Histamine Tolerance Research Articles

WITHDRAWN: Elevated histamine etiology model for most major vaccine associated adverse events including SARS-CoV-2 spike vaccines

Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. Many of these adverse events symptoms overlap symptoms associated with elevated histamine levels. Based on these observations, the hypothesis that the majority of vaccine associated reactogenicity adverse events are caused by temporal histamine intolerance in vaccinees is proposed. This hypothesis is based on a model of innate immune responses releasing a surge of inflammatory molecules including histamine; this surge is hypothesized to exceed the normal histamine tolerance level for vaccinees with reactogenicity adverse events. Further, these symptoms resolve as histamine levels fall below the vaccinee's tolerance threshold. This model can be evaluated by the detection of elevated histamine levels in vaccinees corresponding to timing of symptoms onset. If confirmed, a direct consequence of this model predicts that some antihistamine treatments, mast cell stabilizers, and possibly diamine oxidase enzyme may reduce the incidence or severity of adverse events experienced by vaccinees post vaccinations for most or all high reactogenicity vaccines including coronavirus disease 2019 (COVID-19) Spike vaccines.

Vaccines Associated Cardiac Adverse Events, Including SARS-Cov-2 Myocarditis, Elevated Histamine Etiology Hypothesis

Background: Rare cardiac adverse events are reported post vaccinations. For the SARS-CoV-2 mRNA Spike vaccines, higher numbers of these cardiac adverse events are being reported with myocarditis disproportionately occurring in younger males. The etiology of these cardiac adverse events associated with vaccines including SARS-CoV-2 is unknown. The etiology of the higher frequency of these cardiac adverse events temporally associated with SARS-CoV-2 mRNA Spike vaccines is also unknown. Aim: Data mine vaccine associated cardiac adverse events to gain insights into COVID-19 mRNA associated myocarditis and pericarditis adverse events. Methods: All adverse events, with a focus on cardiac adverse events, were summarized from the Vaccine Adverse Event Reporting System (VAERS) for all vaccines from 1990 to April 1, 2022. Results: Analogous patterns of cardiac adverse events were observed for multiple unrelated vaccines with occurrences proportional to vaccine reactogenicity level defined all adverse events. This article proposes the hypothesis that innate immune responses to vaccines cause elevated histamine levels post vaccination; the histamine level reached may exceed the vaccinees’ histamine tolerance level for several days, with the histamine level likely correlating with the vaccine reactogenicity level. Further, it is proposed that the elevated histamine level is causative for the reported cardiac adverse events. For myocarditis and pericarditis reported adverse events, the elevated histamine levels may induce cardiac capillary pericyte vasoconstrictions followed by localized ischemia and anoxia; this is followed by the release of troponin from myocyte cells affected by anoxia. This hypothesis is supported by the temporal onset timing of adverse events reported following SARS-CoV-2 mRNA Spike vaccinations in VAERS. Conclusion: Onset of cardiac adverse events immediately following vaccinations for multiple unrelated vaccines may implicate elevated histamine levels from immune responses as causative for these adverse events. Relevance for patients. An etiology model for cardiac adverse events temporally associated with vaccination is proposed. If validated, this model identifies possible candidate treatments for evaluation with the potential to reduce the severity and frequencies of these cardiac adverse events for vaccinees.

Detection of Extended Spectrum Beta-Lactamase Escherichia coli and Histamine Contents in Raw Mackerel (Scomber japonicus) Sold in Open Markets in Sagamu, Nigeria

