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Histamine producing foodborne pathogens pose a major microbiological risk in the overall seafood products. Specifically, negative health effects of histamine poisoning from seafood products after processing is a food safety and human health concern globally. Therefore, it is essential to advance sustainable and inexpensive post-harvest processing strategies to counter this serious food safety and health challenge and to improve overall food quality of common seafood product like tuna fish. Based on these food safety and health quality needs, the aim of this study was to investigate the effectiveness of the combination of Lactiplantibacillus plantarum BY-45 and salt concentration to control histamine formation in vitro and in vivo on sample filet of tuna fish during processing to reduce this microbiological associated health risk. Isolation and identification of histamine forming bacteria in tuna loin and optimal storage temperature for inhibiting histamine formation was determined with L. plantarum BY-45 treatment. In this study, Escherichia coli belonging to Enterobacteriaceae family was found to be the predominant histamine forming bacteria contaminating our tuna samples. This contamination was suspected to happen during handling after catch and prior to landing at Benoa harbor, Bali for further processing. However, the rate of histamine formation was significantly suppressed (

The present work intends to provide a closer look at histamine in Drosophila. This choice is motivated firstly because Drosophila has proven over the years to be a very simple, but powerful, model organism abundantly assisting scientists in explaining not only normal functions, but also derangements that occur in higher organisms, not excluding humans. Secondly, because histamine has been demonstrated to be a pleiotropic master molecule in pharmacology and immunology, with increasingly recognized roles also in the nervous system. Indeed, it interacts with various neurotransmitters and controls functions such as learning, memory, circadian rhythm, satiety, energy balance, nociception, and motor circuits, not excluding several pathological conditions. In view of this, our review is focused on the knowledge that the use of Drosophila has added to the already vast histaminergic field. In particular, we have described histamine’s actions on photoreceptors sustaining the visual system and synchronizing circadian rhythms, but also on temperature preference, courtship behavior, and mechanosensory transmission. In addition, we have highlighted the pathophysiological consequences of mutations on genes involved in histamine metabolism and signaling. By promoting critical discussion and further research, our aim is to emphasize and renew the importance of histaminergic research in biomedicine through the exploitation of Drosophila, hopefully extending the scientific debate to the academic, industry, and general public audiences.

Background & Aims: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and in maintaining stomach homeostasis. Methods: Here, we expand on this role using histidine decarboxylase knockout (Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice, germ-free Hdc-/- mice, and bone-marrow–transplanted Hdc-/- mice. The stomach macrophage populations and function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA sequencing analysis on Hdc+/+ and Hdc-/- stomach tissues. Results: Single-cell RNA sequencing and flow cytometry of the stomach cells of Hdc-/- mice showed alterations in the ratios of 3 distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHC class IIhighCD74high). Tissue macrophages of the stomachs of Hdc-/- mice showed impaired phagocytic activity, increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/- mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. Conclusions: This study showed the importance of histamine signaling in tissue macrophage differentiation and maintenance of gastric homeostasis through the suppression of bacterial overgrowth in the stomach.

Seafood is one of the essential sources of nutrients for the human diet. However, they can be subject to contamination and can cause foodborne illnesses, including scombroid fish poisoning caused by histamine. Many microorganisms can produce enzymes that eventually decompose endogenous histidine to histamine in postmortem fish muscles and tissues. One of these is histamine-forming bacteria (HFB), primarily found in the gills, gut, and skin of fishes. Previous studies linked a plethora of Gram-negative HFB including Morganella spp. and Photobacterium spp. to scombroid fish poisoning from many types of seafood, especially the Scombridae family. These bacteria possess the hdc gene to produce histidine decarboxylase enzyme. It was reported that Gram-negative HFB produced 6345 ppm in tuna and 1223 ppm in Spanish mackerel. Interestingly, Gram-positive HFB have been isolated in the seafood samples with lower histamine levels. It suggests that Gram-negative HFB are the major contributor to the accumulation of histamine in seafood. Several analytical methods are available to detect and identify HFB and their histamine metabolites from seafood substrates. Rapid test kits can be used in food production settings for early detection of histamine to avoid food intoxication. Furthermore, high hydrostatic pressure and irradiation treatment could prevent the proliferation of HFB and inactivate the existing histidine decarboxylase (HDC) activity. As demonstrated in different seafood model systems, the HDC activity was deactivated at a maximum high hydrostatic pressure level of 400 MPa. The complete inactivation of HFB was achieved by gamma irradiation at a dose of 4.0 kGy. Other postharvest treatments, like enzymatic degradation and electrolyzed oxidizing water, were studied as sustainable methods for bacterial growth prevention and enzyme inactivation. However, other HFB react differently to these treatment conditions, and further studies are recommended.

