Blood Histamine Levels Research Articles

Blood histamine levels in cotton-dust exposed workers in a textile mill of Ahmedabad.

Blood histamine levels were measured by the bioassay of histamine (on an isolated strip of guinea pig ileum) in workers exposed to cotton dust in a textile mill in Ahmedabad. Byssinotic subjects showed very high levels of blood histamine as compared to nonbyssinotic and control subjects. The blood histamine levels were not well correlated to the dust concentrations or duration of exposure but rather to the day of the week (ie, first, second, third, etc., after weekend break) on which the samples were collected. The blood histamine levels were high on the first day of the work week, when byssinotics complained most of their symptoms.

Release of prostaglandin D2 and histamine in a case of localized heat urticaria, and effect of treatments

A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway.

Plasmodium berghei-infected mice: lack of effect of meclizine and cimetidine on the development of pulmonary oedema.

The involvement of histaminergic mechanisms in the pathogenesis of pulmonary oedema observed in Plasmodium berghei-infected mice was investigated. Histamine concentrations in plasma and whole blood of infected and normal mice were determined by radioenzymatic assay during the seven days of the infection. Elevated plasma and whole blood histamine levels were found at the last stages of infection (sixth day and seventh day after ip injection of parasitized erythrocytes), showing a close temporal correlation between the development of oedema and the elevation of the circulating histamine concentrations. However, the treatment of infected mice with the H1- or H2-receptor antagonists, meclizine or cimetidine, did not change the development of pulmonary oedema. The absence of effects of H1- and H2-receptor blockers on this model is a suggestive evidence that histamine does not contribute to P. berghei-induced pulmonary oedema in mice.

Pharmacological characterization of the histamine uptake system in HL-60 human promyelocytic leukemia cells.

Serotonin and histamine H1, H2 receptor agonists or antagonists inhibited [3H]histamine uptake by HL-60 cells, according to the following order of potency: impromidine greater than 4-MH greater than histamine greater than AET greater than PEA and: cimetidine, histamine greater than diphenhydramine, serotonin. It is concluded that histamine uptake by HL-60 cells was specifically controlled by the H2 type histamine receptor and that this active process might be involved in pathophysiological regulations in leukemic and normal granulocytic precursors and in the control of histamine levels in peripheral blood and tissues in man.

Acute hemodynamic effects of an antitumoral agent: elliptinium. Involvement of histamine release

This work reports a study of cardiovascular effects of elliptinium, a recently-acquired antitumoral agent, acutely administered i.v. in the dog. Its hemodynamic effects (10 parameters) are detailed, and their mechanism of action is investigated by antagonist administration and determination of blood and plasma histamine levels. Elliptinium induces vasodilation and tachycardia. The former is mainly due to histamine release, and a brief and slight release of prostaglandins; the latter is due to a reflex to hypotension and release of catecholamines. These results agree with others using various compounds of the ellipticine family and anthracycline antitumoral agents. They suggest treatment to prevent anaphylactoid side effects observed with this drug in man and they raise the question of the usefulness, in antitumoral agent, of histamine releasing properties.

Acute hypotension due to platelet serotonin-induced chemoreflexes after intravenous injection of dextran sulfate in the rabbit.

The hypotension and bradycardia observed after intravenous injection of dextran sulfate in rabbits was prevented by prior depletion of circulating platelets, but was not prevented by depletion of the third component of complement or Hageman factor. Dextran sulfate injection caused immediate thrombocytopenia with temporary localization of platelets within lungs. Morphological analysis revealed platelet aggregates in lung capillaries. The platelets had changed shape and were in the process of degranulating. Serotonin and histamine levels in blood increased approximately 5-fold and 7-fold, respectively, after dextran sulfate injection. The cardiovascular events following dextran sulfate injection were mimicked by intravenous serotonin but not by intravenous histamine injection, although a combination of serotonin and histamine reproduced the pattern of blood pressure changes better than did either agent alone. Quantification of platelets trapped in lung revealed that the potential release of serotonin from trapped platelets could account for the rise in plasma serotonin concentration and the hemodynamic changes observed. Both the dextran sulfate-induced cardiovascular effects and serotonin-induced hypotension were markedly diminished by cutting vagus and depressor nerves, and were virtually abolished by carotid ligation in addition to nerve section. These results support the concept that platelet activation within rabbit lungs may cause hypotension via serotonin-induced chemoreflexes.