Background: A food borne sickness called histamine fish poisoning is frequently brought on by eating some fish species that have high levels of histamine and other biogenic amines in their tissues. When fish is improperly stored and preserved, its natural makeup makes it polluted. Objectives: This study was carried out to examine the histamine contents, determine the extended-spectrum beta-lactamase producing isolates of Escherichia coli from the gut of raw mackerel fish obtained in Sagamu markets and relate the plasmid isolated, if present, with Extended Spectrum Beta Lactamase (ESBL). Materials and Methods: Fifty (50) mackerel fish were dissected and their guts were removed for the isolation of E. coli on eosin methylene blue agar medium. The isolates obtained were Gram stained, biochemically characterized, and thereafter plated on Mueller Hinton agar impregnated with ESBL discs by double disc synergy methods. Ten gram (10 g) of each part of fish weighing 100 g was blended for histamine determination by spectrophotometry and plasmid analysis of some selected ESBL resistance amongst the isolates were determined. Results: Escherichia coli were found in all fifty mackerel fish and 31 (62%) of those were ESBL producers. All of these were plasmid-free. In 14 (28%) of the 50 fish analysed, histamine concentrations of more than 100 mg/100 g exceeded the tolerance threshold of 10 mg/100 g, Conclusion: The results from the study showed that some of the fish sold in the markets of Sagamu contain ESBL producing Escherichia coli which may be considered as reservoirs for resistant bacteria. Significant level of histamine recorded surpassed histamine tolerance level in fish for human consumption. There is a need to provide storage facilities and raise hygiene awareness in markets where fish is sold.

Etiology model for many vaccination adverse reactions, including SARS-CoV-2 spike vaccines

<abstract><sec> <title>Objective</title> <p>Vaccinated individuals (vaccinees) experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. The number of vaccine adverse reactions is higher for SARS-CoV-2 spike vaccines than all other vaccines. Can data analysis of vaccine adverse reactions responses provide etiology insights for high reactogenicity vaccines?</p> </sec><sec> <title>Methods</title> <p>The Vaccine Adverse Event Reporting System (VAERS) database was data mined for all vaccine adverse events data by vaccine, age, gender, dose, and day of onset post vaccination. Results for vaccines with the highest number of adverse events were compared.</p> </sec><sec> <title>Results</title> <p>For vaccines and adverse events with the highest numbers of reports, the day of onset approximates a power of two decay pattern for the first three days. The consistency of this pattern for multiple unrelated vaccines narrows possible etiology mechanisms. Many of these adverse event symptoms overlap symptoms associated with elevated histamine levels. Herein, innate immune responses and specifically elevated histamine levels are proposed to be causative for the majority of these adverse events. This hypothesis is based on a model of innate immune responses releasing a surge of inflammatory molecules, including histamine; this surge is hypothesized to exceed the normal histamine tolerance level for vaccinees causing reactogenicity adverse events. Further, these symptoms resolve as histamine levels fall below the vaccinee's tolerance threshold. This model can be evaluated by the detection of elevated histamine levels in vaccinees corresponding to timing of symptoms onset. If confirmed, a direct consequence of this model predicts that specific antihistamine treatments, mast cell stabilizers, and possibly diamine oxidase enzyme may reduce the incidence or severity of adverse events experienced by vaccinees post vaccinations for most or all high reactogenicity vaccines including coronavirus disease 2019 (COVID-19) spike vaccines.</p> </sec><sec> <title>Conclusions</title> <p>The reported onset occurrences of the majority of reported adverse events are consistent with the likely etiology of innate immune responses to vaccinations for vaccines with higher reactogenicity levels. Herein, the hypothesis is proposed that the majority of these adverse events result from a histamine surge that temporarily exceeds the vaccinee's tolerance level.</p> </sec></abstract>

Medikamentenunverträglichkeit bei Histaminintoleranz und Mastozytose: «facts and fictions»

Drug hypersensitivity in patients with presumed histamine intolerance and mast cell activation disease Abstract. There is no evidence to suggest that sensitization against drugs occurs more frequently among patients with presumed histamine intolerance compared to patients with normal tolerance to histamine. However, preclinical data suggest interactions between some drugs and histamine catabolism. Nevertheless, the clinical relevance of these findings remains unclear as histamine in humans can be catabolized by different pathways. There are no drugs for which induction or worsening of histamine intolerance has been established clinically. In patients with mastocytosis an increased rate of sensitization and specific allergies to drugs is unlikely. However, pathophysiologic understanding suggests that mast cell activation disease might enhance drug reactions, which are induced by mast cell degranulation. Additionally a possible lower threshold for unspecific mast cell degranulation in patients with mastocytosis could lead to pseudoallergic drug reactions. However an increase in the number of drug substances triggering such reactions is not expected. Nevertheless, there are lists of drug substances which are assumed to cause anaphylactic / anaphylactoid reactions especially in patients with mastocytosis. Conversely, these lists are rarely based on clinical evidence. A recently published prospective trial did not find any relevant increase of acetyl salicylic acid hypersensitivity in patients with mastocytosis. Patients with mastocytosis and a history of drug hypersensitivity should be thoroughly assessed by an allergological workup and advised to avoid triggering and / or cross reactive drug substances. We recommend that these patients avoid drugs which may interfere with the treatment of anaphylaxis like beta blockers, certain antidepressants or Catechol-O-methyltransferase inhibitors because of the increased risk for enhanced hypersensitivity reactions.

