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Competing Interests: Declaration of competing interest none

Dual-enzyme co-embedded materials have shown high potential for achieving efficient detection due to the convenience of two-enzyme cascade reactions. Herein, we developed a dual-enzyme hybrid microsphere (HM) based biosensor to detect diamines (histamine was included for ease of description) in aquatic products. The HM was made from diamine oxidase, horseradish peroxidase, and copper phosphate through the biomineralization method. Under optimal conditions, the system displayed linear color response to histamine of different concentrations ranging from 0 to 200 μg/mL. The detection limit of histamine was 0.15 μg/mL, showing higher sensitivity than the two-step free enzyme assay. Moreover, the detection system exhibited good specificity to diamines. The method was used to detect diamines in commercial samples, and the results were compared with those measured by the high-performance liquid chromatography method. Overall, the proposed assay exhibited high potential in diamine quantification and was readily extended to other cascade enzymatic reaction-based detection strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

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.

We studied the effects of some nitrogen-containing, heterocyclic, and cyclic compounds on the rate of oxidative deamination of polyamines and putrescine in tissues with a high proliferation rate. For this purpose, the specific activities of the main enzymes of polyamine oxidative degradation - spermine oxidase (SMO), polyamine oxidase (PAO), and diamine oxidase (DAO) were determined using a cell-free test system from regenerating rat liver. The compounds methyl 2-(5-formylfuran-2-yl)benzoate and 2,7-bis-[2-(diethylamino)ethoxy]-9H-fluoren-9-one (and in the form of dihydrochloride) showed mainly activating effect on oxidative degradation of putrescine, spermidine, and spermine, which indirectly indicates their antiproliferative effect. Nitrogen-free compounds inhibited this process, thus exhibiting potentially carcinogenic properties. Correlations were calculated for activity of DAO, PAO, and SMO with 5 topological indices: Wiener (W), Rouvray (R), Balaban (J) in the Trinaistich modification, detour (Ip), and electropy (Ie). The highest dependence was noted for DAO and the Balaban index (R=-0.55), for PAO and the detour index (R=0.78), and for SMO and the electropy index (R=0.53). The remaining dependencies showed insignificant correlation strength., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Oral submucous fibrosis (OSMF), a potentially malignant disorder, is developed by progressive fibrous tissue deposition in connective tissue along with atrophy of oral mucosa. Histological sections also show the mast cell infiltration in submucosa which may indicate their possible role in this entity. Abundant availability of biochemicals in mast cells like histamine and serine proteases like chymase may be released and play specific pathways in the disease pathophysiology. Possibly, if the histamine release has some part to play, diamine oxidase may also be found to have a relationship as it metabolizes histamine. The present study is proposed to identify the presence of chymase, histamine, and diamine oxidase in both, serum as well as tissue by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) respectively. This study may provide probable insight into the mast cell-related chemicals and their association with OSMF., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Gharote H et al.)

The availability of more efficient analytical methods that answer the world's demands is a challenge and their development continues to be a difficult task. In this work the construction of an electrochemical cell, based on low-cost and accessible materials, that can be easily constructed and used for electroanalytical purposes, is described. Pencil leads were used as electrodes and a transparency sheet as the base. This cell was used as transducer for developing an amperometric biosensor for the quantification of histamine, which is the only biogenic amine regulated by law. The analysis was based on the use of diamine oxidase as biorecognition element, hexacyanoferrate(III) as electron-transfer mediator, and chronoamperometry, at +0.5 V during 100 s, to record the analytical signal. A linear relationship between histamine concentration and the analytical signal was established between 5.0 and 35 mg L -1 and a low limit of detection (1.0 mg L -1 ) was achieved. The analysis of different fish species (sardine and tuna) was performed, obtaining recovery values between 102% and 110%. The stability of the sensor is noteworthy: it maintained 95% of the initial analytical signal after 15 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Histamine intolerance (HIT) is frequently diagnosed in patients with polysymptomatic otherwise unexplained symptoms., Objectives: To exclude HIT by a single-blind placebo-controlled histamine challenge (SBPCHC), to study clinical features of patients with positive challenge, and to examine the predictability of HIT by biomarkers., Methods: SBPCHC was performed in 59 patients with suspected HIT. History and clinical data, including serum diamine oxidase (DAO) and histamine skin test wheal size of patients with positive versus negative SBPCHC, were compared., Results: Patients were predominantly middle-aged women (84.7%). Three-quarters reported improvement but never resolution of symptoms during a histamine-low diet. Histamine provocation was safe; only 1 patient was treated with antihistamines. Thirty-seven patients (62.7%) displayed symptoms to placebo. HIT was excluded in 50 patients (84.7%). Objective symptoms occurred in 4 of 59 cases (6.8%) after histamine but not after placebo challenge. These were diagnosed with "plausible HIT" because reactions occurring by chance could not be excluded. Another 5 patients (8.5%) were diagnosed with "possible HIT" after case-dependent detailed analysis. Patients with plausible/possible HIT had reported more gastrointestinal symptoms (P = .01), but comparable diet response and equal histamine skin prick test wheal sizes to those without HIT. Serum DAO activity tended to be lower in patients with HIT (P = .08), but was highly variable in those without, limiting its value as a biomarker., Conclusions: SBPCHC disproves HIT in the majority of patients. Placebo-controlled challenges are needed as placebo reactions were frequent. Gastrointestinal symptoms after food intake and reduced DAO levels are markers for HIT; however, specificity is not sufficient enough for making the diagnosis., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Lower urinary tract symptoms (LUTS) are highly prevalent, and their treatment is mainly focused on the control of symptoms. Histamine intolerance (HIT) has been related to a variety of systemic symptoms. DAO deficiency has been identified as a significant factor contributing to histamine intolerance (HIT). Preclinical evidence indicates the involvement of histamine in the lower urinary tract. This study aimed to assess the prevalence of diamine oxidase deficiency ( DAO ) in a prospective cohort of 100 patients with at least moderate LUTS. A genetic study of four single nucleotide polymorphisms (SNPs) (c.-691G>T, c.47C>T, c.995C>T, and c.1990C>G) was performed. HIT was found in 85.9% of patients. The prevalence of at least one minor allele in the SNPs analyzed was 88%, without gender differences. Storage symptoms were more intense in the presence of HIT as well as asthenia and neurological and musculoskeletal symptoms. The presence of minor alleles of the AOC1 gene was associated with a higher intensity of symptoms. Minor alleles from c.-691G>T and c.47C>T SNPs were also associated with a greater severity of obstructive symptoms. Thirty-one percent of patients presented the four SNPS with at least one associated minor allele. The relationship between HIT and LUTS in a mixed population of men and women found in this study supports further investigations to define the pathophysiology of histamine in LUTS.

Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient well-being. Histamine is naturally degraded in the small intestine by diamine oxidase (DAO). Hereditary or acquired DAO deficiency causes extracellular histamine accumulation, leading to symptoms similar to those of individuals diagnosed with FM. Thus, this study aimed to assess the efficacy of adding DAO supplementation for 8 weeks to their standard therapy. We randomly assigned 100 women with FM (age: 33-61 years) to the supplementation and control groups. The Fibromyalgia Impact Questionnaire (FIQ), the Pain Catastrophizing Scale (PCS), and intensity scales were applied for a series of clinical symptoms together with the Bristol scale to assess the added value of DAO supplementation. Patients in both groups were receiving complete pharmacological support but some differences in the number of subjects receiving analgesics, antidepressants, and anxiolytics was noted. Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire. Qualitatively, the patients assigned to the DAO treatment group had lower scores for fatigue, anxiety, depression, burning and for rumination, magnification, and helplessness.