Vecuronium—The First Years

Summary The monoquaternary aminosteroidal compound, vecuronium bromide, is a potent non-depolarizing neuromuscular blocking drug with a duration of action which is 2–3 times shorter than that of pancuronium. Spontaneous recovery from muscle paralysis is predictably rapid and there is little evidence of cumulative effect following its administration over several hours by multiple injections or continuous infusion. When appropriate, neuromuscular transmission can be readily restored by anticholinesterase agents. Vecuronium is free from significant cardiovascular side-effects and, when twice the recommended intubating dose is given, the blood histamine levels remain within normal limits. It would appear that the drug is rapidly cleared from the plasma, mainly as a result of hepatic uptake and consequent biliary excretion. Renal mechanisms are of much less importance in the elimination and therefore, since the neuromuscular blockade is not prolonged, there is no contraindication to the use of this relaxant in patients with renal impairment. In comparison with the established neuromuscular blocking drugs, vecuronium would seem to represent a significant advance in that controlled relaxation can be readily maintained during surgical procedures extending in duration from some 20 minutes to many hours, without risk of prolonged recovery or unwanted side-effects.

Action de la tritoqualine sur le taux d'histamine du sang total

For ten years now, tritoqualine, a histidine decarboxylase inhibitor, has been advocated in a prevention protocol for anaphylactoid reactions occurring during general anaesthesia. The present double-blind study aimed to quantify the effects of the drug on whole blood histamine levels. 44 patients were assigned at random to two different groups, one taking 300 mg t.i.d. tritoqualine for three days, and the other taking a placebo. The histamine levels were measured before the treatment and 12 h after the last dose of the drug after haemolysis of the sample, by the fluorometric technique preceded by column chromatography. In the group taking tritoqualine, the histamine level fell from a mean of 109±61 to 91±41 ng · ml −1, whereas it rose from a mean of 92±55 to 105±62 ng · ml −1 in the control group taking placebo. These variations were not statistically significant. In both groups were present four volunteers with a history of allergy; their histamine level fell from 107±35 to 71±36 ng · ml −1 after tritoqualine intake (p <0.05), whereas it rose from 76±19 to 162±36 ng · ml −1 after placebo (p <0.05). The small differences found in the whole blood histamine level 12 h after the last oral dose of the drug suggested that the present tritoqualine dose regimen was inadequate to achieve the aims of its prescription.

Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

Histamine release caused by drugs and/or their solvents is a well known phenomenon. In this study, both in vivo (anaesthetized and conscious dogs) and in vitro (isolated rat peritoneal, human and guinea-pig lung mast cells) models were used. Cremophor E1 and six derivatives of 12-hydroxystearic acid were compared for their histamine releasing abilities. Although the three types of isolated mast cells responded similarly, histamine release being observed with DH (the diester of 12-hydroxystearic acid with polyethylene glycol), TN (12-hydroxystearic acid polymerized with ethylene oxide) and ME (the monoester of 12-hydroxystearic acid esterified with polyethylene glycol), the anaesthetized dog exhibited elevated blood histamine levels and clinical symptoms after administration of all the solubilizing agents, except TN and ME. The reasons for this discrepancy are not known. The addition of the drugs (Althesin or propanidid) to their solubilizing agents caused histamine release, which was not observed with the solubilizing agent alone. This is the first demonstration of an in vitro model, which copies the clinical situation, i.e. solvent does nothing but the solvent plus drug combination causes histamine release and hence adverse reactions.

Histamine levels in stored human blood.

The histamine content in plasma samples obtained from a group of healthy blood donors, from blood stored in citrate-phosphate-dextrose supplemented with adenine (CPDA) packs for up 28 days, and from the side arm of a transfusion line was measured by radio-enzymatic assay. Healthy donors had a mean plasma histamine content of 0.79 ng per ml. Blood stored in CPDA initially showed a similar histamine level (0.69 ng/ml on day 3 of storage), but there was a progressive rise with time, and at 28 days, the level was 20.5 ng per ml. The increase in histamine is best described by a positive exponential and may be explained by a process whereby the plasma histamine level increases the degree of histamine release from blood cells. The histamine levels in the blood infused into patients tended to be higher than those found in the stored units of the same age, if these packs were less than 7 days old. This may have been caused by the unit becoming warmer during transfusion. We speculate that the histamine levels in the older units of stored blood were high enough to cause or augment transfusion reactions and that the storage age of blood may have a bearing on the incidence of transfusion reactions.

Relationship of histamine in tissues and antiparasitic substances in gastrointestinal mucus to the development of resistance to trichostrongyle infections in young sheep

The development of resistance to nematode infection and self-cure in a flock of young grazing sheep were examined in relation to changes in the levels of histamine in tissues and levels of antiparisitic substances in gastrointestinal mucus. Analysis of faecal egg counts showed that when the sheep were ranked according to individual mean monthly egg counts there was a significant trend to similar rankings in successive months. Sheep with high and low egg counts were slaughtered at monthly intervals for examination and comparison. Histamine levels in blood and intestinal conten ffluids were similar in both groups of sheep and were highest during maximum challenge by larval nematodes. Antiparasite activity of the intestinal mucus was significantly higher in sheep with low egg counts than those with high counts, between January and May, and was associated with significantly lower burdens of fourth stage larvae.

