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Cetirizine is an antihistamine commonly used to treat allergic rhinitis and other allergic conditions. Cetirizine is often prescribed to breastfeeding mothers although there is limited information on infant exposure via breast milk. The aim of this study was to develop a popPK model based on data from a lactation study to predict cetirizine breast milk concentrations and estimate the relative infant dose (RID) in a breastfed infant. A popPK model was developed in NONMEM on data from a human lactation study including 35 women using cetirizine or levocetirizine while breastfeeding. Serial samples of breast milk were collected (n = 205) and the cetirizine concentrations quantified using a validated LC–MS/MS method. A one‐compartment model of cetirizine in breast milk was developed and employed to calculate the relative infant dose (RID). Covariates related to the maternal characteristics and breastfeeding patterns were evaluated in the model; only milk sampling pumping duration was found to be a significant covariate, with an increasing pumping duration leading to an increased apparent milk volume of distribution (Vm). The mean RID was 1.99% with the highest RID being 3.36% at Cmax. PopPK modelling could be used to estimate infant exposure to cetirizine via breast milk. The low predicted exposure in infants supports that cetirizine is compatible with breastfeeding. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value. Methods: We included patients with evidence of ACLD, defined by portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mmHg) and/or a liver stiffness measurement by transient elastography ≥10 kPa, who underwent HVPG measurement between 2017 and 2020. Acute‐on‐chronic liver failure (ACLF) and/or liver‐related death were defined as composite endpoint. Results: Of 251 patients, 82.5% had clinically significant portal hypertension (median HVPG: 17 mmHg [interquartile range (IQR) 12–21]) and 135 patients (53.8%) were decompensated at baseline. Median plasma histamine was 8.5 nmol/L (IQR: 6.4–11.5), 37.1% of patients showed elevated values (>9.9 nmol/L). Histamine levels did not differ significantly across Child‐Turcotte‐Pugh (CTP) stages nor strata of model for end‐stage liver disease (MELD) or HVPG. Histamine levels correlated with markers of circulatory dysfunction (i.e. sodium, renin and aldosterone). During a median follow‐up of 29.2 months, 68 patients developed ACLF or liver‐related death. In univariate as well as in multivariate analysis (adjusting for age, sex, HVPG as well as either MELD, clinical stage, and serum albumin or CTP and serum sodium), elevated histamine levels remained associated with the composite endpoint. CTP‐based multivariate model adjusted sub‐distribution hazard ratio (asHR): 1.010 (95% CI: 1.004–1.021), p <.001; MELD‐based multivariate model asHR: 1.030 (95% CI: 1.017–1.040), p <.001. Conclusion: High levels of histamine were linked to circulatory dysfunction in ACLD patients and independently associated with increased risks of ACLF or liver‐related death. Further mechanistic studies on the link between histamine signalling and development of hyperdynamic circulation and ACLF are warranted. [ABSTRACT FROM AUTHOR]

A molecularly imprinted polymer-based dispersive micro-solid-phase extraction method has been developed for the efficient extraction and preconcentration of histamine from tuna fish samples prior to its determination by gas chromatography–flame ionization detector. In this approach, a molecularly imprinted polymer was prepared by chemical oxidation of pyrrole using iron (III) chloride, and then, it was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy and used in the extraction procedure. The method was validated using the International Council Research Protocol, and the results showed low limits of detection (0.06 mg kg−1) and quantification (0.21 mg kg−1), good precision (relative standard deviation = 3.2%), linearity (r2 ≥ 0.9969) and acceptable extraction recovery (98%). The method was successfully done on various tuna fish samples, and histamine was determined in them. [ABSTRACT FROM AUTHOR]

Background: Innovative treatments are being examined to develop more effective and innocuous protective medications for allergic conditions. In recent times, helminth-based immunotherapy is gaining attention as a potential therapeutic approach that could establish a pathway for controlling anaphylaxis. To the extent of our knowledge, there are no previous studies that examine the protective effect of both Schistosoma mansoni (S. mansoni) and its soluble egg antigen (SEA) together against anaphylaxis. Therefore, the purpose of the current study was to examine and compare the impact of SEA immunization and/or S. mansoni infection on Ovalbumin (OVA)-induced systemic anaphylaxes in mice model. Results: The outcome results revealed that S. mansoni infection and SEA immunization were able to improve body weight, reduce the mortality rate, increase plasma IgE and IgG4 levels and decrease histamine levels in broncho-alveolar lavage fluid (BALF). Additionally, they elevated interleukin-(IL)-4, IL-10, interferon-gamma (IFN-γ) and transforming growth factor-beta (ΤGF-β) levels in BALF. They also restored the stabilization of peritoneal mast cells (MCs) membrane in inverted light microscopy results accompanied by amelioration of the lung and liver histology. Conclusions: The present study provided indication for the prophylactic effects of S. mansoni infection and SEA immunization against OVA-induced systemic anaphylaxes in mice model. Also, it focuses on the possible therapeutic mechanisms of helminth-derived products administration that might be related to upregulation of immune regulatory mechanisms. As a result, S. mansoni-derived products may be used as preventative supplemented treatments to inhibit the development of anaphylaxis which provides us with a new vision for developing pioneering therapy. [ABSTRACT FROM AUTHOR]