Histamine intolerance (HIT) is a clinical condition caused by decreased intestinal degradation of ingested histamine, primarily due to reduced enzyme diamine oxidase (DAO) activity, leading to histamine accumulation and causing various clinical manifestations. The measurement of serum DAO is commonly used as the main diagnostic test for HIT, although its diagnostic use is still uncertain. In this retrospective study, we aimed to assess the validity of DAO determination in patients with clinically suspected HIT. We measured DAO levels in 249 patients with suspected HIT and 50 healthy adult controls without HIT-related problems. Based on five clinical criteria, we divided patients into two groups: high (all five inclusion criteria; 41 patients) and low probability of HIT (≤4 inclusion criteria; 208 patients). Patients with a "high probability of HIT" had the lowest DAO (median: 8 U/mL, IQR: 6-10) in comparison to patients with a "low probability of HIT (median: 10 U/mL, IQR: 7-16, p = 0.0006) and healthy controls (median: 18 U/mL, IQR: 14-22, p < 0.0001). The specificity and sensitivity for DAO levels < 3/< 10 U/mL (manufacturer's set cut-off) to discriminate between patients with ''high probability of HIT'' and healthy controls were 100%/92% and 2%/71%. On the other hand, the specificity and sensitivity to discriminate between patients with ''high probability of HIT'' and ''low probability of HIT'' were 97%/61% and 2%/71%, respectively. Serum DAO determination represents an additional asset to the diagnosis of HIT based on clinical evaluation and assessment, but the diagnosis should not solely rely on DAO measurements.

Symptoms of the disorders across the irritable bowel syndrome (IBS) spectrum include several different, usually postprandial, abdominal complaints. Up to date, dietary treatments of the IBS have neither been personalized nor diagnosed with sufficient scientific evidence. They have mostly been treated using 'one-size-fits-all' approaches. Such include exclusion diets, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and gluten-free diets, lactose-free diets, a diet recommended by the UK National Institute for Health and Care Excellence, and a wheat-free diet. The exact pathophysiology of IBS disorders across the spectrum is still unclear. However, the symptom profile of IBS spectrum disorders seems similar to that of food intolerance/malabsorption syndromes. Celiac disease, fructose malabsorption, histamine intolerance and lactose intolerance represent food intolerance/malabsorption disorders based on the indigestion of sugars and/or proteins. Helicobacter pylori infection may potentially promote the development of IBS and, when facing a case of IBS-like symptoms, a search for intolerance/malabsorption and H. pylori should be added to find the correct treatment for the respective patient. This review will discuss why the 'one-size-fits-all' dietary approach in the treatment of complaints across the IBS spectrum cannot be successful. Hence, it will provide an overview of the most common overall dietary approaches currently used, and why those should be discouraged. Alternatively, a noninvasive diagnostic workup of the pathophysiologic factors of food intolerance/malabsorption in each patient with symptoms of the IBS spectrum is suggested. Additionally, if H. pylori is found, eradication therapy is mandatory, and if food intolerance/malabsorption is detected, an individual and personalized dietary intervention by a registered dietician is recommended., Competing Interests: Declaration of competing interest Wolfgang J. Schnedl received speaking honoraria from Sciotec. The other authors have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Biogenic amines are synthesized through the bacterial decarboxylation of amino acids, commonly found in high levels in animal by-product meals due to spoilage. Furthermore, biogenic amines and other metabolites can be produced by the fermentation of proteins in the hindgut according to the protein source and concentration of crude protein (CP) in the diet. Thus, this study aimed to evaluate two protein sources (poultry by-product meal (PBPM) and hydrolyzed chicken liver powder (HCLP)) and three CP concentrations (24, 32, and 40%) and their effects on the consumption and fecal excretion of biogenic amines, plasma monoamine oxidase (MAO) and diamine oxidase (DAO) activities, and total antioxidant capacity (TAC) of healthy adult dogs after 30 days of feeding the experimental diets. Twelve dogs were randomly distributed into six treatments (n = 6/treatment): PBPM24 (PBPM with 24% CP); PBPM32 (PBPM with 32% CP); PBPM40 (PBPM with 40% CP); HCLP24 (HCLP with 24% CP); HCLP32 (HCLP with 32% CP); HCLP40 (HCLP with 40% CP). The PBPM and PBPM-based diets had higher concentrations of putrescine, cadaverine, tyramine, histamine, agmatine, and total biogenic amines. In contrast, HCLP and HCLP-based diets contained higher concentrations of spermidine, phenylethylamine, and spermine. The PBPM and PBPM-diets had higher biogenic amine index (BAI) indicating lower quality due to the high content of putrescine, cadaverine and tyramine. Dogs fed diets with PBPM and higher protein concentrations consumed more putrescine, cadaverine, tyramine, agmatine, and total amines ( p < 0.0001), while dogs fed with HCLP consumed more spermidine, phenylethylamine, and spermine ( p < 0.0001). Fecal excretion of phenylethylamine was greater in dogs fed HCLP32 and HCLP40 diets ( p = 0.045). Dogs fed with HCLP tended to excrete more spermidine and tryptamine via feces, while higher protein concentrations tended to increase fecal excretion of cadaverine ( p < 0.10). Plasma MAO activity was higher in dogs fed HCLP24 and PBPM32 diets ( p = 0.024). The plasma activities of DAO and TAC were not different between diets ( p > 0.05). Although we did not evaluate the intestinal activities of MAO and DAO, our results suggest that healthy adult dogs have an efficient deamination process on the gut epithelium.

Objective: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD)., Methods: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice., Results: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05)., Conclusions: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The elevated circulating toxins secondary to the impairment of intestinal barrier integrity commonly elicit a chronic inflammatory response and finally contribute to multiple diseases. These toxins, including bacterial by-products and heavy metals, are the potent risk factors for the development of recurrent spontaneous abortion (RSA). Preclinical evidence suggests that several dietary fibers can restore intestinal barrier function and decrease the accumulation of heavy metals. However, it is uncertain whether treatment with a newly developed blend of dietary fibers product (Holofood) benefits patients with RSA., Methods: In this trial, we enrolled 70 adult women with RSA, who were randomly assigned into the experiment group and the control group in a 2:1 ratio. Upon the basis of conventional therapy, subjects in the experiment group (n = 48) received 8 weeks oral administration with Holofood three times daily at a dose of 10 g each time. Subjects without Holofood consumption were set as the control (n = 22). Blood samples were collected for the determinations of metabolic parameters, heavy mental lead, and the indices related to intestinal barrier integrity (D-lactate, bacterial endotoxin, and diamine oxidase activity)., Results: The reduction amplitude in blood lead from baseline to week 8 was 40.50 ± 54.28 (μg/L) in the experiment group as compared with 13.35 ± 36.81 (μg/L) in the control group (P = 0.037). The decreased level of serum D-lactate from baseline to week 8 was 5.58 ± 6.09 (mg/L) in the experiment group as compared with - 2.38 ± 8.90 (mg/L, P < 0.0001) in the control group. The change in serum DAO activity from baseline to week 8 was 3.26 ± 2.23 (U/L) in the experiment group as compared with - 1.24 ± 2.22 (U/L, P < 0.0001) in the control group. Participants who received Holofood had a greater decline in blood endotoxin from baseline to week 8 than those in the control group. Moreover, by comparing with the self-baseline, Holofood consumption significantly decreased the blood levels of lead, D-lactate, bacterial endotoxin, and DAO activity., Conclusion: Our results suggest that Holofood affords a clinically relevant improvements in blood lead level and intestinal barrier dysfunction in patients with RSA., (© 2023. The Author(s).)