Lysophosphatidylserine as histamine releaser in mice and rats.

Lysophosphatidylserine is a specific inducer of histamine release in isolated mast cells. To determine whether a similar effect is manifest in vivo, the phospholipid was injected (1-5 mg/kg i.v.) into mice and rats. A dose-dependent rise in blood histamine was observed in both animals. The several-fold increase in blood histamine occurred in the first minutes and was followed by a slower decline toward normal values. A second dose of lysophosphatidylserine was without effect. Systemic manifestations (depression, hypothermia, hypotension) were associated with the increased blood histamine level. When the tissue histamine stores accessible to lysophosphatidylserine were previously decreased by repeated phospholipid injections, no systemic symptoms occurred. Mobilization of carbohydrate reserves was also manifest during the action of lysophosphatidylserine. Prior treatment with compound 48/80 induced sustained refractoriness to lysophosphatidylserine. Structure-activity relationship demonstrated that the property to induce histamine release was linked to the structure of serine head group. Thus, other natural phospholipids or lysophospholipids were inactive. It is concluded that in analogy with the effect seen in vitro lysophosphatidylserine produces in vivo release of mast cell histamine.

Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: Relevance of circulating basophils to measurements of plasma histamine

The relationship of airway cooling during exercise to changes in airway caliber, plasma histamine levels, and circulating basophils was investigated in eight allergic asthmatic and eight normal subjects. In asthma matched RHE during exercise and ICH produced almost identical bronchoconstriction with maximum falls in sGaw of 61.0 ± 4.5% and 57.9 ± 5.2%, respectively. A similar RHE in normal subjects was associated with a 7.9 ± 3.3% fall in sGaw. The resting plasma-histamine levels were higher in the asthmatic (0.52 ± 0.06 ng/ml) than in the normal (0.31 ± 0.07 ng/ml, p < 0.05) subjects. No significant change in plasma histamine occurred after exercise in either group nor in the asthmatic subjects with ICH. In contrast, exercise but not ICH stimulated an increase in leukocytes, basophils, and total blood histamine in parallel with the airway response that reached a maximum at 2 to 5 min in both normal and asthmatic subjects. There was a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p < 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 ± 2%) than in normal subjects (6.46 ± 7%, p < 0.005), which is consistent with the higher resting plasma-histamine levels in the asthmatic subjects. These findings suggest that plasma-histamine changes with exercise in asthma but not ICH may be related to the associated basophilia and sample handling rather than intrapulmonary mast cell degranulation.

The determination of blood histamine in asthmatic patients with a simple and sensitive method.

The histamine level of whole blood and plasma in asthmatic patients was estimated by means of a simple, sensitive and specific method, which was developed to measure low histamine levels. This method consists of the following procedures; the partial purification of histamine with a small P-cellulose column; its further purification with high performance liquid chromatography (HPLC); and fluorometric detection with precolumn o-phthaldehyde (OPT) reaction. The present assay could detect as little as 0.5 ng of histamine concentration. Blood histamine levels in patient with asthmatic attack, 57 +/- 34 ng/ml (mean +/- S.D. N = 14), were significantly different from those in symptom-free period, 37 +/- 15 ng/ml (N = 15) as well as those in normal subjects, 36 +/- 17 ng/ml (N = 12). However, there were no significant differences among plasma histamine levels in normal subjects, 1.6 +/- 1.7 ng/ml (N = 12) and, in asthmatic patients during attacks, 1.6 +/- 1.8 ng/ml (N = 14) and symptom-free periods, 1.6 +/- 1.7 ng/ml (N = 15). These results indicate that plasma histamine concentration does not increase during asthmatic attacks, even though there was significant increase of blood histamine concentration.

Blood histamine level in rats with hydralazine-induced collagen-like syndrome

LE-positive collagen-like syndrome was produced in rats with chronic hydralazine treatment. An increase in histamine level in total blood and serum was found in the hydralazine-treated animals.

Seasonal variations of total histamine in patients with seasonal allergic rhinitis.

