Changes In Histamine Levels Research Articles

Occurrence of Histamine in Commercial Cat Foods under Different Storage Conditions.

In fish-based foods, one of the effects of inappropriate storage can be the formation of biogenic amines. Among these, histamine is considered one of the most toxic. The purpose of the present study is to assess the occurrence of histamine in fish-based pet foods, and to evaluate the changes in histamine content during storage at different temperatures. For the analysis, an LC-MS/MS method was used. Fifty-eight pet foods were purchased, and an aliquot of them was analyzed just after opening the packages. Histamine was detected in 12 samples and concentrations ranged from 1.5 to 30.1 mg/kg. The remaining of each positive sample was divided into seven subsamples. One of them was used as a control sample and kept at −20 °C, while the other six were exposed to different environmental conditions. Samples exposed to room temperature showed no significant changes in histamine levels, while samples exposed to high temperatures showed significant increases in histamine content. Finally, samples exposed to refrigerator temperature showed a slight decrease in histamine levels. Under the experimental conditions, the EU limit of 100 mg/kg established for fishery products was never exceeded. These results seem to indicate a low risk of histamine intoxication in cats fed fish-based pet food.

Cryotherapy decreases histamine levels in the blood of patients with rheumatoid arthritis

Conventional physiotherapy (electrotherapy, magnetic fields), kinesitherapy, and whole-body cryotherapy (plus kinesitherapy) are used to relieve pain and inflammation or to improve function in rheumatic diseases. The aim of this study was to investigate the effects of different physiotherapies and cryotherapy on biochemical blood parameters of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Twenty patients with RA and 17 patients with OA received whole-body cryotherapy at -140 to -160 degrees C for 2 to 3 min, once daily for 4 weeks. The second group of patients (24 with RA and 28 with OA) received conventional physiotherapy for 4 weeks. We measured the parameters of neutrophil activation (respiratory burst, calprotectin) and markers of cartilage metabolism [N-acetyl-beta-D-hexosaminidase (NAHase), ectonucleotide pyrophosphohydrolase (NTPPHase)] twice: before and 3 months after cryotherapy or physiotherapy. We showed, for the first time, that cryotherapy significantly reduced (P < 0.001) histamine levels in the blood of patients with RA. The effect was long-lasting (for at least 3 months). The levels of blood histamine in patients with OA were not changed significantly. Cryotherapy also downregulated the respiratory burst of PMNs and NAHase activity and upregulated calprotectin levels and the activity of NTPPHase. However, these changes were not statistically significant. In contrast, there were no significant changes in histamine levels or the other biochemical parameters measured in groups of patients treated only with physiotherapy and kinesitherapy. It may be concluded that the beneficial clinical effects of cryotherapy in RA patients are in part due to the action on the production, release, or degradation of histamine.

Modifications of Inflammatory Pathways in Rat Intestine Following Chronic Ingestion of Depleted Uranium

The environmental contamination by dispersion of depleted uranium (DU) might result in its chronic ingestion of DU by local populations. The aim of this study was to determine if chronic ingestion of DU at low doses induces inflammatory reactions in intestine, first biological system exposed to uranium after ingestion. Experiments were performed with rats receiving uranium in drinking water (40 mg/l) during 3, 6, or 9 months. Several parameters referring to prostaglandin, histamine, cytokine, and nitric oxide (NO) pathways were assessed in ileum. Concerning the prostaglandin pathway, a twofold increase in gene expression of cyclooxygenase of type 2 was noted after 6 months, with no changes in prostaglandins levels. At the same time, a decrease in mast cell number was observed without any changes in histamine levels. Experiments on cytokines showed increased gene expression of interleukin (IL)-1beta and IL-10 at 6 months, and decreased messenger RNA level of CCL-2. This change was associated with decreased macrophage density. An opposite effect of DU was induced on neutrophils, since increased number was observed at 3 (x1.7) and 9 months (x3). The results obtained on NO pathway seemed to indicate that DU exposure inhibited this pathway (decreased endothelial NO synthase messenger RNA, inductive NO synthase activity and NO(2)(-)/NO(3)(-) levels) at 6 months. In conclusion, this study demonstrated that chronic ingestion of DU-induced time-dependent modifications of inflammatory pathways, notably in terms of immune cell content. The ultimate effects of DU contamination might be pathogenic by suppressing defense mechanisms or inducing hypersensitivity. Further experiments should be thus performed to determine real consequences on intestinal response to oral antigens.

