Search

Histamine intolerance is associated with impaired histamine metabolism due to diamine-oxidase (DAO) enzyme deficiency at intestinal level. The recommended strategy to alleviate the symptomatology is a low-histamine diet supplemented with DAO. Different sources of DAO enzyme have been characterized in the literature (animal, vegetal and microbial), although only the porcine kidney protein extract has been approved as food supplement. Despite optimistic clinical results of DAO supplementation, variability in enzymatic activity of this type of active ingredient is reported, potentially linked to manufacturing processes. The aim of this work was to evaluate the impact of the raw material and the technological process of obtaining the porcine kidney protein extract on DAO activity, and its evolution during storage at room temperature (25 °C) and refrigeration (4 °C). Twenty batches of DAO-containing extract were analyzed and found to have a consistent histamine-degrading activity. The powder extract was prepared by mincing and homogenizing porcine kidneys, defatting with acetone, and drying at 40 °C for 6 h. The inclusion of a biocidal step before acetone extraction was evaluated on DAO activity. The use of sodium hypochlorite and irradiation (8kGy) did not have a negative impact on DAO activity. Moreover, the inclusion of an initial freeze-drying step of the raw material yielded an extract with higher DAO activity. On the other hand, the effect of applying higher temperatures (70 °C, 80 °C, and 90 °C) during the extract drying process for 3 and 6 h was evaluated, reporting a significant decrease of the enzymatic activity, with losses of 10–20 % for every 10 °C increase in temperature. Refrigeration was the only storage method capable of preserving enzymatic activity for at least 24 months. The manufacturing and storage of porcine kidney extract are crucial steps in the formulation of DAO supplements suitable for the treatment of histamine intolerance.

Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body's capacity to eliminate it. Researchers have attributed several reasons to this condition, such as genetic factors, alcohol, and dietary deficiencies, among other elements. Symptoms of histamine intolerance have been found to extend beyond the gastrointestinal tract and to the whole body, with these symptoms being sporadic and non-specific. This review will explore various aspects related to histamine intolerance, such as its causes, symptoms, diagnosis, and information related to management. [ABSTRACT FROM AUTHOR]

A retrospective pilot study was carried out to investigate the prevalence of four variants of the diamine oxidase (DAO) encoding gene (AOC1) in Caucasian adults with symptoms of histamine intolerance. In a cohort of 100 patients and 100 healthy individuals, DAO-encoding gene non-synonymous Single Nucleotide Variations (SNVs) were genotyped by multiplex single-nucleotide primer extension (SNPE) and capillary electrophoresis, and serum DAO activity was analyzed with a radio-extraction assay. The study found that 79% of individuals with symptoms of histamine intolerance harbored one or more of the four SNVs associated with reduced DAO activity. No significant differences were found in the prevalence of any variant between the group of patients and healthy controls. However, when considering the status of the alleles associated with DAO deficiency, more homozygous alleles were observed in histamine-intolerant patients. Moreover, a slightly but statistically higher percentage of patients had a high genetic risk score, reflecting the cumulative effect of carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous). A relationship between serum DAO activity and the genetic load of one specific SNV was observed, with DAO activity being significantly lower in patients homozygous for rs2052129. These results potentially support that carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous) is more relevant than the mere presence of one or more SNVs. Further studies are needed to determine the predictive value of these DAO-encoding gene variants. [ABSTRACT FROM AUTHOR]

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier. [ABSTRACT FROM AUTHOR]

Metabolic adaptation to cold stress plays an important role in the growth, survival, and yield of crops. Diamine cadaverine (Cad) as an osmolyte may take part in counteracting the oxidative stress induced by cold stress in chickpea. In this experiment, content of hydrogen peroxide (H2O2), Cad, activity of diamine oxidase (DAO), and its relative gene expression (DAO) in cold-tolerant (Sel96th11439) and cold-sensitive (ILC533) chickpea (Cicer arietinum L.) genotypes under cold stress (4°C) as a factorial experiment in a completely randomized design (CRD) were studied. In tolerant genotype H2O2 content after a significant increase on the first day of cold stress decreased significantly on the sixth day of cold stress compared to control condition (up to 4.7%), while, its accumulation was observed in sensitive genotype (up to 50%). These results indicated a relative acclimation to cold stress in tolerant genotype. The Cad metabolite content (18 nmol/g FW) was observed under cold stress in tolerant genotype on the sixth day of stress. Under cold stress, in tolerant genotype increasing Cad content was accompanied with an increase in DAO activity and relative expression of DAO gene as biosynthetic pathways of this metabolite (up to 3.5- and 3-fold, respectively). The maximum activity of this route was observed in tolerant genotype on the sixth day of cold stress. In the late responses under cold stress, the accumulation of Cad in tolerant genotype led to reduced cell damage (H2O2 results) and improved cold tolerance. These indices were useful in assessment of chickpea genotypes under cold stress and breeding programs. [ABSTRACT FROM AUTHOR]