Seasonal variations of total blood histamine were examined in twenty patients with seasonal allergic rhinitis (Japanese cedar pollinosis). In blood specimens taken in the pollen season of 1978, the symptom-free season of 1978, and the pollen season of 1979, the mean values of blood histamine were 61.6, 50.0 and 84.2 ng/ml respectively. The differences in blood histamine levels between the pollen season of 1978 and the symptom-free season of 1978 and between the symptom-free season of 1978 and the pollen season of 1979 were statistically significant. In the symptom-free season of 1978, the blood histamine levels of twenty normal subjects were also examined; the mean value was 58.2 ng/ml. The blood histamine levels of the patients in the symptom-free season were not statistically different from those of the normal subjects.

Decreased blood histamine levels in patients with solid malignant tumours.

In a one-year follow-up study, 444 blood histamine determinations were performed in 163 patients with solid malignant tumours. Compared with normal subjects, blood histamine levels were significantly lower in patients with unresected primary tumours (30.7 +/- 19.9 ng ml-1), metastases (34.1 +/- 17.1 ng ml-1), or both (24.5 +/- 12.8 ng ml-1). By contrast, after successful tumour resection, histamine blood levels were nearly normal (52.1 +/- 18.4 ng ml-1, versus 59.6 +/- 22.6 in control patients). Stability of the histamine blood levels was associated with stability of the disease. A progressive decrease in histamine blood levels preceded clinical relapse or detection of metastasis. In patients with consecutive histamine blood levels which were less than 15 ng ml-1, survival did not exceed 2 months. In patients with gastrointestinal tumours, blood histamine levels provided information additional to that derived from serum CEA determination. In patients with non-gastrointestinal tumours, the blood histamine level may be of more value than CEA as a marker of disease progression.

Histamine release and hypotensive reactions in dogs by solubilizing agents and fatty acids: analysis of various components in cremophor El and development of a compound with reduced toxicity.

Anaphylactoid reactions in man following administration of drugs solubilized with cremophor El (polyethylenglycolglycerol riconoleate) are a considerable clinical problem. Since these reactions occur in dogs on first exposure and in pigs on second exposure, the 'dog model' was used in this communication to analyse components and chemical modifications of cremophor El and its components for their clinical effects, their hypotensive actions and their histamine-releasing capacity. Two series of experiments in 1978 and 1980 were performed in 144 adult mongrel dogs of both sexes. In these studies histamine release was not related to the effect of the solubilizing agents as tensides and was elicited by rather low doses (about 10--100 mg/kg i.v.). The effect of these substances on blood pressure and on blood histamine levels was connected with distinct chemical features: the most potent compounds were oxethylated and additionally esterified unsaturated or hydroxylated fatty acids. Several phases in hypotensive reactions were observed, including an immediate response, a delayed blood pressure response and a late response about 15--20 min after injection. Only the delayed response was associated with histamine release. The combination of cardiovascular effects and histamine release was fatal on some occasions indicating that histamine release can be dangerous. Compared to cremophor El, the tenside effect was equal, but the toxicity was reduced in oxethylated 12-hydroxystearic acid. It is recommended that this solubilizer should be used in further extended studies in animals and - if these are successful - in clinical trials.

Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels.

1. Neurotensin stimulated histamine release and granule extrusion when applied to isolated rat peritoneal mast cells. 2. This secretory response was prevented by the removal of calcium or energy and was not accompanied by the release of lactic dehydrogenase. 3. The secretory response produced by neurotensin was prevented by prior treatment of mast cells with cromoglycate. 4. The intravenous injection of neurotensin into anaesthetized rats produced a rapid and significant increase in the level of blood histamine that was dependent upon the dose of neurotensin. 5. Treatment of rats with compound 48/80, 24 hr before neurotensin, abolished the elevation in blood histamine caused by neurotensin. The intravenous injection of cromoglycate 1-2 min before neurotensin greatly reduced the response to neurotensin. 6. The intradermal injection of neurotensin (0.03-30 p-mole) increased capillary permeability in rats pre-treated intravenously with Evans Blue. This response was abolished by the antihistamine, diphenhydramine. Increasing the dose of neurotensin to 300 p-mole partially overcame this inhibition by diphenhydramine. 7. Our results demonstrate that neurotensin can elicit an exocytotic secretory response from isolated rat peritoneal mast cells and elevate histamine levels in blood. It is suggested that some of neurotensin's physiological effects may be due to stimulation of mast cell secretion.

Nippostrongylus brasiliensis infection in the rat: effects of surgical removal of Peyer's patches, mesenteric lymph nodes and spleen.

The influence of the surgical removal of Peyer's patches, mesenteric lymph nodes and spleen has been examined on the host response to Nippostrongylus brasiliensis infection in the rat. In animals subjected to these procedures, no effects were observed on whole blood or plasma histamine levels, peripheral blood leucocytosis or reaginic antibody levels, intestinal mast cell numbers or histamine content, nor on faecal egg output.