Psychological and Respiratory Physiological Effects of a Physical Exercise Programme on Boys with Severe Asthma

Ten boys 9-12 years of age with severe perennial asthma participated in a physical exercise programme lasting 8 months. Pulmonary function and psychological tests were performed before training, immediately after, and one year after the end of the exercise programme. Static lung volumes, flow-volume variables and histamine tolerance were used as indicators of pulmonary function. Ego structure, body image, social development and concentration capacity were used as indicators of personality development. Before the study, the group had high FRC (p less than 0.05) and RV (p less than 0.001), low FEV1, MEF50 and MEF25 (all p less than 0.001) and low histamine tolerance. They showed marked disturbances in their personality development with low scores in psychological variables. During the training period, MEF50 and MEF25 increased slightly (p less than 0.01). Marked improvement was observed in all psychological variables (p less than 0.001). The positive effects remained during the following year. The marked and lasting improvement in personality development was regarded as an essential factor behind the more modest positive clinical and pulmonary function changes. The results emphasize the importance of including exercise programmes in the treatment of children with asthma.

Airways responsiveness determined by consecutive histamine challenges in asymptomatic asthmatics.

The effect of two consecutive histamine inhalation challenges on airways responsiveness was assessed in a group of eight nonsmoking nonmedicated asthmatics aged 19-27 yr. All subjects had a base-line forced expiratory volume in 1 s (FEV1) of greater than 80% of their predicted normal value before the initial challenge and were allowed to recover to greater than 95% of the initial base-line FEV1 value before the second challenge was initiated. The average airways recovery time after the first challenge was 44 min but ranged between 30 and 90 min. The mean +/- SD values of cumulative histamine dose units provoking a 20% decrease of the FEV1 from the buffer control value (PD20FEV1) were 10.79 +/- 5.95 determined with the first and 30.50 +/- 46.36 with the second challenge (P greater than 0.05). We conclude that sequential histamine challenges performed in mild asthmatics with closely controlled prechallenge airways function are well tolerated. Although some variance does exist in intersubject airways recovery time and in intra-subject histamine airways responsiveness determined by sequential challenges, our data do not support recent observations (J. Appl. Physiol. 63: 1572-1577, 1987) that histamine tolerance is a characteristic finding associated with bronchial asthma.

Effects of chronic treatment with histamine on catecholamine content and synthesis in rat brain, heart and adrenals

Chronic treatment with increasing doses of histamine rendered rats tolerant to the hypothermic and toxic effects of this amine. The development of this tolerance was associated with a gradual decrease in endogenous epinephrine (EPI) content, increase in norepinephrine (NE) concentration and tyrosine hydroxylase activity in the adrenals. In contrast, cardiac NE depletion occurred rapidly after both acute and chronic histamine administration. Brain NE level increased and tyrosine concentration decreased, but only after establishment of histamine tolerance. The presently observed central involvement of catecholamines in histamine tolerance may represent a compensatory mechanism in response to peripheral catecholamine depletion.

Effect of splenectomy on the resistance of rats to histamine stress.

THE spleen has been suggested by many investigators as a site of production of hormones or hormone-like substances ; interrelationships have been postulated with the pituitary, adrenal, gonad and thyroid glands. The present communication on the relationship of histamine tolerance to splenectomy provides additional evidence for a splenic humoral contribution.

The effects of reserpine on histamine tolerance and endocrine organs of the rat.

ABSTRACT Reserpine administration resulted in a rise in histamine tolerance of male rats as evidenced by a rise in histamine LD50. This increase in histamine LD50 is characteristic of small doses of reserpine; larger doses resulted in an increased treatment of period mortality, marked endocrine and body weight losses.

