelial cells and adrenal medulla in which H1- receptor mediates different biological properties of allergic responses such as typical immediate responses of allergic reaction type I like redness, itching and swelling ("triple re- sponse"). In many pathological processes of allergy, includ- ing allergenic rhinitis, atopic dermatitis, conjunctivitis, urti- caria, asthma, and anaphylaxis, H1-receptors are involved. ...
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... in the brain of guinea pig, whereas, it was used with lower success for localization in rat brain (Table 1) [78,81]. Slow dissociation of [3H]mepyramine from H1Rs has been shown at low temperature (i.e., 4°C) and this denotes that [3H]mepyramine can also be used for autoradiography (Ta- [84,85]. ...
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... study of H1R on human T lymphocytes has been characterized by use of [125I]iodobolpyramine [103] (see also Table 1) and is shown to increase (Ca 2+ )i [104]. It is being documented that H1R-deficient mice display both strong systemic T cell and efficient B cell responses to anti- gen [105]. ...
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... functional characterization of H1R has benefited from the use of many potent and specific antagonists (see Tables 1 and 3) [63,126]. H1-receptor antagonists are the oldest therapeutic tools of the modern medicine due to their sedative side effects, and the anti-allergic drugs which were developed initially, have now been abandoned. ...
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... structural studies done by photoaffinity binding prop- erties using [125I]iodoazidophenpyramine (Table 1) and subsequent sodium dodecyl sulfate polyacrylamide gel elec- trophoresis (SDS-PAGE) analysis demonstrated that the H1- receptor protein (molecular weight 56 kDa) is found under reducing conditions in the brain of rat, guinea pig, and mouse [79,118,129]. Similar studies have also been done by using photoaffinity ligand [3H] azidobenzamide in bovine adrenal medullar membranes and found labeled peptides in the size range 53 to 58 kDa [130]. ...
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... studies have also been done by using photoaffinity ligand [3H] azidobenzamide in bovine adrenal medullar membranes and found labeled peptides in the size range 53 to 58 kDa [130]. In guinea pig heart, the specifically labeled H1R with [125I]iodoazidophenpyramine was found to contain substantially higher molecular weight, while there was no obvious difference in the characteristics of the H1R in tissues ( Table 1) [131]. In 1991, H1R was cloned from the bovine adrenal medulla by expression clon- ing in the Xenopus oocyte system. ...
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... short 3 rd intra-cellular loop and the long C-terminal tail make a suitable feature of H2R subtype, and the rat N-terminal extracellular tail has N- linked glycosylation sites [164]. Similar to H1R, H2R is ex- pressed in different cell types ( 2-(Thiazol-2- yl)ethanamine Hill [89] designed a study to map the distribution of H2Rs by using radiolabeled H2R-antagonists, and achieved more affinity with [3H] titotidine (Table 1) for the H2R in guinea pig brain, lung parenchyma, and CHO-K1 cells trans- fected with the human H2-receptor cDNA [165][166][167], but it was not successful in the studies of rat brain [168]. The most successful H2R-radioligand is [125I]iodoaminopotenti-dine, which has high affinity (K D 50.3 nM) for the H2R in brain membranes (Table 1) [129,[169][170][171] and also in CHO-K1 cells expressing the cloned rat H2R [171]. ...
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... to H1R, H2R is ex- pressed in different cell types ( 2-(Thiazol-2- yl)ethanamine Hill [89] designed a study to map the distribution of H2Rs by using radiolabeled H2R-antagonists, and achieved more affinity with [3H] titotidine (Table 1) for the H2R in guinea pig brain, lung parenchyma, and CHO-K1 cells trans- fected with the human H2-receptor cDNA [165][166][167], but it was not successful in the studies of rat brain [168]. The most successful H2R-radioligand is [125I]iodoaminopotenti-dine, which has high affinity (K D 50.3 nM) for the H2R in brain membranes (Table 1) [129,[169][170][171] and also in CHO-K1 cells expressing the cloned rat H2R [171]. This compound has also been used for autoradiographic mapping of H2Rs in the brain of mammal [131,170]. ...
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... compound has also been used for autoradiographic mapping of H2Rs in the brain of mammal [131,170]. [125I]iodo- aminopotentidine is also the most successful H2R-radio- ligand (Table 1), which was used to map the distribution of H2Rs in human brain with highest densities in the basal gan- glia, hippocampus, amygdale, and cerebral cortex, and also lowest densities were identified in cerebellum and hypo- thalamus [170]. In guinea pig brain, a similar distribution has been observed [129]. ...