A retrospective pilot study was carried out to investigate the prevalence of four variants of the diamine oxidase (DAO) encoding gene (AOC1) in Caucasian adults with symptoms of histamine intolerance. In a cohort of 100 patients and 100 healthy individuals, DAO-encoding gene non-synonymous Single Nucleotide Variations (SNVs) were genotyped by multiplex single-nucleotide primer extension (SNPE) and capillary electrophoresis, and serum DAO activity was analyzed with a radio-extraction assay. The study found that 79% of individuals with symptoms of histamine intolerance harbored one or more of the four SNVs associated with reduced DAO activity. No significant differences were found in the prevalence of any variant between the group of patients and healthy controls. However, when considering the status of the alleles associated with DAO deficiency, more homozygous alleles were observed in histamine-intolerant patients. Moreover, a slightly but statistically higher percentage of patients had a high genetic risk score, reflecting the cumulative effect of carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous). A relationship between serum DAO activity and the genetic load of one specific SNV was observed, with DAO activity being significantly lower in patients homozygous for rs2052129. These results potentially support that carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous) is more relevant than the mere presence of one or more SNVs. Further studies are needed to determine the predictive value of these DAO-encoding gene variants.

Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body’s capacity to eliminate it. Researchers have attributed several reasons to this condition, such as genetic factors, alcohol, and dietary deficiencies, among other elements. Symptoms of histamine intolerance have been found to extend beyond the gastrointestinal tract and to the whole body, with these symptoms being sporadic and non-specific. This review will explore various aspects related to histamine intolerance, such as its causes, symptoms, diagnosis, and information related to management.

Efforts are currently being directed to identify a non-invasive marker that can serve as a solid and clinically irrefutable diagnostic criterion for histamine intolerance associated with diamine oxidase (DAO) deficiency. Accordingly, the identification of biomarkers of histamine (HA) metabolism in urine is proposed as a possible new diagnostic strategy. It is hypothesized that individuals with histamine intolerance could have a different urinary profile of HA and its metabolites in comparison with the healthy population. Thus, the aim of this study was to assess the urinary excretion of HA and 1-methylhistamine (MHA) in individuals diagnosed with histamine intolerance and in a control group. Levels of HA and MHA were compared between 24 h and first morning spot urine in a subgroup of 14 control individuals. Then, HA and MHA concentrations in spot urine of 32 histamine intolerant and 55 control individuals were determined by ultra-high performance liquid chromatography and fluorometric detection (UHPLC-FL) and normalized by creatinine. No differences were found between HA and MHA levels in 24 h and first morning samples. Overall, histamine intolerant patients presented a distinct urinary excretion profile compared to the control group due to lower levels of MHA. No differences in urinary MHA were observed related to serum DAO activity. Spot urine samples were thus validated as a reliable tool to determine the urinary excretion of HA and MHA. These results constitute a starting point for the study of HA metabolomics as a suitable and non-invasive approach to histamine intolerance diagnosis.

Histamine intolerance (HIT) is food intolerance of non-immunological origin, and it results from an imbalance between the consumption of histamine with food and the organism ability to metabolize it. The patients with HIT were found to have a significantly reduced concentration of histamine-degrading enzymes, diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). Factors which have been identified that are conducive to histamine intolerance are: genetic factors, dysbacteriosis, chronic diseases – especially allergic and intestinal diseases, chronic infections, mastocytosis and some drug use. Clinical symptoms of histamine excess may affect various organs and systems - the most common are skin symptoms (pruritis, erythema) nausea, vomiting, abdominal pain, diarrhea, headaches and sometimes severe reactions with shortness of breath, arrhythmias, blood pressure drop, and even cardiac arrest. Diagnostic methods in HIT utilize determination of serum DAO, determination of histamine metabolites in urine, measurement of the histamine wheal in the 50th minute of the skin prick test (SPT), gastroscopy with intestinal biopsy, diagnostic and therapeutic test, oral histamine-challenge test and genetic tests. The mainstay of histamine intolerance treatment if a low-histamine diet. Patients should avoid products belonging to the three groups of food: containing large amounts of histamine, histamine liberators, and products inhibiting the activity of DAO. Additionally, supplements containing DAO and antihistamines can be used.

Histamine intolerance (HIT) is food intolerance of non-immunological origin, and it results from an imbalance between the consumption of histamine with food and the organism ability to metabolize it. The patients with HIT were found to have a significantly reduced concentration of histamine-degrading enzymes, diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). Factors which have been identifi ed that are conducive to histamine intolerance are: genetic factors, dysbacteriosis, chronic diseases -- especially allergic and intestinal diseases, chronic infections, mastocytosis and some drug use. Clinical symptoms of histamine excess may affect various organs and systems - the most common are skin symptoms (pruritis, erythema) nausea, vomiting, abdominal pain, diarrhea, headaches and sometimes severe reactions with shortness of breath, arrhythmias, blood pressure drop, and even cardiac arrest. Diagnostic methods in HIT utilize determination of serum DAO, determination of histamine metabolites in urine, measurement of the histamine wheal in the 50th minute of the skin prick test (SPT), gastroscopy with intestinal biopsy, diagnostic and therapeutic test, oral histamine-challenge test and genetic tests. The mainstay of histamine intolerance treatment if a low-histamine diet. Patients should avoid products belonging to the three groups of food: containing large amounts of histamine, histamine liberators, and products inhibiting the activity of DAO. Additionally, supplements containing DAO and antihistamines can be used. [ABSTRACT FROM AUTHOR]