Monoamine neurotransmitters generated by de novo synthesis are rapidly transported and stored into synaptic vesicles at axon terminals. This transport is essential both for sustaining synaptic transmission and for limiting the toxic effects of monoamines. Here, synthesis of the monoamine histamine by histidine decarboxylase (HDC) and subsequent loading of histamine into synaptic vesicles are shown to be physically and functionally coupled within Drosophila photoreceptor terminals. This process requires HDC anchoring to synaptic vesicles via interactions with N-ethylmaleimide-sensitive fusion protein 1 (NSF1). Disassociating HDC from synaptic vesicles disrupts visual synaptic transmission and causes somatic accumulation of histamine, which leads to retinal degeneration. We further identified a proteasome degradation system mediated by the E3 ubiquitin ligase, purity of essence (POE), which clears mislocalized HDC from the soma, thus eliminating the cytotoxic effects of histamine. Taken together, our results reveal a dual mechanism for translocation and degradation of HDC that ensures restriction of histamine synthesis to axonal terminals and at the same time rapid loading into synaptic vesicles. This is crucial for sustaining neurotransmission and protecting against cytotoxic monoamines. Synopsis: Neurotransmitters are key for synaptic transmission at axon terminals, but their transport modalities remain debated. This study demonstrates that coupling of histamine synthesis with its loading into synaptic vesicles by anchoring histidine decarboxylase (HDC) to synaptic vesicles is critical to maintaining neurotransmission and preventing cytotoxic side effects. Coupling histamine synthesis with synaptic vesicle loading is critical for neurotransmitter homeostasis and synaptic transmission. HDC is co-transported with synaptic vesicles to axonal terminals through binding with vesicle-fusing ATPase NSF1. HDC remaining in soma is degraded by the E3 ubiquitin ligase POE via the proteasome. Aberrant accumulation of histamine in the soma is cytotoxic and causes retinal degeneration. Anchoring of histidine decarboxylase to synaptic vesicles is critical to maintaining neurotransmission and preventing cytotoxic side effects. [ABSTRACT FROM AUTHOR]

Background Objective Animals Materials and Methods Results Conclusions and Clinical Relevance Intradermal allergen testing (IDAT) is commonly used to formulate allergen‐specific immunotherapy, a pillar treatment for canine atopic dermatitis. Many sedatives have shown histaminergic or anti‐histaminergic effects and thus been deemed unsuitable for IDAT.The goal of this study was to determine whether, in healthy dogs, dexmedetomidine (Dexdomitor) or a 1:20 combination of medetomidine and vatinoxan (Zenalpha) will affect intradermal reactions compared to unsedated dogs.Ten privately owned healthy dogs were enrolled in this equivalence study.Wheal formation was subjectively and objectively assessed in conscious then sedated dogs. Dogs were randomly sedated with either Dexdomitor (dexmedetomidine [0.5 mg/m2]) or Zenalpha (medetomidine [1 mg/m2/vatinoxan] 20 mg/m2) intramuscularly. Once sedated, five 10‐fold histamine (100–0.01 μg/mL) and compound 48/80 (200–0.02 μg/mL) dilutions were intradermally injected into the lateral thorax. The study was repeated on the opposite side with the alternative sedation 1 week later. Quality of sedation, cardiorespiratory function and rectal temperature were recorded every 5 min.There was no difference in the median values of the reactions with either sedative when compared to unsedated dogs. Dexdomitor and Zenalpha achieved an equivalence in both subjective and objective scoring systems for all concentrations tested. A faster median time to sedation (10 vs. 18 min, p = 0.013) was seen with Zenalpha compared to Dexdomitor. Although both sedatives depressed the cardiovascular function, such parameters were less affected by Zenalpha than by Dexdomitor (p ≤ 0.001).Owing to the lack of effects on wheal formation, both sedatives are appropriate for sedating dogs undergoing IDAT. Although, such results should be validated in allergic dogs. Zenalpha may induce more rapid and reliable sedation than Dexdomitor. [ABSTRACT FROM AUTHOR]

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multicenter collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of the transitional tele-rehabilitation programme on quality of life of adult burn survivors. Design: A prospective, single centre, randomised controlled trial and reported according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Participants: Adult burn survivors aged ≥18 years with burn size ≥10% total body surface area irrespective of the depth was considered eligible to participate. Intervention: The intervention was in two phases: pre-discharge and active follow-up phase (which occurred via WeChat). In both phases, comprehensive assessment and intervention guided by the Omaha System and evidenced-based protocols guided the care delivery over an 8-week period. Main measures: The outcome of interest was quality of life. Two outcome measures were used to assess the outcome of interest: Burn Specific Health Scale-Brief (BSHS-B) and the EQ-5D-5L tools. The outcome was assessed at three time points: T0 (baseline), T1 (immediate post-intervention) and T2 (4 weeks from T1). Results: In total, 60 adult burn survivors were randomly allocated to undergo the new programme. The transitional tele-rehabilitation programme elicited statistically significant improvement in simple abilities, affect, interpersonal relationship (T2) and overall quality life (T1 and T2) measured on the BSHS-B. Conclusion: Ongoing rehabilitative care is essential to support the recovery process of burn survivors considering that some quality-of-life subscales may improve faster than others. The study findings highlight the potential of employing a social media platform to improve post-burn quality of life outcomes. Trial registration: ClinicalTrials.govNCT04517721. Registered on 20 August 2020 [ABSTRACT FROM AUTHOR]

Odor information is modulated by centrifugal inputs from other brain regions to the olfactory bulb (OB). Neurons containing monoamines, such as serotonin, acetylcholine, and noradrenaline, are well known as centrifugal inputs; however, the role of histamine, which is also present in the OB, is not well understood. In this study, we examined the histaminergic neurons projecting from the hypothalamus to the OB. We used an antibody against histidine decarboxylase (HDC), a synthesizing enzyme of histamine, to identify histaminergic neurons and assess their localization within the OB and the ultrastructure of their fibers and synapses using multiple immunostaining laser microscopy, ultra‐high voltage electron microscopy (EM), and EM to confirm their relationships with other neurons. To further identify the origin nucleus of the histaminergic neurons projecting to the OB, we injected the retrograde tracer FluoroGold and analyzed the pathway to the OB anterogradely. HDC‐immunoreactive (‐ir) fibers were abundant in the olfactory nerve (ON) layer compared to other monoamines. HDC‐ir neurons received asymmetrical synapses from ONs and formed synapses containing pleomorphic vesicles with variable postsynaptic densities to non‐ON elements, thus forming serial synapses. We also confirmed that histaminergic neurons project from the rostral ventral tuberomammillary nucleus to the granule cell layer of the OB and, for the first time, successfully visualized their axons from the hypothalamus to the OB. These findings indicate that histamine may regulate odor discrimination in the OB, suggesting a regulatory relationship between hypothalamic function and olfaction. We thus elucidate morphological mechanisms with tuberomammillary nucleus–derived histaminergic neurons involved in olfactory information. [ABSTRACT FROM AUTHOR]