Releasable histamine levels and histamine tolerance in tissues of 291 psychotic patients.

1. Skin histamine, releasable on intradermal injection of curare, and tolerance to intradermally injected histamine have been studied in 291 mental patients and 51 normal subjects. 2. The data were analyzed statistically for the effect of sex, age, duration of hospitalization, drug treatments and diagnosis. Data from patients were also compared with normal subjects. 3. Releasable skin histamine was the same in male and female patients but tolerance to histamine was greater in males. 4. Age did not affect releasable skin histamine levels except in the 50-59 year old group as compared with the over 60 group. The difference was not striking but indicated a trend toward less skin histamine in the older age group. Tolerance to injected histamine was not affected by age. 5. Duration of hospitalization, which may be a rough approximation of duration of mental illness did not alter skin histamine content or tolerance to histamine. 6. Reserpine lowered skin histamine very considerably and was unique among the tranquilizing drugs in this property. Both reserpine and chlorpromazine increased the tolerance to histamine. 7. Schizophrenics and manic-depressives did not differ in skin histamine levels or response to intradermally injected histamine. 8. Patients receiving reserpine therapy had a lower level of skin histamine than normals, but patients not receiving drugs and patients receiving drugs other than reserpine did not differ from normals in releasable skin histamine. Histamine tolerance was greater in patients receiving drugs in general, or reserpine in particular, than normal individuals. Normal individuals and patients not receiving drug therapy gave similar responses to intradermally injected histamine. 9. An hypothesis is suggested for reconciling the infrequency of allergic reactions in psychotics with essentially normal releasable skin histamine and normal tolerance to intradermally injected histamine.

Relation between histamine tolerance, visual autokinesis, Rorschach human movement, and figure drawing.

Relation between histamine tolerance, visual autokinesis, Rorschach human movement, and figure drawing.

Acute KCI and histamine tolerance and adrenal weight in x-irradiated mice.

ArticleAcute KCl and Histamine Tolerance and Adrenal Weight in X-Irradiated MiceWillie W. SmithWillie W. SmithFrom the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Public Health Service, Federal Security Agency, Bethesda, MarylandPublished Online:31 Oct 1951https://doi.org/10.1152/ajplegacy.1951.167.2.321MoreSectionsPDF (906 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation More from this issue > Volume 167Issue 2October 1951Pages 321-327 Copyright & PermissionsCopyright © 1951 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1951.167.2.321PubMed14894654History Received 3 August 1951 Published online 31 October 1951 Published in print 31 October 1951 Metrics

Studies on histamine and histamine antagonists

1. 1. The results of some experiments on histamine and antihistaminic drugs in allergic patients were reported. 2. 2. A histamine release from allergic skin reactions was shown. 3. 3. A disturbed histamine metabolism was shown in allergic patients by an increase of blood histamine after histamine injection (histamine tolerance curve) and physical exercise. No significant change or a decrease was noted in normal persons under similar conditions. Some treatments (fever therapy, antihistaminic drugs) inhibit the increase of blood histamine and the allergic symptoms produced by histamine injection in allergic patients. 4. 4. In regard to histamine antagonists a constant inhibition of allergic reactions after oral and intravenous administration of these drugs was observed. Other experimental researches were reported. 5. 5. Significant symptomatic relief in many allergic manifestations was obtained in 84 of 140 allergic patients (60 per cent).

Effect of Ergotamine Tartrate on Potassium Changes in Histamine Shock.

SummaryErgotamine tartrate in the dosage used did not significantly modify serum potassium changes characteristic of histamine shock in the rat. It did not influence histamine tolerance in either the normal or the demedullated animal.

An investigation of the question of histamine tolerance

1. 1. The subcutaneous administration of histamine to dogs with total gastric pouches does not result in tachyphylaxis, as measured by the gastric secretory response. 2. 2. A gradual reduction in gastric secretory response is noted in the total pouch dogs when histamine is administered (1) at three-hour intervals, (2) twice a day for a four-day period, and (3) eight to twelve times a month for a six-month period. 3. 3. Under similar conditions, Heidenhain pouch dogs do not show this decreasing response, nor do they show a decreasing response when histamine is given twice daily, on alternate days, for three weeks. 4. 4. It may be concluded that the decreasing response noted in total pouch dogs is related to the greater loss of gastric juice and to the poorer reserve nutrition of the total pouch dogs. 5. 5. The opinion is expressed that animal experiments have so far failed to provide an experimental analogy for the therapeutic effect claimed for histamine “desensitization” in allergy.