Changes in the histaminergic system during vestibular compensation in the cat

To determine how the histaminergic system is implicated in vestibular compensation, we studied the changes in histidine decarboxylase (HDC; the enzyme synthesizing histamine) mRNA regulation in the tuberomammillary (TM) nuclei of cats killed 1 week, 3 weeks and 3 months after unilateral vestibular neurectomy (UVN). We also used one- and two-step bilateral vestibular neurectomized (BVN) cats to determine whether HDC mRNA regulation depended on the asymmetrical vestibular input received by the TM nuclei neurons. In addition, we analysed the HDC mRNA changes in the TM nuclei and the recovery of behavioural functions in UVN cats treated with thioperamide, a pure histaminergic drug. Finally, we quantified binding to histamine H3 receptors (H3Rs) in the medial vestibular nucleus (VN) by means of a histamine H3R agonist ([3H]N-alpha-methylhistamine) in order to further investigate the sites and mechanisms of action of histamine in this structure. This study shows that UVN increases HDC mRNA expression in the ipsilateral TM nucleus at 1 week. This increased expression persisted 3 weeks after UVN, and regained control values at 3 months. HDC mRNA expression was unchanged in the one-step BVN cats but showed mirror asymmetrical increases in the two-step BVN compared to the 1 week UVN cats. Three weeks' thioperamide treatment induced a bilateral HDC mRNA up-regulation in the UVN cats, which was higher than in the untreated UVN group. Binding to histamine H3Rs in the MVN showed a strong bilateral decrease after thioperamide treatment, while it was reduced ipsilaterally in the UVN cats. That such changes of the histaminergic system induced by vestibular lesion and treatment may play a functional role in vestibular compensation is strongly supported by the behavioural data. Indeed, spontaneous nystagmus, posture and locomotor balance were rapidly recovered in the UVN cats treated with thioperamide. These results demonstrate that changes in histamine levels are related to vestibular compensation.

Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep–wakefulness and prolonged wakefulness: An in vivo microdialysis study

Increased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/anterior hypothalamic area of cats during natural sleep–wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep. Samples were analyzed by a sensitive radioenzymatic assay. Mean basal levels of histamine in microdialysate during periods of wakefulness (1.155±0.225 pg/μl) did not vary during the 6 h of sleep deprivation. However, during the different sleep states, dramatic changes were observed in the extracellular histamine levels of preoptic/anterior hypothalamic area: wakefulness>non-rapid eye movement sleep>rapid eye movement sleep. Levels of histamine during rapid eye movement sleep were lowest (0.245±0.032 pg/μl), being significantly lower than levels during non-rapid eye movement sleep (0.395±0.081 pg/μl) and being only 21% of wakefulness levels. This pattern of preoptic/anterior hypothalamic area extracellular histamine levels across the sleep–wakefulness cycle closely resembles the reported single unit activity of histaminergic neurons. However, the invariance of histamine levels during sleep deprivation suggests that changes in histamine level do not relay information about sleep drive to the sleep-promoting neurons of the preoptic/anterior hypothalamic area.

Histamine is released in the wheal but not the flare following challenge of human skin in vivo: a microdialysis study.