This study attempted to clarify the role of histamine H1 receptors in epilepsy by exploring the effects of agonists and inverse agonists on the rundown of the current induced by iterative applications of NMDA or GABA in primary neuronal culture. Mepyramine, a classical H1‐receptor antagonist/inverse agonist, increased the NMDA current by about 40% during the first minutes of recording. This effect was concentration‐dependent, maximal at 10 nM, and mimicked by triprolidine, another antagonist/inverse agonist. No endogenous histamine was detected in the cultures by a selective immunoassay; both compounds were acting as inverse agonists. Indicating a high constitutive activity of the H1 receptor in this system, histamine did not affect the NMDA rundown, including its settlement, but significantly reversed the effect of mepyramine. A similar pattern was obtained with 2,3 bromophenyl histamine, a selective H1‐receptor agonist. The initial increase induced by the two inverse agonists was followed by the same rundown as in controls. H1‐ and NMDA receptors are colocalized in most cultured neuronal cells. Mepyramine and histamine did not affect the GABA rundown. Our findings suggest an interaction between H1‐ and NMDA receptors. Inactivation of the H1‐receptor by its inverse agonists delays the settlement of the NMDA rundown, which may underlie their proconvulsant effect reported in clinics. Therefore, H1‐receptor constitutive activity and the effect of histamine revealed in its absence, tend to facilitate the initiation of the rundown, which is consistent with the anticonvulsant properties of histamine via activation of H1‐receptors reported in many studies. [ABSTRACT FROM AUTHOR]

Background: Antihistamines has always remained the mainstay drug treatment for Allergic Rhinitis (AR). Bilastine is a novel, non-sedative antihistamine with a super-selective H1 receptor antagonist property. Both bilastine and fexofenadine are second generation antihistamine drugs commonly used to manage AR and Chronic Urticaria (CU). Autologous Skin Serum Test (ASST) is a practical test for histamine release in CU. These tests have been studied in AR patients with limited data studies. Methods: 114 patients diagnosed with perennial AR were recruited and divided into two groups of 57 each. One group was started Bilastine 20 mg once a day and other group, fexofenadine 180 mg once a day. Total Nasal Symptom Score (TNSS) was calculated at presentation and two weeks of antihistamine therapy. ASST was hypothesized to be the test for AR and performed at the time of presentation and at two weeks follow-up. Intergroup and Intragroup assessment of TNSS, ASST and its variables were done using unpaired and paired t test respectively. Results: Patients showed reduction in symptoms of AR with both antihistamines. A significant improvement of sneezing and rhinorrhoea was seen in Fexofenadine group as compared to Bilastine group. TNSS showed statistically significant improvement in both the groups. ASST had statistically significant reduction in both the groups. Conclusions: Both Bilastine and fexofenadine were found to be effective in reduction of symptoms of allergic rhinitis. Bilastine was found to be more effective in overall as well as sneezing and rhinorrhoea noted two weeks after therapy. [ABSTRACT FROM AUTHOR]

Apart from their functions in the nervous system of animals, neurotransmitters operate as regulatory agents and signals in diverse kingdoms of life. Some neurotransmitters have recently been revealed to exert specific effects on microalgae, predominantly functioning as algal growth stimulators. This article presents new data on the effects of such neurotransmitters as serotonin, norepinephrine, dopamine, histamine, and acetylcholine on the fatty acid and pigment composition of the green microalga Scenedesmus quadricauda (Turp.) Breb. K-1149. It was established that acetylcholine and, to a lesser extent, histamine increased the total fatty acid content of S. quadricauda cells, whereas serotonin and dopamine decreased the fatty acid content. Acetylcholine, histamine, and norepinephrine elevated the percentage of polyunsaturated fatty acids; in contrast, serotonin and dopamine increased the share of saturated fatty acids. Acetylcholine and, to a lesser extent, norepinephrine increased the total chlorophyll content per gram of dry weight in S. quadricauda, while histamine decreased the chlorophyll content. Histamine also increased the chlorophyll a/chlorophyll b and carotenoid/chlorophyll ratios, which were decreased by dopamine. The data obtained are of biotechnological and ecological interest. The stimulation of fatty acid accumulation and the increase in the percentage of polyunsaturated species was caused by the neurotransmitters acetylcholine and histamine at low (1–10 μM) concentrations, which potentially enables facilitating the biotechnological production of health-promoting preparations for therapeutic and cosmetic purposes. However, other neurotransmitters (dopamine and serotonin) tested increased the relative content of saturated fatty acids; therefore, they apparently can be used to stimulate biofuel production, since saturated fatty acid-rich lipids are advantageous raw materials for biodiesel production. The impact of neurotransmitters on microalgal fatty acid composition and photosystem components may be considered in terms of ongoing chemical interaction between microalgae and other aquatic ecosystem components that are known to produce neurotransmitters. [ABSTRACT FROM AUTHOR]

Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers. We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance. Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores. Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance. [Display omitted] [ABSTRACT FROM AUTHOR]