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... guinea pig brain, a similar distribution has been observed [129]. Irreversible labeling has also been suc- cessfully seen by [125I]iodoazidopotentidine (Table 1) [129,169]. H2R-stimulated cyclic AMP accumulation or adenylyl cyclase activity in Fig. (4) has been shown in various tissues including gastric cells, cardic tissue and brain [165,172,173] and gastric cells [174]. ...
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... intronless gene (DNA) sequences en- code 359 amino acids for canine, human, guinea pig or 358 amino acids for rat receptor protein which has the general properties of a G-protein-coupled receptor (GPCR) ( Table 2). The radioligand binding studies using [125I]iodoamino- potentidine were attempted to show the expression of rat and human H2R proteins in CHO cells and revealed the expected pharmacological specificity as shown in Table 1 [150,171]. Chromosomal mapping studies have demonstrated that the H2R gene was localized to human chromosome 5 [192]. ...
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... intact cellular sys- tems, most of the neuroleptics and antidepressants were ap- proximately 2 orders of magnitude weaker as antagonists of histamine-stimulated cAMP accumulation [203,205]. One highly potential explanation of these variations resides within the buffer systems used for the cell-free adenylyl cy- clase assays, and some differences in potency of some anti- depressants and neuroleptics have been demonstrated when membrane binding of H2Rs has been evaluated using [125I]iodoaminopotentidine (Table 1). However, the varia- tions observed in the Ki values deduced from studies of ligand binding in different buffers are not as large as the variations in K B values obtained from functional studies. ...
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... the periphery, H3R can be found with low density in gastrointestinal, bronchial and cardiovascular system [221]. The high apparent affinity of R-()- methylhistamine for the H3R has enabled the use of this compound as a radiolabeled probe ( Table 1) [222]. In rat cerebral cortical membranes, this compound (R-()- methylhistamine) has been used to identify a single binding site, and which in phosphate buffer has the important phar- macological characteristics of the H3R [222,223]. ...
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... binding has also been characterized using [3H]R-()-methylhistamine in guinea pig lung [222], guinea pig cerebral cortical mem- branes [226], guinea pig intestine and guinea pig pancreas [227]. N-methylhistamine as a radiolabeled probe had proved successful for the H3R ( Table 1). The relative agonist activity of N-methylhistamine (with respect to histamine) was significantly similar for all three histamine receptor (HRs) subtypes, but the binding affinity of histamine and N-methylhistamine for the H3R was several orders of mag- nitude higher than for either H1-or H2-receptors [23,131]. ...
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... is important to note that the inhibitory effect of sodium (Na 2+ ) ions on agonist binding means higher B max values that were usually obtained in sodium-free Tris buffers compared with the Na/K phosphate buffers [228]. The multiple histamine H3R subtypes exist in rat brain (termed H 3A and H 3B ) on the basis of [ 3 H]N - methylhistamine binding in rat cerebral cortical membranes in 50 mM Tris buffer ( Table 1) [230]. Based on these condi- tions, the selective histamine H3-antagonist thioperamide can discriminate two affinity-binding states [230]. ...
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... if thioperamide preferentially binds to uncoupled receptors, then this compound should exhibit negative efficacy in func- tional assays. Radiolabeled H3R antagonists [125I]iodo- phenpropit, has been used to label histamine H3Rs in rat brain membranes (Table 1) [231]. The inhibition curves for iodophenpropit and thioperamide were consistent with inter- action with a single binding site, but H3R agonists were found to be able to discriminate both high-[4 nM for R-()- methylhistamine] and low-[0.2 ...
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... shares 37-43% homology (58% in transmembrane regions) with the H3-receptor and a similar genomic structure. The H4R gene spans more than 21 kbp and contains three exons, separated by two large introns (>7 kb) ( Table 1) with large interspecies variations from 65-72% homology in sequences. Analysis of the 5 flanking region did not reveal the canoni- cal TATA or CAAT-boxes. ...
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... has been observed that H3R-agonist R- -methyl histamine acts on H4R with several hundred times less potency. Similar effect has been seen with thioperamide, the classical H3R antagonist which also behave like a H4R antagonist (Table 1), though with a much lower affinity and clobenpropit, also a H3R antagonist, which exerts agonistic activity on H4R [Table 1; 21, 273, 274, 283-286]. ...
Similar publications
The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapin...