Microbial dysbiosis plays an important role in the development of intestinal diseases. Recent studies suggest a link between intestinal bacteria and mammary cancer. Here, we report that female ApcMin/+ mice infected with Helicobacter hepaticus exhibited an increased mammary and small/large intestine tumor burden compared with uninfected littermates. H. hepaticus DNA was detected in small/large intestine, mammary tumors, and adjacent lymph nodes, suggesting a migration pathway. CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) infiltrated and expressed high levels of Wnts, likely enhancing tumorigenesis through activation of Wnt/β-catenin pathway. Our previous studies indicated that histidine decarboxylase (Hdc) marks a population of myeloid-biased hematopoietic stem cells and granulocytic MDSCs. Cytokines/chemokines secreted by IL-17-expressing mast cells and tumor tissues promoted Hdc+ MDSCs expansion and trafficking toward mammary tumors. Adoptive transfer of MDSCs isolated from H. hepaticus-infected mice increased MDSCs frequencies in peripheral blood, mesenteric lymph nodes, mammary gland, and lymph nodes in recipient ApcMin/+ mice. The adoptive transfer of H. hepaticus primed MDSCs also increased the size and number of mammary tumors. Our results demonstrate that H. hepaticus can translocate from the intestine to mammary tissues to promote mammary tumorigenesis with MDSCs. Targeting bacteria and MDSCs may be useful for the prevention and therapy of extraintestinal cancers.Abbreviations: Helicobacter hepaticus, Hh; myeloid-derived suppressor cell, MDSC; histidine decarboxylase, Hdc; Breast cancer, BC; T regulatory, TR; inflammatory bowel disease, IBD; fluorescence in situ hybridization, FISH; myeloid-biased hematopoietic stem cells, MB-HSCs; granulocytic MDSCs, PMN-MDSCs; Lipopolysaccharide, LPS; Toll-like receptors, TLRs; Mast cells, MCs; Granulocyte-macrophage colony-stimulating factor, GM-CSF; epithelial–mesenchymal transition, EMT; Intestinal epithelial cells, IECs.

Abstract Background Biogenic histamine plays an important role in immune response, neurotransmission, and allergic response. Although endogenous histamine production has been extensively studied, the contributions of histamine produced by the human gut microbiota have not been explored due to the absence of a systematic annotation of histamine-secreting bacteria. Results To identify the histamine-secreting bacteria from in the human gut microbiome, we conducted a systematic search for putative histamine-secreting bacteria in 36,554 genomes from the Genome Taxonomy Database and Unified Human Gastrointestinal Genome catalog. Using bioinformatic approaches, we identified 117 putative histamine-secreting bacteria species. A new three-component decarboxylation system including two colocalized decarboxylases and one transporter was observed in histamine-secreting bacteria among three different phyla. We found significant enrichment of histamine-secreting bacteria in patients with inflammatory bowel disease but not in patients with colorectal cancer suggesting a possible association between histamine-secreting bacteria and inflammatory bowel disease. Conclusions The findings of this study expand our knowledge of the taxonomic distribution of putative histamine-secreting bacteria in the human gut.

Background and Objectives: The possible adverse effect of histamine on human health has made it a detrimental aspect to the quality and safety of many fermented food products especially fish sauce. Materials and Methods: In the present study, hdcA gene in Staphylococcus epidermidis TYH1 was knocked out and its effect on histamine production was evaluated. HdcA encodes histidine decarboxylase, an enzyme that produces histamine from histidine. Both strains of TYH1, the wild type (WT) and mutant (∆hdcA) were then incubated in tryptic soy broth (TSB) supplemented with histidine (0.5 mM). The histamine content determined by capillary zone electrophoretic (CZE) analysis. Safety assessment of this mutant of food origin was conferred by virulence genes. Results: It was found that S. epidermidis TYH1 exhibited production of histamine (50.09 ± 0.06 μg/mL), while ∆hdcA strain of TYH1 exhibited no histamine forming activity. Safety assessment of ∆hdcA revealed the presence of nuc gene, while superantigenic toxins and coa genes were not observed. Therefore, it has the ability to be used as a starter culture to decrease the histamine content in any fermented food products. Conclusion: Our study findings may contribute to provide a novel approach of promoting the food safety of fish sauce and other fermented food products regarding the regulation of histamine content.