Histamine intolerance (HIT) is a common adverse reaction to food where elimination and reintroduction of histamine-rich food is part of the investigation. Analysis of the enzyme diamine oxidase (DAO) is sometimes used as an additional tool for diagnosis. This study aimed to describe the distribution of DAO in a large representative cohort of adults and to determine the association between DAO activity and possible associated factors. The study is based on the population-based West Sweden Asthma Study and includes 1051 subjects. Subjects underwent structured interviews including questions on demography, asthma, allergy symptoms, and lifestyle factors. Subjects were assessed for specific-IgE-antibodies and measurement of DAO activity in serum. Previously suggested cut-off levels for low values (<3 U/mL), normal values (>10 U/mL), and median levels of DAO were used. In the group of 1051 subjects, only a few presented reactions upon histamine intake, whereas 44% presented DAO levels below the suggested normal cut-off levels. BMI and age were shown to have an impact on DAO activity among women with increasing activity of DAO with increasing BMI and age. Among men, only increasing age was seen to have an impact on DAO levels. There was no difference in DAO levels with different sensitization status to common foods or airborne allergens. No association between DAO levels and reported symptoms to histamine-rich foods could be found. In conclusion, the determination of the DAO enzyme needs to be re-evaluated and may not be used as a valuable tool for histamine intolerance using current cut-off values. Further studies are needed to improve the use of DAO as a biomarker for histamine intolerance.

Introduction: The amine oxidase copper-containing 1 (AOC1) gene encodes for the diamine oxidase (DAO) enzyme. DAO is an enzyme that catabolizes some molecules, including histamine, and is the degradative enzyme in the polyamine catabolic pathway that is active in intestinal mucosal cells. Variants of AOC1 are associated with reduced DAO activity, resulting in accumulation of high levels of histamine and causing a wide range of neurological, gastrointestinal, and epidermal disorders, which are present in people with fibromyalgia. This study aimed to evaluate the impact of four AOC1 gene variants, namely, rs10156191, rs1049742, rs1049793, and rs2052129, on fibromyalgia symptoms measured by the Fibromyalgia Impact Questionnaire (FIQ), such as sleep disorders, atopic dermatitis, migraine, gastrointestinal (GI) disorders, allergies, and intolerances, in adult women with fibromyalgia. Methods: The sample consisted of 100 unrelated women with fibromyalgia between 33 and 60 years of age (48.48 years ±7.35), whose were diagnosed by a rheumatologist based on symptoms such as pain, stiffness, and fatigue. Single-nucleotide polymorphisms (SNPs) of AOC1 were identified using oral mucosa samples collected following a standard hygiene protocol. DNA was extracted, and gene variants of interest were analyzed using multiplex single-nucleotide primer extension (SNPE). Clinical data were collected using the FIQ and a series of variables that quantified the intensity and frequency of the symptoms. Results: The minor allele frequencies of rs10156191, rs1049742, rs1049793, and rs2052129 were 31.5, 10, 32.5, and 27%, respectively. Each variant was found to be in Hardy-Weinberg equilibrium, but partial linkage disequilibrium between AOC1 SNPs is suspected. The results show that fibromyalgia symptoms measured using the FIQ tend to increase with the number of risk alleles and that the intensity of dry skin and low stool consistency may be associated with an increase in the number of these alleles. Conclusion: This study constitutes the first step in investigating associations between fibromyalgia symptoms and candidate variants of the AOC1 gene in DAO enzyme activity. Identification of reduced DAO activity may improve the quality of life and treatment of symptoms in fibromyalgia patients., Competing Interests: TP, ER, AD, and IS belong to the scientific committee of the International Society for DAO Deficiency and have received fees for presentations at conferences. Authors GO, BP, GS, AT, SL, LT, and IS were employed by the CINUSA Group; authors TP and ER were employed by Grupo Vivo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Okutan, Perucho Alcalde, Ruiz Casares, Penadés, Sánchez Niño, Terrén Lora, López Oliva, Torrente Estríngana, Duelo and San Mauro Martín.)

The serum concentration and activity of diamine oxidase (DAO) in calves with or without diarrhea during the first month of life were examined. The serum DAO concentration was highest on day 0 after birth, and gradually decreased. No differences in serum DAO concentrations were observed between calves with diarrhea and control calves. In contrast, serum DAO activity was lowest on day 0 after birth, and gradually increased. Serum DAO activity in calves with diarrhea was lower than that in the control calves from day 20 after birth. These findings suggest that serum DAO activity and concentration are not correlated, and serum DAO activity is useful for assessing damage to the small intestinal mucosa in calves.

The neurotoxin β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim of this research is to study the toxicity of BMAA (0.1-1 mM) on mitochondria and submitochondrial particles with ATPase activity, on the semicarbazide-sensitive amino oxidases (SSAOs) activity of rat liver, and on an in vitro model containing functionally active excitable tissues-regularly contracting heart muscle preparation with a preserved autonomic innervation. For the first time the BMAA-dependent inhibition of SSAO activity, the elimination of the positive inotropic effect of adrenergic innervation, and the direct and reversible inhibition of adrenaline signaling in ventricular myocytes with 1 mM BMAA were observed. Additionally, it is confirmed that 1 mM BMAA can activate mitochondrial ATPase indirectly. It is concluded that a higher dose of BMAA may influence multiple physiological and pathological processes as it slows down the degradation of biogenic amines, downregulates the sympathetic neuromediation, and embarrasses the cell signaling of adrenergic receptors.