Citations
... Effects driven by histamine may interfere with cellular survival. Activation of H 1 and H 2 receptors in CNS neurons causes the release of calcium ions (Ca 2+ ) from the endoplasmic reticulum followed by the production of arachidonic acid, nitric oxide (NO), and reactive oxygen species (ROS) (Molina-Hernández and Velasco 2008;Shahid et al. 2009;Panula et al. 2015). The production of ROS is controlled by defense systems which can involve superoxide dismutase, catalase (CAT), glutathione peroxidase, and glutathione reductase (Halliwell. ...
Histamine is a biogenic amine implicated in various biological and pathological processes. Convenient cellular models are needed to screen and develop new antihistamine agents. This report aimed to characterize the response of neurons differentiated from mouse P19 embryonal carcinoma cells to histamine treatment, and to investigate the modulation of this response by antihistamine drugs, vegetal diamine oxidase, and catalase. The exposure of P19 neurons to histamine reduced cell viability to 65% maximally. This effect involves specific histamine receptors, since it was prevented by treatment with desloratadine and cimetidine, respectively, H1 and H2 antagonists, but not by the H3 antagonist ciproxifan. RT-PCR analysis showed that P19 neurons express H1 and H2 receptors, and the H3 receptor, although it seemed not involved in the histamine effect on these cells. The H4 receptor was not expressed. H1 and H2 antagonists as well as vegetal diamine oxidase diminished the intracellular Ca²⁺ mobilization triggered by histamine. The treatment with vegetal diamine oxidase or catalase protected against mortality and a significant reduction of H2O2 level, generated from the cells under the histamine action, was found upon treatments with desloratadine, cimetidine, vegetal diamine oxidase, or catalase. Overall, the results indicate the expression of functional histamine receptors and open the possibility of using P19 neurons as model system to study the roles of histamine and related drugs in neuronal pathogenesis. This model is less expensive to operate and can be easily implemented by current laboratories of analysis and by Contract Research Organizations.
... 1,4,5 Newer treatments are being developed, but antihistamines remain the cornerstone of the therapeutic approach. [6][7][8] Second-generation H 1 -antihistamines, compared with their first-generation drugs, have demonstrated improved peripheral H 1 -receptor selectivity, decreased lipophilicity and additional antiallergic properties apart from being histamine inverse agonists. 9 The mast cell is the major effector cell in most forms of urticaria. ...
Background
Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H 1 receptor antagonist used in the treatment of urticaria.
Aim
To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria.
Methods
The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student’s t -test was done for quantitative variables.
Results
There was a significant decrease in mean urticaria activity score ( P < 0.001), chronic urticaria quality of life ( P < 0.001) and clinical global improvement ( P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week ( P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56)
Limitations
Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned.
Conclusion
This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.
... and Polyamines Histamine is a major neurotransmitter and central modulator of immune responses and represents thus a central signal molecule in humans (Shahid et al. 2009). A number of bacteria were also found to synthesize and secrete histamine (Landete et al. 2008). ...
Based on genome analyses, it has been estimated that more than half of the bacteria have made an important investment into motility since they possess genes encoding the flagellar motor, the flagellum, chemosensory pathways and chemoreceptors. The metabolic burden associated with gene maintenance, protein synthesis and operating these systems is very important. A central question is thus to establish the physiological benefits that compensate such an important investment. In this chapter, we illustrate that benefits are multiple and diverse, including access to nutrients and preferred niches, biofilm formation and bacterial dispersal. There is also evidence that the complete range of advantages still remains to be defined. In these research efforts, Pseudomonas aeruginosa (PA) has played a central role and is among the central model species. Research conducted on PA had a significant impact in the field and has motivated many experiments in the study of other model bacterial species.
... AngaD7L3 binds serotonin (K D = 2 × 10 1 ± 4 × 10 0 nM), a novel activity for a member of the anopheline D7 long-form family. Given the K D values between ligands and their receptors are in the nM range (19), AngaD7Ls would be a good competitor for scavenging these molecules at the bite site. ...