Histamine is one of the most important and extensively studied biological molecules in the human body. It plays a constitutive role within almost every bodily system, but most notably within the stomach, where it regulates acid secretion, the central nervous system, where it acts as a neurotransmitter, the cardiovascular system, where it affects cardiac output and vascular permeability, and it has a well-established role in allergy and anaphylaxis. Histamine exerts its effects through four distinct receptor subtypes: H1, H2, H3 and H4. Predominantly, though not exclusively, these take the form of G-protein-coupled receptors. Clinically used antihistamines demonstrate inverse agonism to the histamine receptor and drugs are available with activity at H1, H2 and H3 receptors. H1 antihistamines are used in the treatment of allergy, and are classified as either first or second generation. First-generation antihistamines have significant sedative side effects. H2 antihistamines are predominantly used for the treatment of gastrooesophageal reflux and peptic ulcer disease; however, the most widely used of these, ranitidine, has been withdrawn from use due to (impurity related) safety concerns. H3 antihistamines have been explored for the treatment of neurological disease and to date the only licensed H3 antihistamine is used for the treatment of narcolepsy. Multiple uses have been suggested for H4 antihistamines, including immunomodulation, the treatment of asthma and even as an analgesic. However, no (commercially available) drug exists as of yet. [ABSTRACT FROM AUTHOR]

Introduction: Decongestants are commonly used drugs in clinical practice, and they can relieve nasal congestion caused by factors like influenza, rhinitis, and acute upper respiratory tract infection. Areas covered: In this article, we review the research outcomes about decongestants, which aim to provide beneficial information that can guide the clinical application of decongestants for clinicians. Expert opinion: Although the use of nasal decongestants is increasingly limited, caution rather than prohibition is now advocated. Scientific and accurate use of nasal decongestants can achieve satisfactory clinical effectiveness on nasal congestion, and it is not easy to produce adverse reactions. Patients with severe nasal congestion may use nasal decongestants solely or in combination with nasal corticosteroids or nasal antihistamines to exert a synergistic effect. The concentration, dose, frequency, and time of nasal decongestants determine whether drug-induced rhinitis will occur. Additionally, we recommend patients not to buy nasal sprays with unknown ingredients on the internet or in pharmacy, so as to avoid the risk of rhinitis medicamentosa. For patients with rhinitis medicamentosa, the use of nasal decongestants should be stopped immediately. However, more evidence is still needed to standardize the clinical use of nasal decongestants. [ABSTRACT FROM AUTHOR]

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Histamine (HA), a biogenic monoamine, exerts its pleiotropic effects through four H1R–H4R histamine receptors, which are also expressed in brain tissue. Together with the projections of HA-producing neurons located within the tuberomammillary nucleus (TMN), which innervate most areas of the brain, they constitute the histaminergic system. Thus, while remaining a mediator of the inflammatory reaction and immune system function, HA also acts as a neurotransmitter and a modulator of other neurotransmitter systems in the central nervous system (CNS). Although the detailed causes are still not fully understood, neuroinflammation seems to play a crucial role in the etiopathogenesis of both neurodevelopmental and neurodegenerative (neuropsychiatric) diseases, such as autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease (AD) and Parkinson's disease (PD). Given the increasing prevalence/diagnosis of these disorders and their socioeconomic impact, the need to develop effective forms of therapy has focused researchers' attention on the brain's histaminergic activity and other related signaling pathways. This review presents the current state of knowledge concerning the involvement of HA and the histaminergic system within the CNS in the development of neurodevelopmental and neurodegenerative disorders. To this end, the roles of HA in neurotransmission, neuroinflammation, and neurodevelopment are also discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Histamine may lead to low blood pressure, skin flushing and edema when it accumulates in large amounts in the body. Therefore, establishing sensitive methods for the detection of histamine in foods is extremely important to ensure food safety and human health.The MI‐Cu‐GMP NPs (2‐methylimidazole‐copper‐guanosine monophosphate nanozymes) with high laccase‐like activity were synthesized. Using the prepared molecular imprinted membrane as biomimetic antibody and MI‐Cu‐GMP NPs as marker, a sensitive direct competitive biomimetic enzyme‐linked immunoassay (BELISA) method for rapid detection of the histamine in foods was developed. Under optimal conditions, the limit of detection (LOD, IC15) and sensitivity (IC50) of the BELISA method for histamine was 0.05 mg L−1 and 1.22 mg L−1, respectively. The liquor samples spiked with histamine was detected by the BELISA method with satisfactory recoveries ranging from 90.00% to 116.00%. Further, the level of histamine in three samples (cooking wine, rice vinegar and soy sauce) was tested by the BELISA and high‐performance liquid chromatography (HPLC), with no significant difference found between the two methods.Given the advantages, the established BELISA method is expected to provide practical guidance for the monitoring of histamine in food and provides a foundation for the detection of other food hazards. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that inflammation is essential for embryo implantation and decidualization. Histamine, a proinflammatory factor that is present in almost all mammalian tissues, is synthesized through decarboxylating histidine by histidine decarboxylase (HDC). Although histamine is known to be essential for decidualization, the underlying mechanism remains undefined. In the present study, histamine had no obvious direct effects on in vitro decidualization in mice. However, the obvious differences in HDC protein levels between day 4 of pregnancy and day 4 of pseudopregnancy, as well as between delayed and activated implantation, suggested that the blastocyst may be involved in regulating HDC expression. Furthermore, blastocyst‐derived tumor necrosis factor α (TNFα) significantly increased HDC levels in the luminal epithelium. Histamine increased the levels of amphiregulin (AREG) and disintegrin and metalloproteinase domain‐containing protein 17 (ADAM17) proteins, which was abrogated by treatment with famotidine, a specific histamine type 2 receptor (H2R) inhibitor, or by TPAI‐1 (a specific inhibitor of ADAM17). Intraluminal injection of urocanic acid (HDC inhibitor) on day 4 of pregnancy significantly reduced the number of implantation sites on day 5 of pregnancy. TNFα‐stimulated increases in HDC, AREG and ADAM17 protein levels was abrogated by urocanic acid, a specific inhibitor of HDC. Additionally, AREG treatment significantly promoted in vitro decidualization. Collectively, our data suggests that blastocyst‐derived TNFα induces luminal epithelial histamine secretion, and histamine increases mouse decidualization through ADAM17‐mediated AREG release. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a persistent and recurrent inflammatory skin condition with a genetic basis. However, the fundamental reasons and mechanisms behind this phenomenon remain incompletely understood. While tea extracts are known to reduce histamine-induced skin allergies and inflammation, the specific mechanisms by which various types of Chinese tea provide their protective effects are still not fully elucidated. In this study, a model of skin itching induced by histamine is used to explore the functions and mechanisms of three types of tea extract (Keemun black tea (HC), Hangzhou green tea (LC), and Fujian white tea (BC)) in alleviating histamine-induced dermatitis. The components of three tea extracts are identified by UPLC-Q-TOF-MS, and we found that their main components are alkaloids, fatty acyls, flavonoids, organic acids, and phenols. The inhibitory effects of three types of tea extract on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in skin injury are investigated by MIC and flow cytometry. The three types of tea extract have an inhibitory effect on the growth of bacterial flora, with HC showing the best inhibitory activity. The effect of the three types of tea extract on histamine-induced dermatitis is also evaluated. Furthermore, itchy skin experiments, HE staining, toluidine blue staining, and immunohistochemical staining of mouse skin tissues were performed to determine the variations of scratching, epidermal thickness, mast cell number, IL-1β, and NGF content after the administration of the tea extracts. The three types of tea extracts all alleviate and inhibit skin itching, epidermal hyperplasia, and allergic dermatitis. BC effectively alleviates epidermal hyperplasia caused by skin allergies, and LC significantly downregulates NGF. HC reduces histamine-induced mast cell infiltration and downregulates IL-1β to alleviate skin itching. Consequently, tea emerges a potent natural product that can inhibit the growth of skin wound bacterial flora and exhibit skin repair effects on histamine-induced allergic dermatitis. [ABSTRACT FROM AUTHOR]