(1) Background: This study aims to elucidate a novel non-transcriptional action of IRF3 in addition to its role as a transcription factor in mast cell activation and associated allergic inflammation; (2) Methods: For in vitro experiments, mouse bone-marrow-derived mast cells (mBMMCs) and a rat basophilic leukemia cell line (RBL-2H3) were used for investigating the underlying mechanism of IRF3 in mast-cell-mediated allergic inflammation. For in vivo experiments, wild-type and Irf3 knockout mice were used for evaluating IgE-mediated local and systemic anaphylaxis; (3) Results: Passive cutaneous anaphylaxis (PCA)-induced tissues showed highly increased IRF3 activity. In addition, the activation of IRF3 was observed in DNP-HSA-treated mast cells. Phosphorylated IRF3 by DNP-HSA was spatially co-localized with tryptase according to the mast cell activation process, and FcεRI-mediated signaling pathways directly regulated that activity. The alteration of IRF3 affected the production of granule contents in the mast cells and the anaphylaxis responses, including PCA- and ovalbumin-induced active systemic anaphylaxis. Furthermore, IRF3 influenced the post-translational processing of histidine decarboxylase (HDC), which is required for granule maturation; and (4) Conclusion: Through this study, we demonstrated the novel function of IRF3 as an important factor inducing mast cell activation and as an upstream molecule for HDC activity.

Among biogenic amines, histamine is most frequently involved in foodborne intoxication. To evaluate histamine formation in tuna, several storage conditions were reproduced. An LC-MS/MS method was used for analytical determinations. Fresh tuna samples (not contaminated and grafted with tuna muscle naturally incurred with histamine at 6000 mg/kg) were stored at 4, 12, and 20 °C, and daily samples were collected for 6 days. The development of histamine was observed only in grafted tuna samples. At 4 °C, histamine formation progressed from 12.8 mg/kg (day 1) up to 68.2 mg/kg (day 6). At 12 °C, higher concentrations developed (23.9 mg/kg on day 1 up to 2721.3 mg/kg on day 6) relative to 20 °C (from 12.0 to 1681.0 mg/kg). It was found that at 4 °C, if grafted tuna was submerged in oil, histamine formation progressed more slowly. In a naturally contaminated sample, it was observed that the histamine distribution was uniform, while the normal cooking process did not affect the histamine level. Furthermore, it was found that the use of histamine-contaminated equipment for food handling may result in histamine formation in food. These results confirm the importance of implementing good hygiene practices and respecting the cold chain.

The physiological mechanisms underlying the complex interplay between life stressors and metabolic factors is receiving growing interest and is being analyzed as one of the many factors contributing to depressive illness. The brain histaminergic system modulates neuronal activity extensively and we demonstrated that its integrity is necessary for peripheral signals such as the bioactive lipid mediator oleoylethanolamide (OEA) to exert its central actions. Here, we investigated the role of brain histamine and its interaction with OEA in response to chronic social defeat stress (CSDS), a preclinical protocol widely used to study physio-pathological mechanisms underlying symptoms observed in depression. Both histidine decarboxylase null (HDC−/-) and HDC+/+ mice were subjected to CSDS for 21 days and treated with either OEA or vehicle daily, starting 10 days after CSDS initiation, until sacrifice. Undisturbed mice served as controls. To test the hypothesis of a histamine-OEA interplay on behavioral responses affected by chronic stress, tests encompassing the social, ethological and memory domains were used. CSDS caused cognitive and social behavior impairments in both genotypes, however, only stressed HDC+/+ mice responded to the beneficial effects of OEA. To detect subtle behavioral features, an advanced multivariate approach known as T-pattern analysis was used. It revealed unexpected differences of the organization of behavioral sequences during mice social interaction between the two genotypes. These data confirm the centrality of the neurotransmitter histamine as a modulator of complex behavioral responses and directly implicate OEA as a protective agent against social stress consequences in a histamine dependent fashion.