The mediator mechanisms of the cutaneous wheal and flare response, which underlies allergic skin and urticarial conditions, are controversial. The wheal results primarily from a direct effect of histamine on the local vascular bed but to what extent does histamine diffuse within the wheal? The flare is neurogenic, in origin, being disseminated within the dermis by axon reflexes, but do the neuropeptides released from the nerve endings cause the vasodilatation directly or do they induce the further release of histamine which then transduces the flare? We have addressed these questions by inserting 216 microns diameter microdialysis fibres into the dermis within the different areas of the wheal and flare to monitor changes in histamine levels provoked by intradermal injections of histamine, allergen, codeine and substance P. Twenty-one subjects participated in the investigations. The histamine concentration in unprovoked skin was 10.5 +/- 0.6 nM. As the dialysis efficacy was approximately 50%, this equates to tissue concentrations of 20 nM. All provicants released large amounts of histamine at the injection site, maximum histamine levels being 337-1293 nM. Diffusion of histamine within the wheal was poor, levels at 2.3 mm and 3.7 mm from the site of injection being 4-22% and 0.2-3.7% respectively of those 1 mm from the injection site. No increased histamine levels were detected in the flare with any provicant. Atraumatic delivery to the skin of histamine in infusion concentrations of 30-10,000 nM caused concentration-related effects, at least 100 nM being necessary to induce a significant increase in skin blood flow, a threshold of 300-1000 being required to stimulate a visible flare and a measurable erythema, and 3000-10,000 nM being the minimum for induction of a wheal. Thus the skin blood vessels and nerves are responsive to histamine, but at relatively high concentrations. These data support the theory that the flare reaction to focal histamine injection or release is a neurogenic reflex not involving histamine release at its effector end.

The effect of methamphetamine on histamine level and histidine decarboxylase activity in the rat brain

To examine biochemical changes in the brain histamine (HA) neuron system after acute and chronic administrations of methamphetamine (MAP), HA levels and histidine decarboxylase (HDC) activities in the rat cortex, striatum, diencephalon, midbrain, pons-medulla and cerebellum were measured. In the cortex and striatum, acute administration of MAP (1 and 3 mg/kg) increased HA levels 1 h later. Acute administration of MAP (10 mg/kg) and chronic administration of MAP (3 mg/kg) for 21 days also increased HA levels and HDC activities in the cortex and striatum 1 h after the last injection. In the diencephalon, acute administration of MAP (3 and 10 mg/kg) and chronic administration of MAP (3 mg/kg) decreased HA level 1 h after the last injection, but chronic administration of MAP (3 mg/kg) increased HDC activity 1 h after the last injection. There were no significant changes in HA levels and HDC activities in other regions after acute and chronic administrations of MAP. These findings suggest that MAP may activate the brain HA neuron system, although MAP acts more strongly on the cortex and striatum than on the diencephalon.

Biogenic amines in silage

When analysing a series of laboratory silages made from orchardgrass, red clover and oats, the fluctuating dynamics of biogenic amines were observed. For levels of putrescine and cadaverine, a rapid exponential increase culminating approximately 30-50 days after ensiling is typical. A small decrease, reaching the minimum at approximately the 100th day, is sometimes followed by a second increase in amine concentrations achieving its maximum approximately 200-230 days after ensiling. Irregular curves of the dynamics probably originate in the simultaneous decarboxylation and deamination reactions along with other relevant amine degradation processes. The dynamics of other biogenic amines-spermidine, spermine and histamine are more difficult to predict. The changes in histamine levels resembled those in the diamines. Some 200 days after ensiling, considerable increases in this toxic amine were observed. The dynamics of some quality criteria, especially the degree of proteolysis, were in many cases similar to those of the amines.

Increase of albumin, eosinophil cationic protein, histamine, leukotrienes and mast cell tryptase in nasal lavage fluid after challenge with inhalant allergen extract

Allergic rhinitis patients underwent nasal challenge with allergen extract. Before and up to 10 h after nasal provocation, nasal lavage was performed every hour. In about one-third of the patients a biphasic influx of albumin was observed: an initial increase of albumin within 30 min after provocation and a 2nd peak 6–8 h after provocation. Allergen-induced changes in histamine levels were less pronounced than those of albumin, but with some patients biphasic responses were also seen. Increased leukotriene formation mainly occurred within one hour after allergen provocation.