Histamine intolerance (HIT) is a common disorder associated with impaired histamine metabolism. Notwithstanding, it is often misdiagnosed as other diseases because of its lack of specific clinical manifestations. HIT did not gain traction until the early 21st century. In this review, we will focus on the latest research and elaborate on the clinical manifestations of HIT, including its manifestations in special populations such as atopic dermatitis (AD) and chronic urticaria (CU), as well as the latest understanding of its etiology and pathogenesis. In addition, we will explore the latest treatment strategies for HIT and the treatment of specific cases. [ABSTRACT FROM AUTHOR]

Nowadays, certain uncertainties related to the onset of histamine adverse effects remain unsolved and still require further research. Questions still to be resolved include the wide range of doses at which dietary histamine may trigger symptoms of intoxication (100–10,000 mg/kg) or the appearance of symptoms of histamine intolerance after the consumption of foods presumable without histamine. It seems feasible that other amines, by acting as competitive substrates, could interfere with histamine degradation by the intestinal enzyme diamine oxidase (DAO). Therefore, the aim of this study was to elucidate the interference of different amines on the rate of histamine degradation by DAO. A series of in vitro enzymatic assays were performed using histamine as the reaction substrate combined with different proportions of putrescine, cadaverine, tyramine, spermidine, and spermine (1:0.25, 1:1, 1:4, 1:20). Putrescine and cadaverine significantly delayed histamine degradation at all tested concentrations (p < 0.001). The greatest effect was observed when putrescine or cadaverine concentrations were 20-fold higher than that of histamine, its degradation being reduced by 70 and 80%, respectively, compared to histamine alone (28.16 ± 1.0 mU). In contrast, tyramine, spermidine and spermine significantly inhibited the histamine degradation rate only at the highest concentration (1:20), reducing it by 32–45%. These results demonstrate that other biogenic amines interfere with histamine metabolization by DAO in vitro, the extent depending on the substrate. These findings could explain why susceptibility to dietary histamine is so variable and account for the discrepancies in the scientific databases regarding the amount of histamine that triggers adverse health effects.

Objective Metabolic adaptation to cold stress plays an important role in the growth, survival and yield of crops. Gamma aminobutyric acid (GABA) as an osmolyte may take part in counteracting the oxidative stress induced by cold stress in chickpea. Material and methods In this experiment, content of Putrescine (Put),GABA, Hydrogen Peroxide (H2O2), activity of Diamine Oxidase (DAO) andrelative expression ofGlutamate Gecarboxylase1 (GAD1)gene in cold-tolerant (Sel96th11439) and cold-sensitive (ILC533) chickpea (Cicer arietinum L.) genotypes under cold stress (4°C)as a factorial experiment in a Completely Randomized Designwere studied. Results In tolerant genotype H2O2 content after a significant increase on the first day of cold stress decreased significantly on the sixth day of cold stress compared to control conditions (up to 4.7%) while its accumulation was observed in sensitive genotype (up to 50%). These results indicated a relative acclimation to cold stress in tolerant genotype. Under cold stress, GABA and Put contents in tolerant genotype was higher compared to sensitive genotype (up to 14% and 35%, respectively). Under cold stress, in tolerant genotype increasing GABA content was accompanied with an increase in DAO activity and relative expression of GAD1 gene as biosynthetic pathways of this metabolite (up to 3- and 17-fold, respectively). The maximum activity of these two pathways was observed in tolerant genotype on the sixth day of cold stress. Conclusions Under cold stress, the accumulation of GABA in tolerant genotype led to reduced cell damage (H2O2 results) and improved cold tolerance. These indices were useful in assessment of chickpea genotypes under cold stress and breeding programs.

Histamine intolerance (HIT) is a common disorder associated with impaired histamine metabolism. Notwithstanding, it is often misdiagnosed as other diseases because of its lack of specific clinical manifestations. HIT did not gain traction until the early 21st century. In this review, we will focus on the latest research and elaborate on the clinical manifestations of HIT, including its manifestations in special populations such as atopic dermatitis (AD) and chronic urticaria (CU), as well as the latest understanding of its etiology and pathogenesis. In addition, we will explore the latest treatment strategies for HIT and the treatment of specific cases.

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier., Materials and Methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0., Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations., Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier., Competing Interests: The 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 © 2024 Cai, Gong, Xiang, Zhang and Pan.)