Azospirillum baldaniorum Sp 245 is a model plant growth-promoting rhizobacterium. The first cross-talk with plants takes place within the roots. Roots cells growth is constrained by the primary cell wall (CW). Also, neighboring CW form the apoplast that should affect cells signaling and biochemical messages. Studies on CW phenolic composition ferulate (FA), diferulates (DFA) and p-coumarate and polyamines (PA) metabolisms of A. baldaniorum Sp 245- inoculated roots and on bacterial PA production in culture media should help to understand more about the mechanisms involved in Azospirillum-root association. For this purpose, CW-bound FA, DFA and p-coumarate contents, putrescine (put) and spermidine contents, diamine and polyamine oxidases activities, and H2O2 content of Cucumis sativus roots from dark grown seedlings inoculated with A. baldaniorum Sp 245 were determined. Also, bacterial PA production under constant agitation or static conditions was evaluated. Results showed lesser contents of all phenolics, and higher FA/DFA ratio in CW of inoculated roots that should be responsible for roots growth promotion. Also, the increased put content, DAO activity, and H2O2 production in the roots should be associated to A. baldaniorum Sp 245 growth promotion in early stages. Finally, the participation of both PA in A. baldaniorum Sp 245 biofilm formation was demonstrated., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Idiopathic rhinitis represents more than 50% of non-allergic rhinitis, a heterogeneous group that involves the symptomatic inflammation of the nasal mucosa. The TRPV1 receptor of unmyelinated C-type neurons appears to be involved in its pathophysiology. Histamine, whose main catabolic enzyme is DAO, is one of the mediators that can activate this receptor. The failure of DAO causes an increase in the level of histamine in the body and, consequently, the activation of TRPV1. The objective was to investigate the existence of a DAO enzyme activity deficit in idiopathic rhinitis and its correlation with symptoms. A cross-sectional study was conducted in 116 idiopathic rhinitis patients, and DAO activity, nasal peak inspiratory flow, and rhinitis severity were recorded. The prevalence of a DAO activity deficit was 41.38% (95%CI 0.33−0.50; p = 0.05). The DAO activity in patients with mild rhinitis was 52.93 ± 8.72 HDU/mL, in those with moderate rhinitis it was 120.33 ± 71.63 HDU/mL, and in those with severe rhinitis it was 92.58 ± 27.75 HDU/mL (p = 0.006). The NPIF in patients with a DAO activity deficit was 107.92 ± 34.05 L/min, compared to 72.35 ± 27.16 L/min in patients with normal enzymatic activity (p < 0.001), demonstrating a linear correlation between activity levels and nasal obstruction (−0.45; p < 0.001). Therefore, patients with a DAO deficiency and idiopathic rhinitis could present a milder disease course, because the repeated and continuous activation of TRPV1 led to a partial or total decrease in their response (desensitization). This new theory represents a different perspective for the study of idiopathic rhinitis and its relationship with TRPV1, with the regulation or modulation of the desensitization of TRPV1 being an important therapeutic target for patients with idiopathic rhinitis in the future.

Passiflora edulis, commonly known as passion fruit, is a popular all-weather fruit eaten fresh or processed. Its shells, which currently are mostly discarded as waste and hurt the environment, account for more than half of the passion fruit. The shells contain gamma-aminobutyric acid (GABA) which is the main inhibitory neurotransmitter and has many proven medical values such as antidepressant, anti-anxiety, etc. Many studies have shown that GABA production in plants can be significantly increased by reverse stress. Taking Tainong 1 as a typical passion fruit cultivar, this study explored the optimal anoxic vacuum treatment for increasing the GABA content of passion fruit shells. The content increased to 2139.25 ± 26.69 mg/100 g on day 4 of chill storage after vacuum packing (63.68% higher than the control). The activities of glutamate decarboxylase (GAD) and diamine oxidase (DAO) were significantly higher in the vacuum-treated group than in the control group after 4 days of vacuum-chill storage. On day 5 of vacuum-chill storage, the activities of all measured enzymes decreased except for the increase of GABA transaminase (GABA-T), which was accompanied by a decrease in GABA content. Vacuum treatment and subsequent chill storage increased the content of GABA, thereby increasing functional value of passion fruit shells., (© 2022 Institute of Food Technologists.)

Aiming at enhancing the biosensing detection of histamine in foods at high temperature, we developed a thermoregulatory biosensor based on diamine oxidase-immobilized phase-change microcapsules consisting of an n-docosane core, a TiO 2 shell, and an electroactive polyaniline/ZnO composite coating layer. The microcapsules exhibit a satisfactory latent heat capacity of over 112 J/g for thermo-temperature regulation. Through an innovative integration of electroactive phase-change microcapsules and biological enzyme in the working electrode, the biosensor obtained a thermoregulatory function through reversible phase transitions by the n-docosane core under high-temperature environments. This enables the biosensor to achieve a higher response sensitivity of 28.57 µA⋅mM -1 ⋅cm -2 and a lower detection limit of 0.473 µmol/L at the high assay temperatures compared to conventional histamine biosensors. With enhanced electrochemical biosensing performance through in-situ thermo-temperature regulation, the smart biosensor developed in this study has found practical applications for high-sensitive detection and high-accurate quantitive determination of histamine in foods across a broad temperature range., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Allergic rhinitis (AR) is characterized by the increased sensitivity of the nasal mucosa to allergens and has a significant impact on life quality. There is promising evidence that biomarkers can help in the diagnosis, treatment, and follow-up of patients with AR. Diamine oxidase (DAO) is one of the enzymes responsible for the breakdown of histamine, the primary mediator of allergies., Objective: To investigate the significance of DAO as a useful biomarker for diagnosis and the severity of AR., Methods: In this case-control study, 24 patients and 24 healthy controls were recruited and their serum DAO levels, total IgE levels (using ELISA), blood eosinophil count, and percentage (using complete blood cell count) were measured. The sino-nasal outcomes test-22 (SNOT-22) questionnaire was used to assess the severity of symptoms in patients. The Receiver Operating Characteristic (ROC) analysis was used to assess the predictive power of DAO level for the diagnosis of AR. The relationship between DAO and disease severity, as well as other AR-related clinical factors, were also investigated., Results: DAO levels were lower in AR patients compared with the controls. The DAO level did not significantly correlate with the severity of AR according to the Allergic Rhinitis and its Impact on Asthma (ARIA) score, though it was lower in patients with persistent or moderate to severe symptoms. The total IgE, eosinophil percentage, and SNOT-22 score all had an inverse relationship with DAO. Moreover, DAO was significantly associated with the diagnosis of AR, with an Area under the ROC Curve (AUC) of 0.771, a sensitivity of 75%, and a specificity of 62.5%., Conclusion: DAO might be a valuable biomarker in the diagnosis of allergic rhinitis.

The disulfide-containing molecule cystamine and the thiosulfonate thiotaurine are of interest as therapeutics. Both are precursors of taurine, but the chemistry of their metabolism is not clear. The rates at which these molecules are metabolized is also unknown. The chemistry and rate constants have been determined for a process in which cystamine is converted in four reactions to thiotaurine. Cystamine is oxidized by diamine oxidase with a specificity constant comparable to other diamine substrates. The rapid hydrogen peroxide-mediated oxidation of cystaldimine yields reactive glyoxal and thiocysteamine, which quickly performs transsulfuration with hypotaurine. Thiotaurine reacts spontaneously with hydrogen peroxide to form taurine and sulfite, but it is 15-fold less reactive than hypotaurine as an antioxidant. An estimation of biological rates of reaction indicates that cystamine is likely to be oxidized by diamine oxidase in vivo, but its metabolic products will be diverted to molecules other than thiotaurine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The consumption of foods fraught with histamine can lead to various allergy-like symptoms if the histamine is not sufficiently degraded in the human body. The degradation occurs primarily in the small intestine, naturally catalyzed by the human diamine oxidase (DAO). An inherent or acquired deficiency in human DAO function causes the accumulation of histamine and subsequent intrusion of histamine into the bloodstream. The histamine exerts its effects acting on different histamine receptors all over the body but also directly in the intestinal lumen. The inability to degrade sufficient amounts of dietary histamine is known as the 'histamine intolerance'. It would be preferable to solve this problem initially by the production of histamine-free or -reduced foods and by the oral supplementation of exogenous DAO supporting the human DAO in the small intestine. For the latter, DAOs from mammalian, herbal and microbial sources may be applicable. Microbial DAOs seem to be the most promising choice due to their possibility of an efficient biotechnological production in suitable microbial hosts. However, their biochemical properties, such as activity and stability under process conditions and substrate selectivity, play important roles for their successful application. This review deals with the advances and challenges of DAOs and other histamine-oxidizing enzymes for their potential application as processing aids for the production of histamine-reduced foods or as orally administered adjuvants to humans who have been eating food fraught with histamine., (© 2022. The Author(s).)