Measurement of histamine in nasal lavage fluid: Comparison of a glass fiber-based fluorometric method with two radioimmunoassays

The determination of histamine in nasal secretions and nasal lavage fluid may be of importance to monitor activation of histamine containing cells in the nasal cavity. However, such studies have been besieged by controversy, specifically to findings of changes in histamine levels in relation to allergenic stimulation. This controversy may be due to the specificity and accuracy of the various methods used to determine histamine in the nasal fluid. We have therefore applied and compared three new methods to determine histamine in nasal lavage fluids obtained before and after allergen challenge in normal subjects and patients with allergic rhinitis. We used a fluorometric glass fiber-based histamine method (FHR) and two RIAs, I and II. The FHR (detection limit, 7.0 nmol) and the RIA II (detection limit, 0.2 nmol) are specific for histamine itself, whereas the RIA I (detection limit, 18.0 nmol) measures mainly methylhistamine and cross-reacts to some extent with histamine. The histamine levels in the nasal lavage fluids from the nasal challenges demonstrated histamine values between 100 and 2000 nmol/L of histamine with significantly higher levels in the postallergen challenges for the allergic subjects as compared to the normal control subjects. The FHR correlated well with the RIA I and RIA II methods with correlation coefficients of 0.77 to 0.88 (p less than 0.001), respectively. However, the RIA I (methylhistamine antibody) always demonstrated absolute histamine values 5% to 20% of values measured by the RIA II (at the level of cross-reactivity to histamine).(ABSTRACT TRUNCATED AT 250 WORDS)

An experimental model of death from anaphylactic shock with compound [formula omitted] and postmortem changes in levels of histamine in blood

The present study was made on an experimental animal model of a death from anaphylaxis, in which postmortem changes in levels of histamine and 1-methylhistamine, in whole blood were measured. Instead of the usual immunological method administering compound 48 80 , a degranulating agent of mast cell and the effect closely resembling the immuno-reaction, resulted in reliable death in a short time. The animals that died rapidly after the injection of compound 48 80 , were found to have large increases in levels of histamine and 1-methylhistamine soon after the administration. These results were similar to the results of injecting histamine exogenously. On the other hand, the animals that died after a longer time showed no increases in levels of those amines within about 24 h, but 24 hours after death histamine levels were only increased tremendously without rise in 1-MHA levels. These phenomena closely resembled those in the control animals that were treated with overdoses of Nembutal ®.

Vancomycin and the Red-Man Syndrome: Pharmacodynamics of Histamine Release

Two regimens for infusing vancomycin over 1 h (500 mg every 6 h for five doses or 100 mg every 12 h for three doses) were used in 11 volunteers. Subjects received both regimens one week apart; the regimen used first for each subject was randomized. Nine receiving the 1000-mg dose experienced the "red-man (neck)" syndrome; none had the reaction while receiving the 500-mg dose (P = .002). Plasma histamine concentration, measured every 10 min during the first infusion of each regimen, increased in most subjects given 1000-mg doses; there was only a slight change in histamine levels after 500-mg doses. There was a significant relation between histamine release and reaction severity; frequency and severity of the reaction declined with subsequent doses. We conclude that the red-man syndrome occurs frequently in normal adults who receive 1000 mg of vancomycin over 1 h, that vancomycin causes an infusion rate-dependent increase in plasma histamine concentration, and that the increase in plasma histamine concentration is correlated with the severity of the reaction.

Changes in Leucocyte Numbers without Diapedesis in Rats Given Platelet-Activating Factor (PAF-Acether)

Changes occurring in the blood and the peritoneal cavity following the intraperitoneal injection of platelet-activating factor (PAF-acether) into rats were compared with those when antigen was injected intraperitoneally into actively sensitised rats. A blood eosinophilia had been produced in the rats by an intravenous injection of Sephadex G200 6 days before either challenge. 5 min after PAF-acether, the total number of cells in the peritoneal washings had decreased and the concentration of extravasated dye-labelled plasma protein had increased with no change in histamine levels. On the other hand, antigen at this time produced nor only a decrease in cells and an increase in dye but also an increase in histamine concentration. Only antigen produced a cellular infiltration into the peritoneal cavity with an increase in numbers of neutrophils in the peritoneal washings at 4 h and of mononuclear cells and eosinophils at 24 h. In the blood at 4 h after either challenge, there was a neutrophilia and an eosinopenia. When PAF-acether and antigen were injected together into actively sensitised rats, leucocyte counts in the peritoneal washings increased by a similar amount, both at 4 and 24 h, as those in rats given antigen alone.