Histamine intolerance (HIT) is a non-immunological disorder associated with an impaired ability to metabolize ingested histamine. Manifestation of HIT includes gastrointestinal and non-gastrointestinal symptoms. Clinical symptoms of HIT are non-specific and can imitate different diseases such as allergies, food intolerance, mastocytosis and other. The diagnosis of HIT is difficult. There are several candidate tests to detect DAO insufficiency, but their informative value is questionable. Currently, a positive clinical effect of a low-histamine diet is the most important for establishing the diagnosis. Equally in the treatment, a low-histamine diet is the most crucial approach. Other therapeutic options such as DAO supplementation treatment with antihistamines or probiotics are considered as complementary treatments. Our article provides a review on histamine intolerance, focusing on etiology and the diagnostic and treatment possibilities.

Summary Background & aims Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among histamine related symptoms, headache is one of the most recorded. Current clinical strategies for the treatment of the symptomatology related to this disorder are based on the exclusion of foods with histamine or other bioactive amines and/or exogenous DAO supplementation. The aim of this study was to assess the efficacy of a food supplement consisting of DAO enzyme as a preventive treatment of migraine in patients with DAO deficiency through a randomized double-blind trial. Methods 100 patients with confirmed episodic migraine according to current International Headache Society (IHS) criteria and DAO deficiency (levels below 80 HDU/ml) were randomized in two groups. One group received DAO enzyme supplementation and the other received placebo for one month. Clinical outcomes assessed were duration and number of attacks, perception of pain intensity and adverse effects during treatment. The use of triptans was also recorded. Results Great variability was found in the duration of migraine attacks reported by placebo and DAO groups. A significant reduction (p = 0.0217) in hours of pain was achieved in patients treated with DAO supplement, with mean durations of 6.14 (±3.06) and 4.76 (±2.68) hours before and after treatment, respectively. A smaller reduction without statistical signification was also observed for this outcome in the placebo group, from 7.53 (±4.24) to 6.68 (±4.42) hours. Only in DAO group, a decrease in the percentage of patients taking triptans was observed. The number of attacks and the scores of pain intensity showed a similar reduction in both groups. No adverse effects were registered in patients treated with DAO enzyme. Conclusions Migrainous patients supplemented with DAO enzyme during one month significantly reduced the duration of their migraine attacks by 1.4 h. No statistically significant reduction was found in placebo group before and after treatment. The reduction of pain hours observed in placebo group (0.9 h) could explain the lack of significant differences between both study groups. One month of DAO supplementation has demonstrated a positive trend in the improvement of migraine but more studies with a longer treatment period are needed to better assess the efficacy of DAO supplementation. Clinical trial registration number ISRCTN10091019; www.isrctn.org. [ABSTRACT FROM AUTHOR]

Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine.

Histamine intolerance is a disorder in the homeostasis of histamine due to a reduced intestinal degradation of this amine, mainly caused by a deficiency in the enzyme diamine oxidase (DAO). Among the several multi-faced symptoms associated with histamine intolerance, headache is one of the most recognized and disabling consequences. The aim of this study was to determine the prevalence of DAO deficiency in patients with a confirmed migraine diagnosis according to the current International Headache Society (IHS) and in non-migraine subjects. DAO activity was assessed in a total of 198 volunteers recruited at the Headache Unit of the Hospital General de Catalunya, 137 in the migraine group and 61 as a control group. DAO enzyme activity in blood samples was determined by ELISA test. Values below 80 HDU/ml (Histamine Degrading Unit/ml) were considered as DAO deficient. Mean value of DAO activity from migraine population (64.5 ± 33.5 HDU/ml) was significantly lower (p < 0.0001) than that obtained from healthy volunteers (91.9 ± 44.3 HDU/ml). DAO deficiency was more prevalent in migraine patients than in the control group. A high incidence rate of DAO deficiency (87%) was observed in the group of patients with migraine. On the other hand, 44% of non-migranous subjects had levels of DAO activity lower than 80 HDU/ml. Despite the multifactorial aetiology of migraine, these results seem to indicate that this enzymatic deficit could be related to the onset of migraine. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Lycium barbarum and Astragalus membranaceus are two traditional medicinal herbs widely used in China for nourishing Yin and reinforcing Qi. The purpose of the study was to investigate the prophylactic and curative effects of crude polysaccharides (QHPS) extracted from a two-herb formula composed of Lycium barbarum and Astragalus membranaceus at a ratio of 2:3 in colitis rats, and to further elucidate the potential mechanism of action in epithelial cell proliferation in vitro. Materials and methods: An acetic acid (AA)-induced ulcerative colitis rat model was applied in the study. Two independent protocols were used to assess the prophylactic and curative effects of QHPS, respectively, in which rats were either pre-treated with QHPS (0.18g/kg) for 14 days prior to AA induction, or post-treated with QHPS for 7 days after AA induction. The stool consistency and weight loss were used to evaluate disease activity. The morphological changes in intestinal mucosa at the end of the experiments were observed. The serum levels of endotoxin (EDT), diamine oxidase (DAO) and d-lactate (DLA), important biochemical markers for evaluating intestinal mucosal structure and function, were measured. In the in vitro mechanistic studies, rat intestinal epithelial cells (IEC-6) were used to access for epithelium regeneration. Results: The intra-colonic instillation of AA induced ulcerative colitis in rat, as indicated by diarrhea, weight loss, and colonic mucosal damage. Both prophylactic and curative treatments effectively reduced the weight loss and diarrhea and attenuated the colonic mucosal damage associated with inducible colitis. The significant increase in serum levels of DAO, DLA and EDT was induced by AA and inhibited by QHPS treatment. Moreover, QHPS could significantly stimulate IEC-6 proliferation in a dose-dependent manner (p<0.05). Conclusion: The present study indicated for the first time that polysaccharides extracted from this two-herb formula can protect against experimental ulcerative colitis, presumably by promoting the recovery of the intestinal barrier. [Copyright &y& Elsevier]