Summary: Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain‐sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS. [ABSTRACT FROM AUTHOR]

Sauerkraut, also known as pickled vegetables, is a traditional fermented food that is loved by many consumers for its unique flavor and rich nutritional value. This paper, written in the first person, explores the composition, taste, preparation process, and underlying chemical principles of sauerkraut. It also discusses the health effects and dietary recommendations for consuming sauerkraut. The aim is to promote traditional Chinese food culture and the ancient art of fermentation, enhance awareness of food safety and healthy eating, cultivate students' scientific literacy and practical skills, and foster a greater appreciation for chemistry. [ABSTRACT FROM AUTHOR]

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. Transient receptor potential vanilloid 1 (TRPV1) channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (P ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild-type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell-deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression, whereas control (no stress) mast cell-deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia (DRG) in WT mice exposed to RVS, but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction. NEW & NOTEWORTHY: Using pharmacological tools and transgenic mice in a repeated variate stress (RVS) model in female mice, we demonstrate that transient receptor potential vanilloid 1 (TRPV1) and mast cells contribute to the increased voiding frequency observed following RVS. TRPV1 and mast cells should continue to be considered as targets to improve bladder function in stress-induced bladder dysfunction. [ABSTRACT FROM AUTHOR]

We aimed to determine the in vitro and in vivo synergistic antiallergic effect of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC), and the antiallergic rhinitis (AR) properties of guaijaverin-rich Psidium guajava and EGCG-rich Camellia sinensis (ILS-F-2301). GEC showed synergistic inhibition of β-hexosaminidase by 4.20% and interleukin (IL)-4, -5, and -13 by 4.08%, 0.67%, and 4.71%, respectively, while increasing interferon (IFN)–γ by 12.43%, compared with EGCG only. In addition, 50 μg/mL of ILS-F-2301 inhibited β-hexosaminidase release, and inhibited IL-4, -5, and -13 by 61.54%, 58.79%, and 59.25%, respectively, while increasing IFN–γ (showing 133.14% activation). Moreover, 50 μg/mL of ILS-F-2301 suppressed p-STAT6 and GATA3, while p-STAT1 and T-bet increased, and 0.039 μg/mL of guaijaverin or 5.275 μg/mL of EGCG modulated T helper (Th)1- and Th2-related proteins. These data suggested that guaijaverin and EGCG in ILS-F-2301 was the main active compound involved in Th1/Th2 modulation. In the AR mouse model, the administration of ILS–F–2301 inhibited ovalbumin (OVA)-specific IgE, histamine in serum; it also inhibited IL-4 and -5 by 28.23% and 47.15%, respectively, while increasing IFN–γ (showing 37.11% activation), compared with OVA/Alu-treated mice. Taken together, our findings suggest that ILS–F–2301 is a functional food for alleviating anti-AR. [ABSTRACT FROM AUTHOR]

Background: Nausea and vomiting in pregnancy (NVP), or emesis gravidarum, is a frequent complication of early gestation with unclear causes, suspected to involve genetic, hormonal, and gastrointestinal factors. Our study investigated the association of human chorionic gonadotropin (hCG), histamine, diamine oxidase (DAO), thyroxine and pyridoxine and the severity of NVP symptoms and assessed the efficacy of a vitamin C-containing chewing gum as a potential NVP treatment. Methods: In this prospective, double-blinded, randomized, controlled trial, 111 participants were assigned to receive vitamin C-containing chewing gum, placebo gum, or no treatment at two follow-ups during early pregnancy. Maternal serum levels of hCG, histamine, DAO, thyroxine, and pyridoxine were measured and correlated with NVP severity using the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE-24) score. Results: Elevated maternal hCG levels were significantly associated with an increased PUQE-24 score (p < 0.001), while histamine levels showed no significant correlation (p = 0.68). Maternal DAO levels negatively correlated with NVP symptoms (p < 0.001) and elevated thyroxine (p < 0.001) and pyridoxine levels (p < 0.001) were associated with increased PUQE-24 scores. The vitamin C-containing chewing gum did not demonstrate efficacy in alleviating NVP symptoms compared to placebo gum or no treatment during the first (p = 0.62) and second follow-up visits (p = 0.87). Conclusions: Our study underscores the complexity of factors contributing to NVP, highlighting the significant roles of hCG and DAO, while histamine levels appear unrelated. Maternal thyroxine and pyridoxine levels also significantly correlate with NVP symptoms. Vitamin C-containing chewing gum was not effective as a treatment for NVP. Further large-scale studies are needed to better understand these interactions and develop targeted treatments in the future. [ABSTRACT FROM AUTHOR]