Quantitation of urinary metabolites of histamine, prostaglandin D 2 , and leukotriene E 4 can fill the gap in our current efforts to improve diagnosis and management of symptomatic patients with systemic mastocytosis, and/or mast cell activation syndrome, In addition, patients symptomatic due to mast cell activation but who do not meet all the criteria for mast cell activation syndrome can have elevated baseline mediator metabolites. Serum tryptase levels have been the workhorse in diagnosing these disorders, but it has several drawbacks including the need to obtain acute and baseline samples, which require 2 visits to health care facilities and 2 venipunctures. Recently, increased baseline tryptase level has been reported in hereditary alpha tryptasemia, complicating diagnostic possibilities of an increased baseline tryptase level. Furthermore, no treatment can specifically be targeted at tryptase itself. In contrast, the finding of 1 or more elevated urinary levels of histamine, prostaglandin D 2 , and/or leukotriene E 4 metabolites (1) greatly narrows diagnostic possibilities for causes of symptoms; (2) informs the practitioner what specific metabolic pathways are involved; and (3) targets the treatment in a specific, direct fashion. As a bonus, baseline spot/random urine samples can be obtained by the patients themselves and repeated at exactly the correct time when symptoms occur., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The existing zymography method for the detection of diamine oxidase (DAO) activity has been improved by a new staining procedure with the aim to ameliorate its sensitivity. Both procedures used SDS-PAGE gels containing uniformly distributed entrapped peroxidase (that wouldn't migrate during electrophoresis). The new approach with 3,5-dichloro-2-hydroxybenzenesulfonate (DCHBS) as peroxidase substrate and with 4-amino-antipyrine as color stabilizer allows a more sensitive detection of DAO when compared to the previously reported o-phenylenediamine (o-PDA) as peroxidase substrate. The newly improved method appears faster, simple and environmentally friendly. It can be used for most of oxidases releasing hydrogen peroxide as reaction product., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A new diamine oxidase (DAO-1) was discovered recently in the yeast Yarrowia lipolytica PO1f and investigated for its histamine degradation capability under simulated intestinal conditions. DAO-1 was formulated together with catalase as a sucrose-based tablet. The latter (9 × 7 mm; 400 mg) contained 690 nkat of DAO-1 activity, which was obtained from a bioreactor cultivation of a genetically modified Y. lipolytica with optimized downstream processing. The DAO-1 tablet was tested in a histamine bioconversion experiment under simulated intestinal conditions in the presence of food constituents, whereby about 30% of the histamine was degraded in 90 min. This amount might already be sufficient to help people with histamine intolerance. Furthermore, it was found that the stability of DAO-1 in a simulated intestinal fluid is influenced distinctively by the presence of a food matrix, indicating that the amount and type of food consumed affect the oral supplementation with DAO. This study showed for the first time that a microbial DAO could have the potential for the treatment of histamine intolerance by oral supplementation.

The association between intestinal permeability and sarcopenia remains unclear, and few studies have mentioned the relationship between intestinal permeability and skeletal muscle strength. The present cross-sectional community study was conducted in a rural area of Beijing to explore the association between intestinal permeability and handgrip strength (HGS) in middle-aged and older adults. Serum lipopolysaccharide (LPS), diamine oxidase (DAO) and D-lactate were detected to evaluate intestinal permeability. Gut microbiota (GM) and its potential interaction were also analyzed in the decision tree model. HGS was negatively correlated with DAO (r = −0.396, p < 0.01) in males. The negative association between HGS and DAO remained significant with the adjustment of covariates (β = −1.401, p < 0.05). Serum DAO and LPS were both negatively associated with HGS in middle-aged and older males, with the significant interactions of GM in the decision tree model, and D-lactate showed a negative association with HGS in females. Therefore, intestinal permeability was associated with the loss of skeletal muscle strength in middle-aged and older adults, and serum DAO may be a novel predictor for the loss of skeletal muscle strength in middle-aged and older males.

Background/objectives: Histamine has shown a possible role in the etiopathogenesis of migraine. It has been reported an association between some polymorphisms in the diamine oxidase (DAO) gene and migraine, especially in women. Two studies addressing DAO activity in migraine patients showed conflicting results. We investigated the possible relationship of serum DAO activity and histamine levels and 3 polymorphisms in the DAO gene with the risk for migraine., Methods: We studied the frequencies of DAO rs10156191, rs1049742 and rs1049793 genotypes and allelic variants in 298 migraine patients and 360 healthy controls (using a TaqMan-based qPCR assay), and serum DAO activity and histamine levels in a subset of 99 migraine patients and 115 controls with strict exclusion criteria, and analysed the relationship of these variables with several clinical features of migraine., Results: The frequencies of the DAO genotypes and allelic variants analysed were similar in migraine patients and controls. Serum DAO activity was significantly higher in migraine patients (Vmax/Km 4.24 ± 2.93 vs. 3.60 ± 7.64, p < 0.001), especially in females (Vmax/Km 4.63 ± 2.96 vs. 3.18 ± 2.32, p < 0.0001), while serum histamine was similar in both study groups., Conclusion: Serum DAO activity was increased in patients with migraine, especially in females, while serum histamine levels were normal. None of the studied polymorphisms was associated with the risk for migraine., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Lactose intolerance (LIT) is one of the major causes of irritable bowel syndrome (IBS) spectrum complaints. Differences in inadequate lactose digestion are described as various LIT phenotypes with basically unknown pathophysiology. In LIT patients, we retrospectively assessed the effect of histamine intolerance (HIT) on expiratory hydrogen (H2) during H2 lactose breath tests. In a retrospective evaluation of charts from 402 LIT patients, 200 patients were identified as having only LIT. The other 202 LIT patients were found to additionally have diamine oxidase (DAO) values of <10 U/mL, which indicates histamine intolerance (HIT). To identify HIT, standardized questionnaires, low serum DAO values and responses to a histamine-reduced diet were used. Patients were separated into three diagnostic groups according to the result of H2 breath tests: (1) LIT, with an H2 increase of >20 parts per million (ppm), but a blood glucose (BG) increase of >20 mg/dL, (2) LIT with an H2 increase of 20 ppm in combination with a BG increase of <20 mg/dL, and (3) LIT with an exhaled H2 increase of <20 ppm and BG increase of <20 mg/dL. Pairwise comparison with the Kruskal Wallis test was used to compare the areas under the curve (AUC) of LIT and LIT with HIT patients. Exhaled H2 values were significantly higher in H2 > 20 ppm and BG < 20 mg/dL patients with LIT and HIT (p = 0.007). This diagnostic group also showed a significant higher number of patients (p = 0.012) and a significant higher number of patients with gastrointestinal (GI) symptoms during H2 breath tests (p < 0.001). Therefore, low serum DAO values, indicating HIT, influence results of lactose tolerance breath tests.

Background: Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment. Methods: We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3−10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment. Results: A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3−10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33−60%) when compared to patients with low DAO (40%, IQR = 20−60%; p = 0.045) or high DAO (33%, IQR = 0−50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels. Conclusions: HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.