Highlights: [•] Article concerned the impact of aluminum on root nodules. [•] Determination of subcellular H2O2 and DAO localization in stressed pea nodules. [•] Consequence of increased content of stressors was the modification of nodule apoplast. [•] We noted increased accumulation of H2O2 and DAO activity in the Al-treated infection threads. [Copyright &y& Elsevier]

Grapes are economically the most important fruit worldwide. However, the complexity of biological events that lead to ripening of nonclimacteric fruits is not fully understood, particularly the role of polyamines' catabolism. The transcriptional and metabolic profilings complemented with biochemical data were studied during ripening of Trincadeira grapes submitted to guazatine treatment, a potent inhibitor of polyamine oxidase activity. The mRNA expression profiles of one time point (EL 38) corresponding to harvest stage was compared between mock and guazatine treatments using Affymetrix GrapeGen® genome array. A total of 2113 probesets (1880 unigenes) were differentially expressed between these samples. Quantitative RT-PCR validated microarrays results being carried out for EL 35 (véraison berries), EL 36 (ripe berries) and EL 38 (harvest stage berries). Metabolic profiling using HPLC and 1H NMR spectroscopy showed increase of putrescine, proline, threonine and 1-O-ethyl- β -glucoside in guazatine treated samples. Genes involved in amino acid, carbohydrate and water transport were down-regulated in guazatine treated samples suggesting that the strong dehydrated phenotype obtained in guazatine treated samples may be due to impaired transport mechanisms. Genes involved in terpenes' metabolism were differentially expressed between guazatine and mock treated samples. Altogether, results support an important role of polyamine catabolism in grape ripening namely in cell expansion and aroma development. [ABSTRACT FROM AUTHOR]

Abstract: The roles of proline and polyamines (PAs) in the drought stress responses of tobacco plants were investigated by comparing the responses to drought alone and drought in combination with heat in the upper and lower leaves and roots of wild-type tobacco plants and transformants that constitutively over-express a modified gene for the proline biosynthetic enzyme Δ1-pyrroline-5-carboxylate synthetase (P5CSF129A; EC 2.7.2.11/1.2.1.41). In both genotypes, drought stress coincided with a decrease in relative water content (RWC) that was much less severe in the upper leaves than elsewhere in the plant. The drought also increased proline levels in both genotypes. A brief period of heat stress (2 h at 40 °C) at the end of the drought period did not significantly influence the proline levels in the upper leaves and roots but caused a further increase in the lower leaves of both genotypes. The rate at which these elevated proline levels returned to normal during the post-stress recovery period was slower in the transformants and plants that had been subjected to the combined stress. In both genotypes, drought stress significantly reduced the levels of spermidine (Spd) and putrescine (Put) in the leaves and roots relative to those for controls, and increased the levels of spermine (Spm) and diaminopropane (Dap, formed by the oxidative deamination of Spd and Spm). Spd levels may have declined due to its consumption in Spm biosynthesis and/or oxidation by polyamine oxidase (PAO; EC 1.5.3.11) to form Dap, which became more abundant during drought stress. During the rewatering period, the plants' Put and Spd levels recovered quickly and the activity of the PA biosynthesis enzymes in their leaves and roots increased substantially; this increase was more pronounced in transformants than WT plants. The high levels of Spm observed in drought stressed plants persisted even after the 24 h recovery and rewatering phase. The malondialdehyde (MDA) contents of the lower leaves of WTs increased substantially during the drought stress period; a less pronounced increase occurred in the transformants and after the application of the combined stress. After the post-stress recovery period, the MDA contents in the leaves of both genotypes were higher than those in the corresponding controls. The MDA contents of the upper leaves in plants of both genotypes remained relatively constant throughout, indicating that these leaves are preferentially protected against the adverse effects of oxidative stress and demonstrating the efficiency of the plants' induced antioxidative defense mechanisms. [Copyright &y& Elsevier]