Aims: This study investigated histamine intake and its associations with clinical and biochemical findings in patients with Behçet syndrome. Methods: Patients with Behçet syndrome were prospectively enrolled using a crosssectional, multicenter, and online survey design. Sociodemographic parameters, including age, gender, smoking and alcohol intake, nutritional counseling history, anthropometric measurements, clinical characteristics, and biochemical results, were obtained using an online questionnaire. Dietary histamine intake was determined using a food frequency questionnaire. Results: The study included 66 patients (mean age: 37.5±11.3 years, women: 53%. Food consumption was reported to trigger oral aphthae in 81% of the individuals, and the most frequently reported triggers were eggplant (37.5%), tomatoes (37.5%), and citrus fruits (34.3%). There was a significant positive correlation between dietary histamine intake and white blood cell counts (r=0.650; p=0.050). There were no significant differences in the clinical characteristics, including oral aphthae, genital ulcers, uveitis, dermatologic lesions, gastrointestinal system involvement, joint involvement, and vascular involvement between patients with low and high dietary histamine intake. A positive correlation was found between dietary histamine intake and the frequency of attacks (r=0.324; p=0.008). Conclusions: This study showed that increased dietary histamine intake was associated with an increased frequency of attacks in patients with Behçet syndrome. Oral aphthae are associated with certain foods, such as eggplant, tomatoes, and citrus fruit. [ABSTRACT FROM AUTHOR]

Mast cell–derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell–derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown. We sought to identify the IL-4–induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions. RNA sequencing, Western blot, Ca2+ imaging, and barrier functional analyses were performed on the VE cell line (EA.hy926). Pharmacologic degraders (selective proteolysis-targeting chimera) and genetic (lentiviral short hairpin RNA) inhibitors were used to determine the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4–stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4–mediated amplification of histamine-induced hypovolemia. These studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis. [ABSTRACT FROM AUTHOR]

Bioactive amines in foods are associated with beneficial health effects, but some can also cause food poisoning and intolerance. This study aimed to investigate the occurrence and levels of nine bioactive amines in ten conventional and non-conventional fruits and vegetables (seriguela, marolo, custard apple, acerola, jabuticaba, starfruit, kale, ora-pro-nobis, almeirão-roxo, and serralha) using HPLC-FL. Putrescine was the prevalent amine in custard apple, acerola, and ora-pro-nobis; whereas spermidine was predominant in jabuticaba, starfruit, and kale; and tyramine in seriguela and marolo. Tryptamine was not detected in any sample. Histamine was only detected in ora-pro-nobis, and serotonin only in starfruit. Total amine contents ranged from 3.24 to 58.83 mg/kg, with the lowest levels in serralha and the highest in seriguela. The median contents of spermidine varied from 1.32 to 13.42 mg/kg, with the lowest levels in serralha and the highest in seriguela. The highest agmatine levels were found in acerola, starfruit and serralha. Based on the levels of amines, seriguela, marolo, custard apple, acerola, jabuticaba, and kale could be dietary sources of the polyamine spermidine; and starfruit a source of serotonin. However, individuals using monoamine-oxidase inhibitor drugs should limit the consumption of seriguela and marolo, due to the high tyramine levels, to avoid adverse effects. In a similar way, individuals with histamine intolerance should avoid the consumption of ora-pro-nobis. [ABSTRACT FROM AUTHOR]

Abstract Background Innovative treatments are being examined to develop more effective and innocuous protective medications for allergic conditions. In recent times, helminth-based immunotherapy is gaining attention as a potential therapeutic approach that could establish a pathway for controlling anaphylaxis. To the extent of our knowledge, there are no previous studies that examine the protective effect of both Schistosoma mansoni (S. mansoni) and its soluble egg antigen (SEA) together against anaphylaxis. Therefore, the purpose of the current study was to examine and compare the impact of SEA immunization and/or S. mansoni infection on Ovalbumin (OVA)-induced systemic anaphylaxes in mice model. Results The outcome results revealed that S. mansoni infection and SEA immunization were able to improve body weight, reduce the mortality rate, increase plasma IgE and IgG4 levels and decrease histamine levels in broncho-alveolar lavage fluid (BALF). Additionally, they elevated interleukin-(IL)-4, IL-10, interferon-gamma (IFN-γ) and transforming growth factor-beta (ΤGF-β) levels in BALF. They also restored the stabilization of peritoneal mast cells (MCs) membrane in inverted light microscopy results accompanied by amelioration of the lung and liver histology. Conclusions The present study provided indication for the prophylactic effects of S. mansoni infection and SEA immunization against OVA-induced systemic anaphylaxes in mice model. Also, it focuses on the possible therapeutic mechanisms of helminth-derived products administration that might be related to upregulation of immune regulatory mechanisms. As a result, S. mansoni-derived products may be used as preventative supplemented treatments to inhibit the development of anaphylaxis which provides us with a new vision for developing pioneering therapy.