To successfully feed on blood, hematophagous arthropods must combat the host's natural hemostatic and inflammatory responses. Salivary proteins of blood-feeding insects such as mosquitoes contain compounds that inhibit these common host defenses against blood loss, including vasoconstriction, platelet aggregation, blood clotting, pain, and itching. The D7 proteins are some of the most abundantly expressed proteins in female mosquito salivary glands and have been implicated in inhibiting host hemostatic and inflammatory responses. Anopheles gambiae, the primary vector of malaria, expresses three D7 long-form and five D7 short-form proteins. Previous studies have characterized the AngaD7 short-forms, but the D7 long-form proteins have not yet been characterized in detail. Here, we characterized the An. gambiae D7 long-forms by first determining their binding kinetics to hemostatic agonists such as leukotrienes and serotonin, which are potent activators of vasoconstriction, edema formation, and postcapillary venule leakage, followed by ex vivo functional assays. We found that AngaD7L1 binds leukotriene C4 and thromboxane A2 analog U-46619; AngaD7L2 weakly binds leukotrienes B4 and D4; and AngaD7L3 binds serotonin. Subsequent functional assays confirmed AngaD7L1 inhibits U-46619-induced platelet aggregation and vasoconstriction, and AngaD7L3 inhibits serotonin-induced platelet aggregation and vasoconstriction. It is therefore possible AngaD7L proteins counteract host hemostasis by scavenging these mediators. Finally, we demonstrate that AngaD7L2 had a dose-dependent anticoagulant effect via the intrinsic coagulation pathway by interacting with factors XII, XIIa, and XI. The uncovering of these interactions in the present study will be essential for comprehensive understanding of the vector-host biochemical interface.
... It is not a drug but significant due to its physiological and pathophysiological activities [20]. Consequently, drugs that prevent its release or block its receptors have therapeutic value (Fig. 9). ...
... Histamine and its biological actions [20] Fig. 8 Precursor for histamine [20] ...
... Histamine and its biological actions [20] Fig. 8 Precursor for histamine [20] ...
Imidazole and its derivatives are one of the most important and widely used heterocycles in medicinal chemistry, natural products, and synthetic chemicals. Because of the imidazole ring's unique structural features, imidazole derivatives may easily attach to a wide range of enzymes and receptors via a number of weak interactions, demonstrating a wide range of biological and pharmacological effects. Several imidazole derivatives have been widely used in the clinic to treat a wide range of illnesses, suggesting their enormous potential for further research. In the realm of medicinal chemistry, this chapter presents a comprehensive summary of current findings in imidazole derivatives as anti-inflammatory, anticancer, antiviral, antibacterial, and other therapeutic agents.
... Histamine, mediated by the activation of its four receptors (H1R-H4R), exhibits extensive effects related to visceral fat mass. It is known to function as a human neurotransmitter, a modulator of inflammatory and immune responses, and a key mediator of several allergic pathways and autoimmune pathogeneses (Mohammad et al., 2009). Innate and adaptive immune cells throughout the body can produce histamine by decarboxylation of the amino acid L-histidine by the enzyme histidine decarboxylase (HDC) (Jutel et al., 2009). ...
Twenty-Five Wei’er Tea Pills (TFP), a traditional Tibetan medicine, has shown to have a promising therapeutic effect in patients with Rheumatoid arthritis (RA), as well as being safe. Nonetheless, there have been limited pharmacological studies that have explored this therapeutic option. As gut microbiota has been proven to have a critical role in the pathogenesis of RA, this study aims to explore and reveal relevant ways by which TFP interacts with the chemical crosstalk between the gut microbiome and its host. 16S rRNA sequencing, combined with un-targeted metabolomics, were conducted on collagen-induced arthritis (CIA) rats. CIA model rats treated with TFP showed significant improvement in weight gain, pathological phenomena in joints, as well as decreased serum levels of TNF-α, IL-6 and increased level of IL-4 and IL-10. Significant dysfunction in the gut microbiome and alteration in serum metabolites were observed in CIA model rats, which were restored by TFP treatment. Coherence analysis indicated that TFP modulated the pathways of histidine metabolism, phenylalanine metabolism, alanine, aspartate, glutamate metabolism, amino sugar and nucleotide sugar metabolism owing to the abundances of Lactobacillus , Bacteroides , Prevotellaceae _UCG-001 and Christensenellaceae _R-7_group in the gut microflora. The corresponding metabolites involved L-histidine, histamine, phenylethylamine, asparagine, L-aspartic acid, D-fructose 1-phosphate, D-Mannose 6-phosphate, D-Glucose 6-phosphate, and Glucose 1-phosphate. In conclusion, this study reveals the ameliorative effects of TFP on RA through the chemical crosstalk that exists between the gut microbiota and its host, and also further enriches our understandings of the pathogenesis of RA.