Efforts are currently being directed to identify a non-invasive marker that can serve as a solid and clinically irrefutable diagnostic criterion for histamine intolerance associated with diamine oxidase (DAO) deficiency. Accordingly, the identification of biomarkers of histamine (HA) metabolism in urine is proposed as a possible new diagnostic strategy. It is hypothesized that individuals with histamine intolerance could have a different urinary profile of HA and its metabolites in comparison with the healthy population. Thus, the aim of this study was to assess the urinary excretion of HA and 1-methylhistamine (MHA) in individuals diagnosed with histamine intolerance and in a control group. Levels of HA and MHA were compared between 24 h and first morning spot urine in a subgroup of 14 control individuals. Then, HA and MHA concentrations in spot urine of 32 histamine intolerant and 55 control individuals were determined by ultra-high performance liquid chromatography and fluorometric detection (UHPLC-FL) and normalized by creatinine. No differences were found between HA and MHA levels in 24 h and first morning samples. Overall, histamine intolerant patients presented a distinct urinary excretion profile compared to the control group due to lower levels of MHA. No differences in urinary MHA were observed related to serum DAO activity. Spot urine samples were thus validated as a reliable tool to determine the urinary excretion of HA and MHA. These results constitute a starting point for the study of HA metabolomics as a suitable and non-invasive approach to histamine intolerance diagnosis., Competing Interests: The 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 © 2022 Sánchez-Pérez, Celorio-Sardà, Veciana-Nogués, Latorre-Moratalla, Comas-Basté and Vidal-Carou.)

Abstract: Nitrosative status has emerged as a key component in plant response to abiotic stress; however, knowledge on its regulation by different environmental conditions remains unclear. The current study focused on nitrosative responses in citrus plants exposed to various abiotic stresses, including continuous light, continuous dark, heat, cold, drought and salinity. Morphological observations and physiological analysis showed that abiotic stress treatments were sensed by citrus plants. Furthermore, it was revealed that nitrosative networks are activated by environmental stress factors in citrus leaves as evidenced by increased nitrite (NO) content along with the release of NO and superoxide anion (O2 −) in the vascular tissues. The expression of genes potentially involved in NO production, such as NR, AOX, NADHox, NADHde, PAO and DAO, was affected by the abiotic stress treatments demonstrating that NO-derived nitrosative responses could be regulated by various pathways. In addition, S-nitrosoglutathione reductase (GSNOR) and nitrate reductase (NR) gene expression and enzymatic activity displayed significant changes in response to adverse environmental conditions, particularly cold stress. Peroxynitrite (ONOO−) scavenging ability of citrus plants was elicited by continuous light, dark or drought but was suppressed by salinity. In contrast, nitration levels were elevated by salinity and suppressed by continuous light or dark. Finally, S-nitrosylation patterns were enhanced by heat, cold or drought but were suppressed by dark or salinity. These results suggest that the nitrosative response of citrus plants is differentially regulated depending on the stress type and underscore the importance of nitrosative status in plant stress physiology. [Copyright &y& Elsevier]

Abstract: Chronic eosinophilic bronchitis and bronchial hyperresponsiveness have been considered to be the fundamental features of bronchial asthma. However, the role of airway eosinophils in bronchial responsiveness in vivo has not been fully discussed. The aim of this study was to investigate the direct effect of airway eosinophil accumulation on bronchial responsiveness in vivo. Guinea pigs were transnasally treated with platelet activating factor (PAF) or vehicle twice a week for a total of 3 weeks. Anesthetized guinea pigs were surgically cannulated and artificially ventilated 48h after the last administration of PAF or vehicle. Ten minutes after the installation of artificial ventilation, ascending doses of histamine were inhaled. In a subsequent study, selective inhibitors of diamine oxidase and histamine N-methyltransferase were intravenously administered before the histamine inhalation in the PAF-treated animals. Next study was conducted 20min after treatment with indomethacin in this study line. Finally, ascending doses of methacholine were inhaled in our animal model. Proportion of eosinophils and the number of nuclear segmentation in bronchoalveolar lavage fluid significantly increased in guinea pigs treated with PAF compared with vehicle and this finding was confirmed histologically. Nevertheless, bronchial responsiveness to inhaled histamine, but not methacholine, was significantly decreased by the PAF treatment. This bronchoprotective effect induced by PAF remained following aminoguanidine and histamine N-methyltransferase administration, but abolished by treatment of indomethacin. These results suggest that in vivo airway eosinophils may reduce non-specific bronchial responsiveness through production of inhibitory or bronchoprotective prostanoids, but not through histaminase production. [Copyright &y& Elsevier]