In patients with histamine intolerance accumulated or ingested histamine causes a broad range of undesirable symptoms. Food-derived histamine is degraded by intestinal diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), while the organic cation transporter 3 (OCT3) contributes to the transcellular flux of histamine. Anecdotal evidence from patients with HIT suggests an improvement of symptoms related to histamine intolerance after intake of Ze 339, a lipophilic CO 2 -extract prepared from the leaves of Petasites hybridus. Thus, it was the aim of this study to investigate the influence of Ze 339 on DAO, HNMT and OCT3 using Caco-2 and MDCKII cells. Even though Ze 339 reduced mRNA levels of HNMT and DAO, there was no change in protein expression. Ze 339 changed neither the basal release nor the enzymatic activity of DAO. Testing the interaction of Ze 339 with the transcellular histamine transport, we observed a significant increase in the basal to apical flux in presence of high Ze 339 concentrations at the early phases of the experiment. Testing the influence of Ze 339 on OCT3-mediated histamine uptake in overexpressing MDCKII cells revealed a dose-dependent inhibition with an estimated IC 50 of 26.9 ug/mL for the extract. In conclusion, we report an effect of Ze 339 on transcellular histamine transport, where inhibition of OCT3 may contribute., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Infection with Helicobacter pylori ( H.pylori ) may cause dyspepsia and/or unexplained functional nonspecific, gastrointestinal complaints of the irritable bowel syndrome (IBS) spectrum. Hitherto, in H. pylori infected patients with symptoms of the IBS spectrum the occurrence of additional food intolerance/malabsorption is not evaluated. We used a retrospective analysis of charts from 548 patients who presented with gastrointestinal complaints of the irritable bowel syndrome spectrum. An enzyme-linked IgA immunosorbent assay or histologic evaluation of gastric mucosa were used to detect H. pylori infection. A hydrogen breath (H 2 ) test was performed to evaluate fructose malabsorption (FM) and lactose intolerance (LIT). Serum diamine oxidase value of <10 U/ml and a response to a histamine-reduced diet was used to identify histamine intolerance (HIT). We found 293 patients infected with H. pylori , within these were 58 H. pylori patients with LIT, 23 H. pylori LIT patients with FM and 46 H. pylori LIT patients with HIT. Additionally, 13 H. pylori, lactose- and histamine intolerance patients also had FM. The Kruskal Wallis test and pairwise comparison were used to analyze differences of the area under the curve of expiratory hydrogen. In lactose H 2 breath tests compared with LIT-only patients, LIT with H. pylori , LIT and H. pylori with HIT, LIT and H. pylori with FM showed significantly higher exhaled H 2 levels (p=0.022). Pairwise comparison demonstrated H. pylori infected patients with LIT exhaled more H 2 compared to LIT-only (p=0.029). H. pylori with lactose- and histamine intolerance, and H. pylori with lactose-, histamine intolerance and FM compared to H. pylori -only patients indicated a significantly higher occurrence of stomach pain during lactose H 2 breath tests (p=0.012 and p=0.005, respectively). We demonstrate that LIT patients with high expiratory H 2 levels in lactose breath tests may have H. pylori infection and possibly additional food intolerance/malabsorption. Subsequently, besides H. pylori eradication, a dietician is necessary for an individually tailored reduction- or exclusion diet of symptom triggering food components., (Copyright © 2022 Schnedl et al.)

Hydrogen peroxide is a signal and effector molecule in the plant response to pathogen infection. Wheat resistance to Puccinia &nbsp; triticina Eriks. is associated with necrosis triggered by oxidative burst. We investigated which enzyme system dominated in host oxidative reaction to P. triticina infection. The susceptible Thatcher cultivar and isogenic lines with defined resistance genes were inoculated with P. triticina spores. Using diamine oxidase (DAO) and polyamine oxidase (PAO) inhibitors, accumulation of H 2 O 2 was analyzed in the infection sites. Both enzymes participated in the oxidative burst during compatible and incompatible interactions. Accumulation of H 2 O 2 in guard cells, i.e., the first phase of the response, depended on DAO and the role of PAO was negligible. During the second phase, the patterns of H 2 O 2 accumulation in the infection sites were more complex. Accumulation of H 2 O 2 during compatible interaction (Thatcher and Tc Lr34 line) moderately depended on DAO and the reaction of Tc Lr34 was stronger than that of Thatcher. Accumulation of H 2 O 2 during incompatible interaction of moderately resistant plants (Tc Lr24 , Tc Lr25 and Tc Lr29 ) was DAO-dependent in Tc Lr29 , while the changes in the remaining lines were not statistically significant. A strong oxidative burst in resistant plants (Tc Lr9 , Tc Lr19 , Tc Lr26 ) was associated with both enzymes' activities in Tc Lr9 and only with DAO in Tc Lr19 and Tc Lr26 . The results are discussed in relation to other host oxidative systems, necrosis, and resistance level.

Background/aim: Surgical stress significantly decreases serum diamine oxidase (DAO), a marker of intestinal mucosal maturation and integrity. This study aimed to determine the effects of postoperative enteral and total parenteral nutrition (EN and TPN, respectively) in patients with esophageal cancer., Patients and Methods: This prospective randomized trial compared serum DAO activities, nutritional states, trace elements and complications between patients who underwent esophagectomy and received EN or TPN for seven days thereafter., Results: Fifty-one patients were randomized to receive EN or TPN. The rates of change in serum DAO activity from the day before surgery were 0.79, 0.89 and 0.91 on postoperative days (POD) 1, 3 and 7, respectively, in the EN group, and 0.64, 0.76 and 1.06, respectively, in the TPN group, with no significant differences. Furthermore, the rates of changes in indicators of nutritional status, namely total protein, albumin, total cholesterol, trace element concentrations and infectious and non-infectious complications did not significantly differ between the groups., Conclusion: EN and/or TPN can be administered for early nutritional management until resumption of oral intake after esophagectomy according to the postoperative status of individual patients with esophageal cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The number of mast cells in various organs is elevated manifold in individuals with systemic mastocytosis. Degranulation can lead to life-threatening symptomatology. No data about the alterations of the metabolome and lipidome during an attack have been published., Objective: Our aim was to analyze changes in metabolomics and lipidomics during the acute phase of a severe mast cell activation event., Methods: A total of 43 metabolites and 11 lipid classes comprising 200 subvariants from multiple plasma samples in duplicate, covering 72 hours of a severe mast cell activation attack with nausea and vomiting, were compared with 2 baseline samples by using quantitative liquid chromatography-mass spectrometry., Results: A strong enterocyte dysfunction reflected in an almost 20-fold reduction in the functional small bowel length was extrapolated from strongly reduced ornithine and citrulline concentrations and was very likely secondary to severe endothelial cell dysfunction with hypoperfusion and extensive vascular leakage. Highly increased histamine and lactate concentrations accompanied the peak in clinical symptoms. Elevated asymmetric and symmetric dimethylarginine levels combined with reduced arginine levels compromised endothelial nitric oxide synthase activity and nitric oxide signaling. Specific and extensive depletion of many lysophosphatidylcholine variants indicates localized autotaxin activation and lysophosphatidic acid release. A strong correlation of clinical parameters with histamine concentrations and symptom reduction after 100-fold elevated plasma diamine oxidase concentrations implies that histamine is the key driver of the acute phase., Conclusions: Rapid elimination of elevated histamine concentrations through use of recombinant human diamine oxidase, supplementation of lysophosphatidylcholine for immunomodulation, inhibition of autotaxin activity, and/or blockade of lysophosphatidic acid receptors might represent new treatment options for life-threatening mast cell activation events., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