Histamine release and circulating cells after antigen inhalation in allergic dogs

Histamine can be recovered from the blood of ragweed-sensitized dogs after aerosol antigen challenge, although its source is unknown. Neutrophils and eosinophils have been recovered from bronchoalveolar lavage fluid (BALF) obtained under identical conditions. We investigated the time course of changes in histamine levels in plasma and BALF taken from ragweed-sensitized dogs after aerosol challenge. Changes in the numbers of circulating neutrophils, eosinophils, lymphocytes, monocytes, and platelets were also studied. After 3 min, total pulmonary resistance (RL) was maximally increased and systolic blood pressure was maximally decreased. Histamine levels in plasma and BALF were increased and circulating eosinophils and neutrophils were decreased. After 15 min, platelet numbers were reduced. By 90 min, changes in RL, blood pressure, plasma and BALF histamine concentrations, and circulating neutrophils and eosinophils had returned to base-line values, but platelet numbers remained significantly decreased. Sham challenge caused no significant changes in any of these variables. Intravenous administration of histamine in doses large enough to attain plasma levels comparable with those achieved after aerosol antigen challenge resulted in no concomitant rise in BALF histamine levels. We conclude that antigen challenge in sensitized dogs causes increases in BALF and plasma histamine levels and is associated with a reduction in circulating neutrophils, eosinophils, and platelets. It is likely that antigen causes airway mast cells to release mediators that move down a concentration gradient from the airways to the pulmonary circulation.

Effects of zinc sulphate on ethanol- and indomethacin-induced ulceration and changes in prostaglandin E2 and histamine levels in the rat gastric glandular mucosa.

The effect of zinc sulphate on stomach ulceration produced by ethanol and indomethacin was examined in rats. Oral or intraperitoneal pretreatment with zinc sulphate (20 mg/kg, expressed as zinc ion) strongly prevented ethanol-, but not indomethacin-induced gastric glandular ulceration. Indomethacin given beforehand did not influence the protective action of zinc sulphate against ethanol-evoked lesions. Ethanol decreased histamine levels, whereas indomethacin reduced the prostaglandin E2 (PGE2) content in the gastric glandular mucosa. The alcohol also elevated the histamine content in gastric secretion. Zinc sulphate reversed the ethanol-induced changes in histamine levels in both mucosa and secretion, but did not modify PGE2 reduction by indomethacin. Zinc sulphate also antagonised protein leakage from the stomach following ethanol administration. It is concluded that gastric ulceration by the currently employed doses of ethanol and indomethacin is caused by different mechanisms. Zinc sulphate prevents histamine-mediated lesions produced by the alcohol, but not ulceration due to PGE2 depletion by indomethacin.

Effects of antihistamines and indomethacin on hyperosmolar-induced vasodilation.