Primarily formed by the microbial decarboxylation of the amino acid histidine, histamine is the leading global cause of food poisoning from fish consumption worldwide. In the present work, the quality of 12 fresh and 12 frozen marketed sardines (Sardinella brasiliensis) were evaluated for histamine concentration using High-performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD), while the detection and quantification of histamine-producing bacteria were performed via quantitative Polymerase Chain Reaction (qPCR), and the microbiota composition of sardines was assessed through amplification of the 16S rRNA gene using high-throughput sequencing (HTS). According to the results obtained by HPLC-DAD, histamine concentration ranged from 226.14 to 583.87 mg kg−1. The histidine decarboxylase (hdc) genes from gram-negative bacteria (Morganella morganii, and Enterobacter aerogenes) were identified. The most abundant microorganisms present in fresh sardines belong to the genera Macrococcus spp., Acinetobacter spp., and Pseudomonas spp., while the genera Phyllobacterium spp., Pseudomonas spp., and Acinetobacter spp. were most abundant in frozen sardines.

Although Myrciaria dubia (camu-camu) has been shown to exert anti-oxidant and anti-inflammatory effects in both in vitro and in vivo studies, its use in allergic responses has not been elucidated. In the present study, the anti-allergic effect of 70% ethanol camu-camu fruit extract was tested on calcium ionophore (A23187)-induced allergies in RBL-2H3 cells. The RBL-2H3 cells were induced with 100 nM A23187 for 6 h, followed by a 1 h camu-camu fruit extract treatment. A23187 sanitization exacerbated mast cell degranulation; however, camu-camu fruit extract decreased the release of histamine and β-hexosaminidase, which are considered as key biomarkers in cell degranulation. Camu-camu fruit extract inhibited cell exocytosis by regulating the calcium/nuclear factor of activated T cell (NFAT) signaling. By downregulating the activation of mitogen-activated protein kinase (MAPK) signaling, camu-camu fruit extract hindered the activation of both histamine H1 and H4 receptors and inhibited histidine decarboxylase (HDC) expression by mediating its transcription factors KLF4/SP1 and GATA2/MITF. In A23187-induced ROS overproduction, camu-camu fruit extract activated nuclear factor erythroid-2-related factor 2 (Nrf2) to protect mast cells against A23187-induced oxidative stress. These findings indicate that camu-camu fruit extract can be developed to act as a mast cell stabilizer and an anti-histamine. This work also “opens the door” to new investigations using natural products to achieve breakthroughs in allergic disorder treatment.

Myocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In this study, using Hdc-deficient mice (Hdc−/− mice), we established an acute myocardial infarction mouse model to explore the potential roles of Hdc/histamine in cardiac immune responses. Comprehensive analysis was performed on the transcriptomes of infarcted hearts. Differentially expressed gene (DEG) analysis identified 2126 DEGs in Hdc-deficient groups and 1013 in histamine-treated groups. Immune related pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we used the ssGSEA algorithm to evaluate 22 kinds of infiltrated immunocytes, which indicated that myeloid cells and T memory/follicular helper cells were tightly regulated by Hdc/histamine post MI. The relationships of lncRNAs and the Gene Ontology (GO) functions of protein-coding RNAs and immunocytes were dissected in networks to unveil immune-associated lncRNAs and their roles in immune modulation after MI. Finally, we screened out and verified four lncRNAs, which were closely implicated in tuning the immune responses after MI, including ENSMUST00000191157, ENSMUST00000180693 (PTPRE-AS1), and ENSMUST-00000182785. Our study highlighted the HDC-regulated myeloid cells as a driving force contributing to the government of transmission from innate immunocytes to adaptive immunocytes in the progression of the injury response after MI. We identified the potential role of the Hdc/histamine-lncRNAs network in regulating cardiac immune responses, which may provide novel promising therapeutic targets for further promoting the treatment of ischemic heart disease.

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically (Hdc−/− mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the H3R agonist (VUF16839) impaired both STM and LTM. H3R agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the H3R with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both Hdc−/− and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after H3R stimulation are probably related to their function as heteroreceptors on cholinergic neurons.

Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R) or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC) mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI)-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.