... We used two different chemical stimuli in this model-histamine and IL-1β. Histamine stimulates endothelial cells quickly and induces the fusion of Weibel-Palade bodies with the endothelial cell membrane where its cargo, including vWF and P-selectin, are released 192 .Stimulation of the histamine H1 receptor on the endothelial cell surface leads to additional downstream changes in the endothelium, including cell contraction, synthesis of prostacyclin and platelet-activating factor, and nitric oxide release193 . IL-1β activates NF-κB, a transcription factor that plays a major role in mediating inflammation, in endothelial cells via the 'canonical' pathway192 . ...
Platelets play a major role in vivo in preventing bleeding, hemostasis, and contributing to uncontrolled clotting, thrombosis. Platelets are impacted in health and disease by the other cells they encounter in blood flow, including red blood cells (RBCs), white blood cells (WBCs), and the endothelial cell monolayer lining blood vessel walls. Despite this importance, the effect other cell types have on platelets in disease has yet to be fully explored, in part due to a lack of proper models to study human platelet behavior. In this thesis, we develop new, tunable in vitro methods to study platelet behavior that can be altered depending on disease conditions. We examined platelet adhesion to a confluent endothelial cell monolayer cultured on crosslinked extracellular matrix proteins, which were exposed via manual damage. We attached the damaged endothelial cells to a parallel plate flow chamber and monitored human platelet behavior and adhesion over a wide variety of blood flow conditions. This model was validated using a known anti-platelet compound and we identified two additional novel compounds that significantly reduced platelet adhesion when administered either to blood or to the endothelial cells themselves. Many diseases, including acute lung injury, venous and arterial thrombosis, and sepsis, fall under the umbrella of ‘thromboinflammation,’ when blood clots occur in combination with an overzealous immune cell response. A hallmark of these diseases is the presence of leukocyte-platelet aggregates at the site of inflammation. To capture this phenomenon, we included inflammation of endothelial cells in our flow model to facilitate the adhesion of leukocyte-platelet aggregates. We then utilized model polymeric drug carriers to reduce platelet adhesion to the inflamed endothelium by interfering with platelet-bound leukocytes. Specifically, platelet adhesion in this model decreased by approximately two-fold after 2 µm polystyrene particles were introduced into the system. We verified that this impact of particles is translatable in vivo using a mouse model of systemic inflammation; 2 µm particles significantly reduced platelet adhesion to the mouse mesentery by up to 62% in comparison to non-particle controls. These findings represent a potential new particle-based therapeutic to reduce platelet accumulation in thromboinflammatory diseases by diverting platelet-leukocyte aggregates away from areas of inflammation. Patients with sickle cell disease (SCD) have RBCs that are more stiff than non-SCD controls; we explored the impact that these stiff RBCs have on platelet behavior in blood flow in vitro using SCD patient whole blood samples and a model system where healthy RBCs are artificially stiffened to mimic SCD. The magnitude of SCD platelet adhesion varied greatly depending on patient treatment regimen, though untreated patients had the highest platelet adhesion in comparison to non-SCD controls. Our artificial system allowed us to examine the impact of stiff RBCs on platelet adhesion in a controlled environment, providing knowledge that can help inform how to provide chronic transfusions of RBCs to SCD patients to best reduce excessive platelet adhesion and clotting. We also determined that carbon monoxide releasing molecules (CORMs) reduce excessive platelet adhesion for a subset of patients, a promising new potential therapeutic for SCD. Overall, this work represents new methods to study platelet behavior under different disease conditions as well as novel potential therapeutics to modulate platelet adhesion in thromboinflammation and SCD.
... Histamine, known as the inflammatory mediator in allergy, [28] was used in the biochemical reaction experiments of the blood vessel model. The barrier function of TJs of ECs is known to be broken by histamine reaction through the contraction of ECs. ...
Since the biochemical reaction of blood vessels plays an essential role in immune response or various diseases, in vitro vascular models have high demand from medical fields. However, vascular models often tend to be difficult to mimic the biomedical reaction faithfully because of the lack of implementation of the tissue deformation. Here, an inflammatory mediator‐induced deformation reaction of a blood vessel on a flexibly deformable collagen hydrogel tube device is reproduced. A self‐standing collagen tube enables the tissue to deform flexibly in biochemical reaction and achieves contraction both at tissue and cell level. The contraction of tissue relieves the stress between cells under reaction to maintain cellular junctions even tight junctions are broken. Also, the drug perfusion test with antihistamine chemical is easily performed due to the connector part and properly inhibits the inflammatory reaction. Moreover, the traction force on endothelial cells is analyzed as about 0.9 µN on two types of scaffolds with different stiffness. It is believed that the potential of the flexible tissue model to reproduce biochemical reactions can contribute to the fabrication of vascular tissue models mimicking in vivo in high similarity as a platform for biomedical researches and pharmacokinetic testing.