The circulatory effects of iv injections of hyperosmolar solutions were studied both in intact dogs with aortic flow probes and in dogs using a standard right heart-bypass preparation. Serial iv injections of 20 ml of 10% NaCl or 50 ml of 25% mannitol produced reproducible episodic vasodilation characterized by falls in mean aortic pressure from 99 +/- 10 (SE) to 61 +/- 6 Torr and increases in aortic flow from 2.20 +/- 0.06 1/min to 3.12 +/- 0.28 (P less than 0.01). Systemic vascular resistance decreased (P less than 0.01) with each injection and serum osmolarity increased (P less than 0.01); however, there was a poor correlation between these two variables (r = -0.24). Because the mechanism of these physiological changes is unclear, the following experiments were performed to determine whether they were due to the release of vasoactive chemical mediators. We measured arterial and venous plasma histamine, a mediator released systemically in IgE-mediated anaphylactic reactions, but found no changes in histamine levels. Furthermore, pretreatment with both H1 and H2 blockers (diphenhydramine and cimetidine), agents that blocked histamine-induced hypotension, did not prevent hyperosmolar vasodilation. Also, indomethacin (a cyclooxygenase pathway inhibitor of prostaglandin synthesis) did not affect hyperosmolar vasodilation or the fall in systemic vascular resistance. Therefore, hyperosmolar vasodilation is not caused by the systemic release of histamine or by the effects of prostaglandins. The mechanism of these reactions is unknown, but it may be due to direct local effects of hyperosmolar solutions on vascular smooth muscle, perhaps mediated by local fluid and electrolyte shifts.

HISTAMINE AND CORTISOL LEVELS IN SOME HEMATOLOGICAL DISORDERS

Whole blood (WB) and plasma (P1) histamine and P1 cortisol were determined in 20 cases of acute leukemia at diagnosis, after induction therapy and during maintenance. Twelve cases of I.T.P., 7 cases of Henoch-Schonlein purpura and 8 cases of aplastic anemia were also studied and results compared to 50 normal controls. -A significant reduction of WB and P1 histamine was found at diagnosis in acute leukemia and aplastic anemia. The depletion level, particularly in WB, was more marked in aplastic anemia cases. After onset of remission in acute leukemia, the histamine levels of WB and P1 became abnormally high; at maintenance P1 histamine returned to normal levels, while WB histamine remained high. -In I.T.P. no significant change in histamine levels was found. -In Henoch-Schonlein purpura the histamine levels were significantly elevated. -The P1 cortisol levels were significantly higher than normal in acute leukemia cases, decreased but still elevated in remission and during maintenance. They were significantly higher than normal in I.T.P., Henoch-Schonlein purpura and aplastic anemia.

A Study of Histamine in Myeloproliferative Disease

Abstract 1. Whole blood histamine content was measured in 80 patients with myeloproliferative disease. Increased levels were found in 60 per cent of patients with uncontrolled polycythemia vera, in 7 per cent of patients with polycythemia vera being controlled by myelosuppressive therapy, and in 71 per cent of a group with "spent" polycythemia, myeloid metaplasia and myelofibrosis. 2. The excretion of histamine in the urine was measured in 60 patients, 30 with elevated blood histamine and 30 with normal blood histamine. The urine findings paralleled the blood findings in 90 per cent of the cases. 3. Measurements of cell-poor and cell-rich fractions of blood showed that the histamine is contained in the white cell fraction. Elevated basophil counts were present in 50 per cent of the patients and occurred with the greatest frequency in the groups with elevated blood and urine histamine. A rough correlation between the basophil count and the histamine content of blood and white cell fractions was observed in normal subjects and most cases with myeloproliferative disease. Data obtained in some cases of myeloproliferative disease suggest that the histamine content of the basophil may be abnormal and that other granulocytes may contribute to the total leukocyte histamine. 4. Myelosuppressive agents produced a reduction in histamine (expressed per 109 myeloid cells) and a decrease in urine histamine as control of the myeloproliferative process was achieved. Treatment with phlebotomy alone produced no change in histamine levels. 5. The incidence of pruritus, upper gastrointestinal distress and urticarial manifestations was increased 7-fold, 4-fold and 12-fold, respectively, in patients with elevated histamine levels as compared with those who had normal histamine levels. 6. Cyproheptadine, a potent antihistaminic, successfully controlled pruritus, relieved pyrosis and suppressed urticarial eruptions in patients with elevated histamine levels. Suppression of the reaction to subcutaneously administered codeine (a histamine-releaser) afforded objective evidence that cyproheptadine blocked the effects of histamine release in vivo. 7. The metabolism of histamine and the role of elevated histamine levels in the clinical manifestations and pathophysiology of myeloproliferative disease are discussed.