Allergy is an immunological disorder that develops in response to exposure to an allergen, and histamines mediate these effects via histidine decarboxylase (HDC) activity at the intracellular level. In the present study, we developed a 3D model of Klebsiella pneumoniae histidine decarboxylase (HDC) and analyzed the HDC inhibitory potential of cinnamaldehyde (CA) and subsequent anti-allergic potential using a bacterial and mammalian mast cell model. A computational and in vitro study using K. pneumonia revealed that CA binds to HDC nearby the pyridoxal-5′-phosphate (PLP) binding site and inhibited histamine synthesis in a bacterial model. Further study using a mammalian mast cell model also showed that CA decreased the levels of histamine in the stimulated RBL-2H3 cell line and attenuated the release of β-hexoseaminidase and cell degranulation. In addition, CA treatment also significantly suppressed the levels of pro-inflammatory cytokines TNF-α and IL-6 and the nitric oxide (NO) level in the stimulated mast cells. A gene expression and Western blotting study revealed that CA significantly downregulated the expressions of MAPKp38/ERK and its downstream pro-allergic mediators that are involved in the signaling pathway in mast cell cytokine synthesis. This study further confirms that CA has the potential to attenuate mast cell activation by inhibiting HDC and modifying the process of allergic disorders.

Histamine is a critical mediator of IgE/mast cell-mediated anaphylaxis, a neurotransmitter and a regulator of gastric acid secretion. Histamine is a monoamine synthesized from the amino acid histidine through a reaction catalyzed by the enzyme histidine decarboxylase (HDC), which removes carboxyl group from histidine. Despite the importance of histamine, transcriptional regulation of HDC gene expression in mammals is still poorly understood. In this review, we focus on discussing advances in the understanding of molecular regulation of mammalian histamine synthesis.

Histamine is a well-known mediator of inflammation that is released from mast cells and basophils. To date, many studies using histamine receptor antagonists have shown that histamine acts through four types of receptors: H1, H2, H3, and H4. Thus, histamine plays more roles in various diseases than had been predicted. However, our knowledge about histamine-producing cells and the molecular mechanisms underlying histamine production at inflammatory sites is still incomplete. The histamine producing enzyme, histidine decarboxylase (HDC), is commonly induced at inflammatory sites during the late and chronic phases of both allergic and non-allergic inflammation. Thus, histamine levels in tissues are maintained at effective concentrations for hours, enabling the regulation of various functions through the production of cytokines/chemokines/growth factors. Understanding the regulation of histamine production will allow the development of a new strategy of using histamine antagonists to treat inflammatory diseases.

Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues modulates tumor immunity. We found that a transient histamine synthesis was induced in CD11b+Gr-1+ splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-γ were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-γ production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-γ production. However, suppression of IFN-γ production by these antagonists was also found when splenocytes were derived from the Hdc−/− BALB/c mice. Suppressive effects of these antagonists were found on IFN-γ production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H1 and H2 receptors, but not H3 and H4 receptors. IFN-γ production in the Hh1r−/− splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide can suppress IFN-γ production in activated splenocytes in a histamine-independent manner.

Background: The therapeutic use of Kampo medicine, Sho-seiryu-to (SST) in allergic disorders is well known. As histamine plays a central role in allergic diseases, it is possible that SST affects the allergy-related histamine signaling. In this study, we investigated the effect of SST on allergy-related histamine signaling in the nasal mucosa of toluene 2, 4-diisocyanate (TDI)-sensitized nasal allergy model rats. Methods: Six-week-old male, Brown Norway rats were sensitized for 2 weeks with 10 μl of 10% TDI, and after a 1 week interval, provocation was initiated with the same amount of TDI. SST (0.6 g/rat) was given orally 1 hour before TDI treatment began for a period of 3 weeks. Nasal symptoms were scored for 10 minutes immediately after TDI-provocation. The genes expression in nasal mucosa was determined using real-time quantitative RT-PCR. Results: SST significantly suppressed TDI-induced nasal allergy-like symptoms. TDI provocation showed a significant up-regulation of histamine H1 receptor (H1R) and histidine decarboxylase (HDC) gene expressions. Prolonged pre-treatment of SST significantly suppressed the mRNA levels of H1R and HDC that was up-regulated by TDI. SST also suppressed TDI-induced interleukin (IL)-4 and IL-5 mRNA elevation. However, SST showed no significant effect for TDI-induced mRNA elevation of IL-13. Conclusions: These results demonstrate that SST alleviates nasal symptoms by the inhibition of histamine signaling through suppression of TDI-induced H1R and HDC gene up-regulation. SST also suppresses cytokine signaling through suppression of IL-4 and IL-5 gene expression. Suppression of histamine signaling may be a novel mechanism of SST in preventing allergic diseases.