Histamine tolerance and anaphylactic death in sensitized guinea pigs: Karady, E. S.: J. Immunol. 41: 1, 1941

Histamine tolerance and anaphylactic death in sensitized guinea pigs: Karady, E. S.: J. Immunol. 41: 1, 1941

Histamine Tolerance and Anaphylactic Death in Sensitized Guinea-Pigs

Abstract A number of cases have been reported where, due to treatment with histamine, man and animals have shown that subsequent to such treatment they were better able to overcome the effects of histamine injected experimentally, or released in the tissues as the result of cell damage (1–15). Most of the evidence that tolerance is actually produced by such treatment is of an indirect nature. The prevention of anaphylactic shock (5, 6, 9, 10), surgical shock (8), clinical manifestations of various types of hypersensitivity (11–15), and the diminution of uterine muscle response (9, 10) to histamine have been offered as valuable support not only for the theory that the tissues are better able to withstand the release of histamine as the result of pretreatment with this substance, but also that histamine is concerned in the mechanism of these various reactions.

THE USE OF HISTAMINE IN RHEUMATOID ARTHRITIS

Article1 May 1940THE USE OF HISTAMINE IN RHEUMATOID ARTHRITISR. O. MUETHER, M.D.R. O. MUETHER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-11-2147 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThere can be little doubt that arthritis and allied conditions are assuming a deservedly more important place in the thoughts of both the clinician and the research worker. In spite of much recent work, however, a satisfactory basis for treatment has not been established, and some treatments are expensive and complicated. Fever therapy, hydrotherapy, etc., seem to give great relief but are difficult of attainment under ordinary circumstances. The production of artificial jaundice advocated by Hench is difficult to obtain because of its dangers and expense.1, 2, 3, 4It is true that certain forms of physical therapy can be...Bibliography1. HENCH PS: Analgesia accompanying hepatitis and jaundice in cases of chronic arthritis, fibrositis and sciatic pain, Proc. Staff Meet. Mayo Clin., 1933, viii, 430. Google Scholar2. SIDELABRAMS NMI: Jaundice in arthritis—its analytic action, New England Jr. Med., 1934, ccx, 181. CrossrefGoogle Scholar3. HENCH PS: Effects of jaundice on arthritis, Arch. Int. Med., 1938, lxi, 451. CrossrefGoogle Scholar4. THOMPSONWYATH HEBL: Experimentally induced jaundice, Arch. Int. Med., 1938, lxi, 481. CrossrefGoogle Scholar5. DEUTSCH D: Histamine in the therapy of rheumatic diseases, Med. Klin., 1931, xxvii, 1491. Google Scholar6. KLING DH: Treatment of myositis, arthritis and disturbance of peripheral circulation with histamine cataphoresis, Arch. Surg., 1934, xxix, 138. CrossrefGoogle Scholar7. KLING DH: Histamine therapy of rheumatic affections and disturbances of the peripheral circulation, Ann. Surg., 1934, xcix, 568. CrossrefGoogle Scholar8. KLINGSASHIN DHD: Histamine iontophoresis in rheumatic conditions and deficiencies of peripheral circulation, Arch. Phys. Therap., X-Ray and Radium, 1937, xviii, 333. Google Scholar9. SHANSONEASTWOOD BCB: The use and action of histamine in rheumatism, Lancet, 1934, i, 1226. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: St. Louis, Missouri*Received for publication September 28, 1938.From the Arthritis Division, St. Louis University Group of Hospitals. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClinical Uses of Histamine and Histaminase-An EvaluationAn investigation of the question of histamine tolerance 1 May 1940Volume 13, Issue 11Page: 2147-2153KeywordsArthritisHistamineHyperthermiaRheumatoid arthritis Issue Published: 1 May 1940 PDF downloadLoading ...