Abstract Although the cellular prion protein (PrPC) has been evolutionarily conserved, the role of this protein remains elusive. Recent evidence indicates that PrPC may be involved in neuroinflammation and the immune response in the brain, and its expression may be modified via various mechanisms. Histamine is a proinflammatory mediator and neurotransmitter that stimulates numerous cells via interactions with histamine receptors 1-4 (HRH1-4). Since microglia are the innate immune cells of the central nervous system, we hypothesized that histamine-induced stimulation regulates the expression of PrPC in human-derived microglia. The human microglial clone 3 (HMC3) cell line was treated with histamine, and intracellular calcium levels were measured via a calcium flux assay. Cytokine production was monitored by enzyme-linked immunosorbent assay (ELISA). Western blotting and quantitative reverse transcription-polymerase chain reaction were used to determine protein and gene expression of HRH1-4. Flow cytometry and western blotting were used to measure PrPC expression levels. Fluorescence microscopy was used to examine Iba-1 and PrPC localization. HMC3 cells stimulated by histamine exhibited increased intracellular calcium levels and increased release of IL-6 and IL-8, while also modifying PrPC localization. HMC3 stimulated with histamine for 6 and 24 hours exhibited increased surface PrPC expression. Specifically, we found that stimulation of the HRH2 receptor was responsible for changes in surface PrPC. Histamine-induced increases in surface PrPC were attenuated following inhibition of the HRH2 receptor via the HRH2 antagonist ranitidine. These changes were unique to HRH2 activation, as stimulation of HRH1, HRH3, or HRH4 did not alter surface PrPC. Prolonged stimulation of HMC3 decreased PrPC expression following 48 and 72 hours of histamine stimulation. HMC3 cells can be stimulated by histamine to undergo intracellular calcium influx. Surface expression levels of PrPC on HMC3 cells are altered by histamine exposure, primarily mediated by HRH2. While histamine exposure also increases release of IL-6 and IL-8 in these cells, this cytokine release is not fully dependent on PrPC levels, as IL-6 release is only partially reduced and IL-8 release is unchanged under the conditions of HRH2 blockade that prevent PrPC changes. Overall, this suggests that PrPC may play a role in modulating microglial responses.

Objective: To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA). Methods: Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA. Results: After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P

Background: Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers. Methods: We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance. Results: Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores. Conclusions: Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.

Aims: This study investigated histamine intake and its associations with clinical and biochemical findings in patients with Behçet syndrome. Methods: Patients with Behçet syndrome were prospectively enrolled using a cross-sectional, multicenter, and online survey design. Sociodemographic parameters, including age, gender, smoking and alcohol intake, nutritional counseling history, anthropometric measurements, clinical characteristics, and biochemical results, were obtained using an online questionnaire. Dietary histamine intake was determined using a food frequency questionnaire. Results: The study included 66 patients (mean age: 37.5±11.3 years, women: 53%. Food consumption was reported to trigger oral aphthae in 81% of the individuals, and the most frequently reported triggers were eggplant (37.5%), tomatoes (37.5%), and citrus fruits (34.3%). There was a significant positive correlation between dietary histamine intake and white blood cell counts (r=0.650; p=0.050). There were no significant differences in the clinical characteristics, including oral aphthae, genital ulcers, uveitis, dermatologic lesions, gastrointestinal system involvement, joint involvement, and vascular involvement between patients with low and high dietary histamine intake. A positive correlation was found between dietary histamine intake and the frequency of attacks (r=0.324; p=0.008). Conclusions: This study showed that increased dietary histamine intake was associated with an increased frequency of attacks in patients with Behçet syndrome. Oral aphthae are associated with certain foods, such as eggplant, tomatoes, and citrus fruit.

ABSTRACT: Cheese is a food in which toxic concentrations of biogenic amines (BA) may be reached, mainly as a consequence of the decarboxylation of determined amino acids by certain lactic acid bacteria (LAB). To maintain the food safety of cheese, environmentally friendly strategies are needed that specifically prevent the growth of BA-producing LAB and the accumulation of BA. The bacteriocins produced by LAB are natural compounds with great potential as food biopreservatives. This work examines the antimicrobial potential of 7 bacteriocin-containing, cell-free supernatants (CFS: coagulin A-CFS, enterocin A-CFS, enterocin P-CFS, lacticin 481-CFS, nisin A-CFS, nisin Z-CFS and plantaricin A-CFS) produced by LAB against 48 strains of the LAB species largely responsible for the accumulation of the most important BA in cheese, that is, histamine, tyramine, and putrescine. Susceptibility to the different CFS was strain-dependent. The histamine-producing species with the broadest sensitivity spectrum were Lentilactobacillus parabuchneri (the species mainly responsible for the accumulation of histamine in cheese) and Pediococcus parvulus. The tyramine-producing species with the broadest sensitivity spectrum was Enterococcus faecium, and Enterococcus faecalis and Enterococcus hirae were among the most sensitive putrescine producers. Nisin A-CFS was active against 31 of the 48 BA-producing strains (the broadest antimicrobial spectrum recorded). Moreover, commercial nisin A prevented biofilm formation by 67% of the BA-producing, biofilm-forming LAB strains. These findings underscore the potential of bacteriocins in the control of BA-producing LAB and support the use of nisin A as a food-grade biopreservative for keeping BA-producing LAB in check and reducing BA accumulation in cheese.