Allergic transfusion reaction is an anomaly that develops within several hours of transfusion which is usually treated by antihistamine. In the present study, we are looking into daucosterol, an extract of Traditional Chinese Medicine (TCM) Cordyceps, as a potential inhibitor of histidine decarboxylase. The approach of molecular docking and Molecular Dynamics Simulation (MDS) on a traditional anti-inflammatory Chinese medicine gave an atomic insight of the inhibition. The daucosterol was binding with a ?G of -3.17 Kcal/mol, to inhibit histamine synthesis by binding to histidine decarboxylase, possibly via the flexible catalytic loop. Such inhibitors that were designed to block the flexibility of the catalytic loop are potential candidates for further drug development program.

Photobacterium damselae subsp. damselae (Pdd) is considered to be an emerging pathogen of marine fish and has also been implicated in cases of histamine food poisoning. In this study, eight strains isolated from mullets of the genera Mugil and Liza captured in the Ligurian Sea were characterized, and a method to detect histamine-producing Pdd from fish samples was developed. The histamine-producing potential of the strains was evaluated in culture media (TSB+) using a histamine biosensor. Subsequently, two strains were used to contaminate mackerel fillets (4 or 40 CFU/g), simulating a cross-contamination on the selling fish stalls. Sample homogenates were enriched in TSB+. The cultures were then inoculated on thiosulfate-citrate-bile salts-sucrose agar (TCBS) and the dark green colonies were cultured on Niven agar. The violet isolates were characterized using specific biochemical and PCR based tests. All Pdd strains were histamine producers, yielding concentration varying from 167 and 8977 µg/mL in TSB+ cultures incubated at 30 °C for 24 h. Pdd colonies were detected from the inoculated mackerel samples and their histidine decarboxylase gene was amplified using species-specific primer pairs designed for this study. The results indicate that mullets can be source of Pdd and the fish retailers needs to evaluate the risk posed by cross-contamination on the selling fish stalls.

Earlier studies in zebrafish have revealed that acutely given ethanol has a stimulatory effect on locomotion in fish larvae but the mechanism of this effect has not been revealed. We studied the effects of ethanol concentrations between 0.75% and 3.00% on 7-day-old larval zebrafish (Danio rerio) of the Turku strain. At 0.75-3% concentrations ethanol increased swimming speed during the first minute. At 3% the swimming speed decreased rapidly after the first minute, whereas at 0.75 and 1.5% a prolonged increase in swimming speed was seen. At the highest ethanol concentration dopamine levels decreased significantly after a 10-min treatment. We found that ethanol upregulates key genes involved in the biosynthesis of histamine (hdc) and dopamine (th1 and th2) following a short 10-min ethanol treatment, measured by qPCR. Using in situ hybridisation and immunohistochemistry, we further discovered that the morphology of the histaminergic and dopaminergic neurons and networks in the larval zebrafish brain was unaffected by both the 10-min and a longer 30-min treatment. The results suggest that acute ethanol rapidly decreases dopamine levels, and activates both forms or th to replenish the dopamine stores within 30 minutes. The dynamic changes in histaminergic and dopaminergic system enzymes occured in the same cells which normally express the transcripts. As both dopamine and histamine are known to be involved in the behavioural effects of ethanol and locomotor stimulation, these results suggest that rapid adaptations of these networks are associated with altered locomotor activity.

Histidine decarboxylase activity was investigated in 21 strains of lactic acid bacteria isolated from Argentinian wines. This activity is not widely distributed between them, and occurs significatively only in some strains of Lactobacillus hilgardii. L.hilgardii 5w was selected for the study on the basis of its constitutive expression. Glucose is necessary for histidine transport. Maximum activity is observed at 37°C and pH 4.0. Enzyme activity is inhibited by SO2 and ethanol at concentrations usually found in wine. L-matic acid and citric acid act as stimulators of the activity.