A putative diamine oxidase (DAO) from Yarrowia lipolytica PO1f (DAO-1) was homologously recombinantly integrated into the genome of Y. lipolytica PO1f using the CRISPR-Cas9 system for the subsequent DAO production in a bioreactor. Thereby, it was proven that the DAO-1 produced was indeed a functional DAO. The cultivation yielded 2343 ± 98 nkat/L culture with a specific DAO activity of 1301 ± 54.2 nkat/g protein , which was a 93-fold increase of specific DAO activity compared to the native Y. lipolytica PO1f DAO-1 production. The DAO-1 showed a broad substrate selectivity with tyramine, histamine, putrescine and cadaverine being the most favored substrates. It was most active at 40 °C, pH 7.2 in Tris-HCl buffer (50 mM) (with histamine as substrate), which is comparable to human and porcine DAOs. The affinity of DAO-1 towards histamine was lower compared to mammalian DAOs (K m = 2.3 ± 0.2 mM). Nevertheless, DAO-1 degraded around 75% of the histamine used in a bioconversion experiment with a food-relevant concentration of 150 mg/L. With its broad selectivity for the most relevant biogenic amines in foods, DAO-1 from Y. lipolytica PO1f is an interesting enzyme for application in the food industry for the degradation of biogenic amines., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study is being performed to evaluate the effectiveness and safety of TJ-100 TSUMURA Daikenchuto (DKT) Extract Granules in preventing post-hepatectomy digestive symptoms, and to examine the effects of DKT on small intestinal mucosal atrophy using diamine oxidase (DAO) and glucagon-like peptide-2 (GLP-2) activities. This is a randomized, open, controlled trial using patients treated with usual care as the control group. Patients who meet the inclusion criteria are randomized to the study groups. Eligible patients are randomized to the DKT therapy group (DKT administration for 14 days postoperatively or until the day of discharge if a patient leaves the hospital less than 14 days after the surgery) or the usual care group (no administration of DKT (ratio 1:1). Using the NRS (numeric rating scale) as an indicator, we will attempt to show whether DKT is effective for abdominal pain and bloating after surgery by comparing both groups. We will also attempt to evaluate postoperative small intestinal mucosal atrophy using DAO and GLP-2 activities in the serum, and postoperative nutrient absorption using nutrient assessment indicators. This study is being conducted according to the CONSORT statement. A consent form was signed by all participants, and the study protocol has been approved by the Central Review Board and Local Ethics Committee (CRB7180001).

Adverse reactions to food or food ingredients are more often perceived than objectively verifiable. However, reliable laboratory tests are often lacking. As a result, people with perceived adverse reactions to food often follow extensive elimination diets for years and unnecessarily restrict their diet, as in the case of the frequently suspected histamine intolerance. In this condition, laboratory parameters such as the determination of diamine oxidase in serum have been shown to be inconclusive. The lack of symptom reproducibility calls into question the clinical picture of adverse reactions to ingested histamine. In order to approach persons with perceived histamine intolerance and to support them in moving from blanket restrictions, which are often unnecessarily strict, to effective personalized therapeutic strategies, the present guideline of the Working Group on Food Allergy of the German Society of Allergology and Clinical Immunology (DGAKI) in cooperation with the Medical Association of German Allergists (AeDA), the Pediatric Allergology and Environmental Medicine (GPA) as well as the Swiss Society of Allergology and Immunology (SGAI) and the Austrian Society of Allergology and Immunology (ÖGAI) recommends a practicable diagnostic and therapeutic approach., (© Dustri-Verlag Dr. K. Feistle.)

Background: Excessive plasma histamine concentrations cause symptoms in mast cell activation syndrome, mastocytosis, or anaphylaxis. Anti-histamines are often insufficiently efficacious. Human diamine oxidase (hDAO) can rapidly degrade histamine and therefore represents a promising new treatment strategy for conditions with pathological histamine concentrations., Methods: Positively charged amino acids of the heparin-binding motif of hDAO were replaced with polar serine or threonine residues. Binding to heparin and heparan sulfate, cellular internalization and clearance in rodents were examined., Results: Recombinant hDAO is rapidly cleared from the circulation in rats and mice. After mutation of the heparin-binding motif, binding to heparin and heparan sulfate was strongly reduced. The double mutant rhDAO-R568S/R571T showed minimal cellular uptake. The short α-distribution half-life of the wildtype protein was eliminated, and the clearance was significantly reduced in rodents., Conclusions: The successful decrease in plasma clearance of rhDAO by mutations of the heparin-binding motif with unchanged histamine-degrading activity represents the first step towards the development of rhDAO as a first-in-class biopharmaceutical to effectively treat diseases characterized by excessive histamine concentrations in plasma and tissues., Funding: Austrian Science Fund (FWF) Hertha Firnberg program grant T1135 (EG); Sigrid Juselius Foundation, Medicinska Understödsförening Liv och Hälsa rft (TAS and SeV)., Competing Interests: EG, KT, KP, MS, SV, SV, GK, JP, TS, NB, TB is named as an inventor with The Medical University of Vienna and the University of Natural Resources and Life Sciences of a patent describing the rhDAO heparin-binding motif mutants presented herein (patent pending WO2020169577A1), KS none, MR None, BJ is named as an inventor with The Medical University of Vienna and the University of Natural Resources and Life Sciences of a patent describing the rhDAO heparin-binding motif mutants presented herein (patent pending WO2020169577A1)., (© 2021, Gludovacz et al.)

The intake of food may be an initiator of adverse reactions. Food intolerance is an abnormal non-immunological response of the organism to the ingestion of food or its components in a dosage normally tolerated. Despite the fact that food intolerance is spread throughout the world, its diagnosing is still difficult. Histamine intolerance (HIT) is the term for that type of food intolerance which includes a set of undesirable reactions as a result of accumulated or ingested histamine. Manifestations may be caused by various pathophysiological mechanisms or a combination of them. The problem with a "diagnosis" of HIT is precisely the inconstancy and variety of the manifestations in the same individual following similar stimuli. The diagnosing of HIT therefore requires a complex time-demanding multidisciplinary approach, including the systematic elimination of disorders with a similar manifestation of symptoms. Among therapeutic approaches, the gold standard is a low-histamine diet. A good response to such a diet is considered to be confirmation of HIT. Alongside the dietary measures, DAO supplementation supporting the degradation of ingested histamine may be considered as subsidiary treatment for individuals with intestinal DAO deficiency. If antihistamines are indicated, the treatment should be conscious and time-limited, while 2nd or 3rd generation of H 1 antihistamines should take precedence.

Silicon (Si) is a ubiquitous element in soil with well-known beneficial effects under certain conditions, in several plant species, if supplied in available form for uptake. It may alleviate damage in various stress situations and may also promote growth when no obvious stressors are applied. Effects of Si are often linked to mitigation of oxidative stress, in particular to the induction of antioxidant defense mechanisms. In the work presented, the impact of silicon provision on pro-oxidant systems was investigated in cucumber. Plants of the F1 cultivar hybrid 'Joker' were grown under in vitro conditions in the absence of any applied external stressor. Silicon provision decreased H 2 O 2 content and lowered lipid peroxidation in the leaves of the treated plants. This was paralleled by declining polyamine oxidase (PAO) and diamine oxidase (DAO) activities. Several PAO as well as lipoxygenase (LOX) genes were coordinately downregulated in Si-treated plants. Unlike in similar systems studied earlier, the Si effect was not associated with an increased transcript level of gene coding for antioxidant enzymes. These results suggest an inhibitory effect of Si provision on pro-oxidant amine oxidases, which may decrease the level of reactive oxygen species by retarding their production. This extends the molecular mechanisms linked to silicon effects onto redox balance in plants.