Background: Fish is considered an important food because it includes main nutrients (proteins, fats, and ash) and micronutrients (vitamins and minerals). The assessment of fish nutritional content data may offer crucial recommendations regarding freshwater fish consumption and preserving human well-being. Aim: Evaluate the safety and quality properties of Nasser Lake fish, Aswan, Egypt. Methods: A total of 250 samples, 50 of each Nile tilapia, Nile perch, Zander, Catfish, and Elephant-snout, from Nasser Lake, Aswan, Egypt; beheaded, eviscerated, filleted, and minced for determination of proximate analysis, amino acid, fatty acids, minerals and heavy metal, histamine content, cholesterol content, and sensory assessment. Results: The proximate analysis showed that all the samples examined were of good protein sources, with mean values ranging from 15.92% to 22.89%. Nile perch exhibits the highest levels of total fatty acids and amino acids. Heavy metal concentrations varied considerably among the analyzed samples, with a significant variance in the detection of metals among the examined fish. The findings show low histamine and cholesterol levels in the examined species, and were in accordance with those set by the National Food Safety Authority (NFSA) and the European Union Commission (EC). Accordingly, all samples are accepted based on their sensory properties. Conclusion: Nasser Lake fish are of high nutritional value and have an excellent supply of amino and fatty acids. [Open Vet J 2024; 14(6.000): 1403-1416]

Abstract Introduction The development of several experimental migraine provocation models has significantly contributed to an understanding of the signaling mechanisms of migraine. The early history of this development and a view to the future are presented as viewed by the inventor of the models. Methods Extensive knowledge of the literature was supplemented by scrutiny of reference lists. Results Early studies used methodologies that were not blinded. They suggested that histamine and nitroglycerin (Glyceryl trinitrate, GTN) could induce headache and perhaps migraine. The development of a double blind, placebo-controlled model, and the use of explicit diagnostic criteria for induced migraine was a major step forward. GTN, donor of nitric oxide (NO), induced headache in people with- and without migraine as well as delayed migraine attacks in those with migraine. Calcitonin gene-related peptide (CGRP) did the same, supporting the development of CGRP antagonists now widely used in patients. Likewise, pituitary adenylate cyclase activating peptide (PACAP) provoked headache and migraine. Recently a PACAP antibody has shown anti migraine activity in a phase 2 trial. Increase of second messengers activated by NO, CGRP and PACAP effectively induced migraine. The experimental models have also been used in other types of headaches and have been combined with imaging and biochemical studies. They have also been used for drug testing and in genetic studies. Conclusion Conclusion. Human migraine provocation models have informed about signaling mechanisms of migraine leading to new drugs and drug targets. Future use of these models in imaging-, biochemistry- and genetic studies as well as in the further study of animal models is promising.

Abstract Memory retrieval can become difficult over time, but it is important to note that memories that appear to be forgotten might still be stored in the brain, as shown by their occasional spontaneous retrieval. Histamine in the central nervous system is a promising target for facilitating the recovery of memory retrieval. Our previous study demonstrated that histamine H3 receptor (H3R) inverse agonists/antagonists, activating histamine synthesis and release, enhance activity in the perirhinal cortex and help in retrieving forgotten long-term object recognition memories. However, it is unclear whether enhancing histaminergic activity alone is enough for the recovery of memory retrieval, considering that H3Rs are also located in other neuron types and affect the release of multiple neurotransmitters. In this study, we employed a chemogenetic method to determine whether specifically activating histamine neurons in the tuberomammillary nucleus facilitates memory retrieval. In the novel object recognition test, control mice did not show a preference for objects based on memory 1 week after training, but chemogenetic activation of histamine neurons before testing improved memory retrieval. This selective activation did not affect the locomotor activity or anxiety-related behavior. Administering an H2R antagonist directly into the perirhinal cortex inhibited the recovery of memory retrieval induced by the activation of histamine neurons. Furthermore, we utilized the Barnes maze test to investigate whether chemogenetic activation of histamine neurons influences the retrieval of forgotten spatial memories. Control mice explored all the holes in the maze equally 1 week after training, whereas mice with chemogenetically activated histamine neurons spent more time around the target hole. These findings indicate that chemogenetic activation of histamine neurons in the tuberomammillary nucleus can promote retrieval of seemingly forgotten object recognition and spatial memories.

Abstract Background Patients suffering from chronic spontaneous urticaria (CSU) are typically classified as type I or type IIb autoimmune CSU, but further patient stratification is hindered by the lack of biomarkers. Objectives We investigated whether the histamine content of individual basophils differ between patient subtypes in CSU to evaluate its potential as a biomarker. Methods A total of 101 patients diagnosed with CSU were included in the study. The histamine content per circulating basophil was derived from the basophil count in peripheral blood and levels of total cellular blood histamine. These measures, together with results from the serum‐induced basophil histamine release assay (s‐BHRA), were correlated to information on demographics, clinical characteristics, patient reported outcomes and laboratory analyses. Results The histamine content per basophil was significantly different between s‐BHRA positive and ‐negative patients (0.175 vs. 1.40 pg/cell, p

The majority of somatosensory DRG neurons express GABAA receptors (GABAAR) and depolarise in response to its activation based on the high intracellular chloride concentration maintained by the Na-K-Cl cotransporter type 1 (NKCC1). The translation of this response to peripheral nerve terminals in people is so far unclear. We show here that GABA (EC50 = 16.67μM) acting via GABAAR produces an influx of extracellular calcium in approximately 20% (336/1720) of isolated mouse DRG neurons. In contrast, upon injection into forearm skin of healthy volunteers GABA (1mM, 100μl) did not induce any overt sensations nor a specific flare response and did not sensitize C-nociceptors to slow depolarizing electrical sinusoidal stimuli. Block of the inward chloride transporter NKCC1 by furosemide (1mg/100μl) did not reduce electrically evoked pain ratings nor did repetitive GABA stimulation in combination with an inhibited NKCC1 driven chloride replenishment by furosemide. Finally, we generated a sustained period of C-fiber firing by iontophoretically delivering codeine or histamine to induce tonic itch. Neither the intensity nor the duration of histamine or codeine itch was affected by prior injection of furosemide. We conclude that although GABA can evoke calcium transients in a proportion of isolated mouse DRG neurons, it does not induce or modify pain or itch ratings in healthy human skin even when chloride gradients are altered by inhibition of the sodium coupled NKCC1 transporter. [ABSTRACT FROM AUTHOR]