... Histamine concentration is greatest within mast cells, but other types of cells, such as platelets, leukocytes, and enterochromaffin cells, can also synthesize and release histamine. [7][8][9][10] Once released, histamine mediates several physiologic responses, including type I hypersensitivity reactions, gastric acid production, smooth muscle motility, inflammation mediation, and vascular permeability. 7,8 Once synthesized, histamine has a short half-life; therefore, N-methylhistamine (NMH), a stable histamine metabolite, is commonly used to assess systemic histamine concentrations. ...
... [7][8][9][10] Once released, histamine mediates several physiologic responses, including type I hypersensitivity reactions, gastric acid production, smooth muscle motility, inflammation mediation, and vascular permeability. 7,8 Once synthesized, histamine has a short half-life; therefore, N-methylhistamine (NMH), a stable histamine metabolite, is commonly used to assess systemic histamine concentrations. 11,12 The histamine concentration within stored human blood products increases over time, especially OBJECTIVE To determine the effects of leukoreduction on N-methylhistamine (NMH; a stable histamine metabolite) concentration in units of canine whole blood during storage and incubation at room temperature (approx 22 °C) to simulate temperature conditions during transfusion. ...
Objective:
To determine the effects of leukoreduction on N-methylhistamine (NMH; a stable histamine metabolite) concentration in units of canine whole blood during storage and incubation at room temperature (approx 22 °C) to simulate temperature conditions during transfusion.
Animals:
8 healthy adult Walker Hounds.
Procedures:
A standard unit of blood (450 mL) was obtained from each dog twice, with at least 28 days between donations. Blood units collected from 4 dogs during the first donation underwent leukoreduction, whereas the blood units collected from the other 4 dogs did not undergo leukoreduction, prior to storage at 4 °C. The alternate treatment was applied to blood units collected during the second donation. A sample from each unit was obtained for determination of plasma NMH concentration the day of donation (before and after leukoreduction when applicable) and before and after incubation at room temperature for 5 hours on days 14 and 28 of storage.
Results:
Units that underwent leukoreduction had substantially lower leukocyte and platelet counts than nonleukoreduced units. Plasma NMH concentration increased immediately after leukoreduction but did not change significantly during the subsequent 28 days of storage, nor did it differ between units that did and did not undergo leukoreduction.
Conclusions and clinical relevance:
Leukoreduction and simulated transfusion temperature did not affect the histamine load in units of canine whole blood during the first 28 days of storage. Further research is necessary to determine whether histamine contributes to the development and severity of blood transfusion reactions in dogs.
... [37][38][39] The H 3 receptor is a Gαi/0-coupled protein receptor, and its activation leads to inhibition of cAMP formation, accumulation of Ca 2+ , and stimulation of the MAPK pathway. 40,41 Although primarily described in the CNS, it is additionally found in other tissues including some immune cells. 5,42 The H 3 receptor acts as an autoreceptor and heteroreceptor, regulating the release of histamine from histaminergic neurons and of various other neurotransmitters. ...
... 8,[49][50][51][52] Activation of H 4 receptor leads to the inhibition of AC and downstream cAMP-responsive elements as well as the activation of MAPK and PLC with Ca 2+ mobilization. 25,34,35,41 Numerous in vivo studies have demonstrated that the H 4 receptor plays an important role in inflammation and pruritus. Clinical trials are already in the way to assess the effectiveness of various H 4 receptor antagonists. ...
Cancer is the second leading cause of death globally and its incidence and mortality are rapidly increasing worldwide. The dynamic interaction of immune cells and tumor cells determines the clinical outcome of cancer. Immunotherapy comes to the forefront of cancer treatments, resulting in impressive and durable responses but only in a fraction of patients. Thus, understanding the characteristics and profiles of immune cells in the tumor microenvironment (TME) is a necessary step to move forward in the design of new immunomodulatory strategies that can boost the immune system to fight cancer. Histamine produces a complex and fine-tuned regulation of the phenotype and functions of the different immune cells, participating in multiple regulatory responses of the innate and adaptive immunity. Considering the important actions of histamine-producing immune cells in the TME, in this review we first address the most important immunomodulatory roles of histamine and histamine receptors in the context of cancer development and progression. In addition, this review highlights the current progress and foundational developments in the field of cancer immunotherapy in combination with histamine and pharmacological compounds targeting histamine receptors.