Aim: To analyze the diamine oxidase (DAO), the main catabolic enzyme of histamine, degradation activity and its relation with symptoms of persistent allergic rhinitis., Methods: In this descriptive and analytical observational study, we collected DAO activity levels and the nasal peak inspiratory flow., Results: Enzymatic activity deficit in 108 patients was 46.3% (95% CI, 0.44 - 0.63), 33.33% in mild and 47.92% in moderate/severe rhinitis (p = 0.376). The nasal peak inspiratory flow in patients with a deficit in DAO activity was 76.30 ± 28.40 L/min compared to 93.62 ± 37.50 L/min in patients with normal enzymatic activity (p = 0.010)., Conclusions: It seems that the lower the catabolic activity of DAO, the lower the nasal peak inspiratory flow observed. Although DAO activity levels could be a severity biomarker in allergic rhinitis, a cause-effect association cannot be concluded. The enzyme could be another actor in the pathophysiology of allergic rhinitis., (© Dustri-Verlag Dr. K. Feistle.)

Histamine is a critical inflammatory mediator in allergic diseases. We showed in a previous work that neutrophils from allergic patients produce histamine in response to allergens to which the patients were sensitized. Here, we investigate the molecular mechanisms involved in this process using peripheral blood neutrophils. We challenged these cells in vitro with allergens and analyzed histamine release in the culture supernatants. We also explored the effect of common therapeutic drugs that ameliorate allergic symptoms, as well as allergen-specific immunotherapy. Additionally, we examined the expression of histidine decarboxylase and diamine oxidase, critical enzymes in the metabolism of histamine, under allergen challenge. We show that allergen-induced histamine release is dependent on the activation of the phosphoinositide 3-kinase, mitogen-activated protein kinase p38, and extracellular signal-regulated kinase 1/2 signaling pathways. We also found a contribution of the phosphatase calcineurin to lesser extent. Anti-histamines, glucocorticoids, anti-M3-muscarinic receptor antagonists, and mainly β 2 -receptor agonists abolished the allergen-dependent histamine release. Interestingly, allergen-specific immunotherapy canceled the histamine release through the downregulation of histidine decarboxylase expression. Our observations describe novel molecular mechanisms involved in the allergen-dependent histamine release by human neutrophils and provide new targets to inhibit histamine production., (© 2021 Federation of American Societies for Experimental Biology.)

Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract. Involvement of the GI mucosa in various disorders and diseases, several with unknown origin, and the effects of some medications seem to reduce gastrointestinal DAO activity. HIT causes variable, functional, nonspecific, non-allergic GI and extra-intestinal complaints. Usually, evaluation for HIT is not included in differential diagnoses of patients with unexplained, functional GI complaints or in the here-listed disorders and diseases. The clinical diagnosis of HIT is challenging, and the thorough anamnesis of all HIT-linked complaints, using a standardized questionnaire, is the mainstay of HIT diagnosis. So far, DAO values in serum have not been established to correlate with DAO activity in the gut, but the diagnosis of HIT may be supported with determination of a low serum DAO value. A targeted dietary intervention, consisting of a histamine-reduced diet and/or supplementation with oral DAO capsules, is helpful to reduce HIT-related symptoms. This manuscript will present why histamine should also be taken into account in the differential diagnoses of patients with various diseases and disorders of unknown origin, but with association to functional gastrointestinal complaints. In this review, we discuss currently increasing evidence that HIT is primarily a gastrointestinal disorder and that it originates in the gut.

Objective: To observe the effect of intermittent hypoxia on intestinal bacterial translocation and mesenteric lymph node (MLN) structure and explore its mechanism. Methods: Twenty-four adult male Wistar rats were randomly divided into an experimental group (HI group) and a control group (UC group), with 12 rats in each. During the experiment, both groups were fed under the same conditions, but the HI group received simulated sleep apnea with hypoxic treatment. On the last day of the 2nd and 4th week of the experiment, 20% urethane(0.7 ml/100g) was used for anesthesia, and MLNs and corresponding small intestinal tissues were aseptically collected.HE staining was used to observe the microscopic changes of the tissues. The lymph node tissue was sent for pathogenic culture. The levels of oxide dismutase (SOD), lipid peroxide (MDA) and reactive oxygen species (ROS) were measured for the extent of oxidative stress. Serum diamine oxidase (DAO) was measured to assess the extent of intestinal mucosal damage. Result: MLNs and their corresponding small intestines were damaged in the HI group as compared to the UC group. With the prolongation of intermittent hypoxic time, the number of germinal centers in MLNs was significantly reduced, with the volume reduced, cortical medullary fusion aggravated, and the area ratio increased. The intestinal tissue showed severe damage to the intestinal epithelium, increased permeability, mucosal edema, and changes of the crypts. At the 4th week, MLNs in the HI group grew Clostridium perfringens under anaerobic conditions, confirming intestinal bacterial translocation. The contents of ROS, SOD and MDA in MLNs of the HI group were significantly higher than those in the UC group ( P <0.05). At the 2nd week and the 4th week, the contents of ROS, SOD and MDA were not significantly changed in the UC group( P >0.05). While the content of ROS and MDA in MLNs of the HI group at 4th week was significantly higher than that in the second week ( P <0.05), but no change of SOD was observed ( P >0.05). Serum DAO levels in the HI group were higher than those in the UC group at week 2 and week 4 ( P <0.05), suggesting that the degree of intestinal mucosal injury in the HI group was more serious than that in the UC group. Conclusion: Hypoxic exposure aggravated the degree of oxidative stress in rats. With the prolongation of intermittent hypoxia, the intestinal mucosa of rats was seriously damaged. The intestinal flora shifted to damage the structure of mesenteric lymph nodes, and oxidative stress was further aggravated, which in turn affected the integrity of the intestinal autoimmune function.

In westernized countries, adverse reactions to ingested foods are reported to affect up to 20% of the population. Functional, nonspecific, non-allergic gastrointestinal complaints are mainly due to the intolerance/malabsorption of carbohydrates (lactose and fructose), proteins (gluten), and biogenic amines (histamine). Food intolerance/malabsorption is defined by one or several of the above mentioned food components not being degraded and/or absorbed properly within the gastrointestinal tract. Food intolerance/malabsorption causes variable, functional, nonspecific, non-allergic gastrointestinal and extra-intestinal complaints, and a detailed diagnostic workup for all possible etiologic factors in individual patients is essential. Usually, evaluation for histamine intolerance is not included in differential diagnoses of patients with functional, nonspecific, non-allergic gastrointestinal complaints. A targeted dietary intervention for single or possibly combined intolerance/malabsorption is required. In this article, we review currently discussed differential diagnoses and available tests for intolerance/malabsorption. Accordingly, we aim to outline why including histamine and, histamine intolerance, should be considered in differential diagnoses of patients with functional, nonspecific, non-allergic gastrointestinal complaints.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H 2 ) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H 2 ) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal-Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption ( p < 0.004 and p < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H 2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal-Wallis test AUCs demonstrated a significant difference between all three groups ( p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H 2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.