Changes in cell viability, proliferation, cell and nuclear morphology including nuclear and DNA fragmentation induced by 0.05 and 1 mM CdSO4 (Cd2+) in tobacco BY-2 cell line (Nicotiana tabacum L.) were studied in the course of 7 days. Simultaneously changes in endogenous contents of both free and conjugated forms of polyamines (PAs) were investigated for 3 days. The application of 0.05 mM Cd2+ evoked decline of cell viability to approximately 60% during the first 24 h of treatment. Later on degradation of cytoplasmic strands, formation of the stress granules and vesicles, modifications in size and shape of the nuclei, including their fragmentation, were observed in the surviving cells. Their proliferation was blocked and cells elongated. Beginning the first day of treatment TUNEL-positive nuclei were detected in cells cultivated in medium containing 0.05 mM Cd2+. Treatment with highly toxic 1 mM Cd2+ induced fast decrease of cell viability (no viable cells remained after 6-h treatment) and cell death occurred before DNA cleavage might be initiated. The exposure of tobacco BY-2 cells to 0.05 mM Cd2+ resulted in a marked accumulation of total PAs (represented by the sum of free PAs and their perchloric acid (PCA)-soluble and PCA-insoluble conjugates) during 3-day treatment. The increase in total PA contents was primarily caused by the increase in putrescine (Put) concentration. The accumulation of free spermidine (Spd) and spermine (Spm) at 12 and 24 h in 0.05 mM Cd2+ treated BY-2 cells and high contents of Spd and especially Spm determined in dead cells after 1 mM Cd2+ application was observed. The participation of PA conjugation with hydroxycinnamic acids and PA oxidative deamination in maintaining of free PA levels in BY-2 cells under Cd2+-induced oxidative stress is discussed. [Copyright &y& Elsevier]

Many inhibitors of monoamine oxidase, particularly those developed during the past three decades, are often referred to as being “selective” for one or other isoform of the enzyme. However true this may be, selectivity within the EC 1.4.3.4 family does not preclude the possibility of interactions of these drugs with other proteins unrelated to monoamine oxidase. Indeed, evidence exists which either suggests or demonstrates directly that many of these inhibitors do interact with, and affect the behaviour of, other enzymes, receptor systems and uptake pumps, with potentially interesting consequences, desirable or otherwise, for the patient or the pharmacologist. An overview of many such interactions, and speculation upon some of the possible consequences, are provided in this review. [Copyright &y& Elsevier]

Besides its anticoagulant activity, the sulfated polysaccharide heparin has numerous other biological effects. Especially the antiinflammatory and immunoregulatory properties of heparin may be associated with its ability to release the histamine-degrading enzyme diamine oxidase (DAO) from tissue-bound sites into the circulation. Whereas DAO activity is at the limits of detection in normal human plasma, the application of heparin leads to a significant increase of plasma DAO activity. However, previously, only the effect of bolus injection of unfractionated heparin (UFH) had been studied. To investigate DAO release during continuous heparin infusion, 28 patients with deep vein thrombosis (DVT) undergoing heparin therapy were analyzed. Whereas continuous heparin infusion did not lead to any increase of plasma DAO activity in 12 patients (43%), 6 patients (21%) showed a single elevated and 10 patients (36%) permanently elevated plasma DAO activity. The groups of patients exhibiting different DAO release responses did not differ in age, sex, body weight, concomitant diseases, heparin infusion rates, coagulation indices, location and extension of thrombosis, or clinical outcome. However, the rate of idiopathic DVT was significantly higher in the group of patients releasing DAO. This study shows, for the first time, that continuous heparin infusion can lead to DAO release and that individuals exhibit considerable differences in their release response. Although the significance of heparin-induced DAO release needs further clarification, our results indicate that postheparin plasma DAO activity could be an interesting parameter correlated with idiopathic DVT. [Copyright &y& Elsevier]

Summary Although most work on polyamines in incompatible interactions between plants and pathogens has focussed on polyamines conjugated to phenolic compounds (hydroxycinnamic acid amides), changes in free polyamines and their catabolism have been shown to occur in such interactions. A common feature of these interactions is an increase in diamine oxidase (DAO) activity and, in some interactions, of polyamine oxidase (PAO). The activities of these two enzymes produces hydrogen peroxide (H2 O2 ), which may act in structural defense, as a signal molecule, or as an antimicrobial compound in host resistance. There are several possible roles for polyamines and polyamine catabolism in plant resistance to pathogen infection; H2 O2 produced might trigger the hypersensitive response (HR), thought to be a form of programmed cell death (PCD), the polyamine spermine might act as an inducer of PR proteins, and as a trigger for caspase activity and hence HR. There is, however, a need for more precise information on the timing and location of changes in polyamine metabolism in the development of resistance. Only with this information can a case be made for the involvement of polyamines and polyamine catabolism in plant defense. [ABSTRACT FROM AUTHOR]

The phytotoxic air pollutant ozone spontaneously generates reactive oxygen species (ROS) in the leaf apoplast, provokes hypersensitive response-like lesions and induces defence reactions that significantly overlap with pathogen and other oxidative stress responses. Consequently, ozone has been used as a tool to unravel in planta ROS-induced plant defence and cell death mechanisms. Ozone exposure stimulates an oxidative burst in leaves of sensitive plants, resulting in the generation and accumulation of hydrogen peroxide or superoxide anions in distinct species. Accumulation of these ROS precedes the induction of cell death, and both responses co-occur spatially in the periveinal regions of the leaves. The review summarizes some of the recent results that have been obtained concerning the molecular basis of apoplastic ROS production in monocot and dicot species. Signal molecules, in particular ethylene and salicylic acid, control and potentiate the oxidative burst and subsequent cell death in its initiation and propagation phases while jasmonate leads to lesion containment. Amplification mechanisms that result in the production of excess ROS and hypersensitive cell death are discussed as major factors in ozone sensitivity of plant species and cultivars. [Copyright &y& Elsevier]

Nowadays, certain uncertainties related to the onset of histamine adverse effects remain unsolved and still require further research. Questions still to be resolved include the wide range of doses at which dietary histamine may trigger symptoms of intoxication (100-10,000 mg/kg) or the appearance of symptoms of histamine intolerance after the consumption of foods presumable without histamine. It seems feasible that other amines, by acting as competitive substrates, could interfere with histamine degradation by the intestinal enzyme diamine oxidase (DAO). Therefore, the aim of this study was to elucidate the interference of different amines on the rate of histamine degradation by DAO. A series of in vitro enzymatic assays were performed using histamine as the reaction substrate combined with different proportions of putrescine, cadaverine, tyramine, spermidine, and spermine (1:0.25, 1:1, 1:4, 1:20). Putrescine and cadaverine significantly delayed histamine degradation at all tested concentrations ( p < 0.001). The greatest effect was observed when putrescine or cadaverine concentrations were 20-fold higher than that of histamine, its degradation being reduced by 70 and 80%, respectively, compared to histamine alone (28.16 ± 1.0 mU). In contrast, tyramine, spermidine and spermine significantly inhibited the histamine degradation rate only at the highest concentration (1:20), reducing it by 32-45%. These results demonstrate that other biogenic amines interfere with histamine metabolization by DAO in vitro , the extent depending on the substrate. These findings could explain why susceptibility to dietary histamine is so variable and account for the discrepancies in the scientific databases regarding the amount of histamine that triggers adverse health effects., Competing Interests: The 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 © 2022 Sánchez-Pérez, Comas-Basté, Costa-Catala, Iduriaga-Platero, Veciana-Nogués, Vidal-Carou and Latorre-Moratalla.)

Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine. [ABSTRACT FROM AUTHOR]

Bacterial translocation is believed to occur during cardiopulmonary bypass (CPB) because serum endotoxin concentrations rise. Intestinal ischemia during CPB, however, has never been proven directly. The condition of the intestinal mucosa during CPB was studied by measuring serum diamine oxidase (DAO) activity, an index of intestinal ischemia. Serum DAO activity, blood lactate concentration, and the arterial ketone body ratio (AKBR) were measured intraoperatively in four successive patients who underwent aortic arch replacement by the open distal anastomosis method. DAO activity rose after restoration of blood flow to the lower half of the body, and continued to rise throughout CPB. The lactate concentration also rose, mirroring the change in DAO activity, and returned to nearly normal 12 h after the operation. The AKBR decreased during CPB, with a mean minimum vale of 0.16 ± 0.07 immediately after the restoration of blood flow to the lower half of the body. The parallel rise in DAO activity and serum lactate concentration once blood flow to the lower half of the body was restored implies that ischemic injury to the mucosa of the small intestine occurs during CPB. The continued rise in these parameters throughout CPB is consistent with ongoing injury due to splanchnic hypoperfusion, as reflected in the decrease in the AKBR during the same period. [ABSTRACT FROM AUTHOR]

•  Change is reported in the biosynthetic and oxidative activity of hypersensitive (NN) and susceptible (nn) tobacco (Nicotiana tabacum) plants in response to tobacco mosaic virus (TMV). •  Mature leaves of nn and NN tobacco were collected over 0-72 h as uninoculated controls or after inoculation with TMV or phosphate buffer (mock-inoculation). The polyamine response to inoculation was analysed by measuring activity and gene expression of S-adenosylmethionine decarboxylase (SAMDC), arginine-(ADC) and ornithine decarboxylases (ODC); incorporation of labelled putrescine; and activity of diamine oxidase (DAO). •  In NN leaves SAMDC activity and transcript levels, and DAO activity increased in the TMV-inoculated plants but not in the other treatments; a two-fold increase in DAO activity was seen after 72 h. Both ADC and ODC activity increased in NN leaves at 72 h in TMV-inoculated plants; ADC mRNA increased with activity. The increase in SAMDC mRNA (24 h) preceded the rise in activity (72 h). [ 3 H]putrescine added to NN leaves led to enhanced label recovery and incorporation into spermidine and spermine in TMV-inoculated plants. No significant changes in biosynthetic or oxidative activity occurred in nn plants. •  After TMV inoculation, NN, unlike nn, tobacco plants upgrade polyamine synthesis and oxidation; this leads to changes in cellular components which might induce programmed cell death.