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PubMed1980

[Comparative study of the toxic, anaphylactoid, and sensitizing properties of 5-sulfo-8-mercaptoquinolinates of metals of the 8th and 3d groups of the periodic table].

Pronounced allergizing action of the compounds of group VIII metals of the periodic system, observed in occupational pathology and commencement of their wide clinical application as cancerostatic agents require a comprehensive study of the properties of these substances. Anaphylactoid, toxic and genuine sensitizing action of 5-sulfo-8-mercapto-quinolinates of group YIII metals and those of group III metals having similar properties was studied and compared with reference to 8 compounds. It was shown that histamine liberation from mast cells induced by these substances as well as inhibition of the respiration of mast cells depend on the central atom and electronic structure of the ligand. The mechanism of histamine liberation observed was similar to that of specific antigen and was related to the preservation of the respiratory processes, the system of microtubules and cell cyclic nucleotides. The compounds tested were also capable of sensitizing the animal in intracutaneous injection of the substance without exogenous carrier. Sensitization developed according to the reaction of both the immediate and delayed types.

Allergens↗
PubMed1979

Histamine-releasing effect of a corticotrophin derivative. II. Mechanism of action of histamine release by C 44 680-Ba, compared with that of Cpd. 48/80, dextran and triton.

The mechanism of the histamine-liberating action of the synthetic polypeptide C 44 680-Ba, an alkyl-prolyl derivative of beta 1-19 corticotrophin, was investigated and compared with those of Compound 48/80, dextran, Melittin and Triton X-100. It was found that the release of histamine from rat peritoneal cells induced by the polypeptide is dependent on temperature, pH, calcium ions and energy-providing processes. In regard to these criteria, the mode of action of this histamine liberator resembles that of Compound 48/80 but is quite distinct from that of the unspecific substance Triton X-100.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Mast cell heterogeneity in man: unique functional properties of skin mast cells in response to a range of polycationic stimuli.

Human mast cell heterogeneity was assessed by histochemical and detailed functional criteria using mast cells isolated from foreskin, uterine myometrium and lung parenchyma. The skin mast cells were histochemically distinct from their counterparts in the other two tissues by being predominantly insensitive to blockage of dye-binding following formalin fixation (ca. 80%). Functionally, a wide range of structurally diverse polycationic compounds induced selective histamine release from the skin mast cells (ca. 10% at top concentrations) although these cells were less responsive to immunological ligands and calcium ionophores when compared with the uterine and lung cells. The basic compounds, polyarginine and histone, proved to be more generalised histamine liberators as compared with their structural analogues, polylysine and protamine sulphate, probably by virtue of their high content of arginine residues and hydrophobic nature (histone). Studies with the anaphylatoxin, C3a, and its analogues 21R and C3ades Arg on skin mast cells emphasized the importance of basic amino acids for histamine-liberating peptides. Skin mast cells also proved more susceptible than their uterine counterparts to lysis by the detergents, Triton X-100 and Tween 20, suggesting that fundamental differences in membrane structure and/or fluidity might account for functional heterogeneity within the human mast cell population.

Amino Acids↗
PubMed1990

[Antigenicity and allergenicity of hypoallergenic hydrolysate for infant nutrition].

The antigenicity/allergenicity of protein components in hypoallergenic formulae is altered by hydrolysis. Two different hydrolysate formulae, hydrolysate 1 = cow milk based; hydrolysate 2 = soya/beef collagen based, were investigated with respect to their specific IgG/IgE binding capacities using the sera of 41 healthy controls, 40 atopic and 12 cow milk allergic subjects. Furthermore, histamine liberation from basophils on incubation with milk proteins and the hydrolysates was measured in 5 healthy and 3 cow milk allergic individuals. Nearly all probands demonstrated specific IgG binding with hypoallergenic formulae. Anti-hydrolysate 1 IgG titres were higher than titres against hydrolysate 2 in the cow milk allergic and healthy populations. Nonhydrolyzed cow milk elicited IgE binding in all cow milk allergic sera. IgE-antibody for hydrolysate 2 could only be demonstrated in one atopic subject. Hydrolysate 1 showed binding capacity for the IgE-antibody of one atopic and 3/12 cow milk allergic patients. Histamine liberation followed in-vitro incubation with both hydrolysates in one out of 3 cow milk allergic subjects and two out of these cases following incubation to unprocessed cow milk protein. A decreased antigenicity/allergenicity can be demonstrated for the two hydrolysates investigated, however antigenic/allergenic reactivity is still present to some degree. Therefore, the therapeutic application of hypoallergenic formulae in patients with specific sensitization to cow milk should be based on the results of the above-mentioned in-vitro parameters and if necessary skin tests and oral challenges.

Adolescent↗
PubMed1984

The effect of compound 48/80 on the precipitated withdrawal syndrome of dogs.

The aim of this study was to eliminate endogenous stores of histamine before inducing the precipitated withdrawal syndrome. Results demonstrate that histamine plays a role in the emergence of some of the symptoms which characterize the precipitated abstinence syndrome in morphine-dependent dogs. Morphine-dependent dogs receiving 0.5 mg/kg n-allyl-normorphine exhibit the precipitated abstinence syndrome. Injection of compound 48/80, 0.5 mg/kg, a potent histamine liberator, produced, on the other hand, typical signs of the abstinence syndrome. A second injection of this compound 24 hours later, however, failed to induce these signs. An injection of n-allyl-normorphine also failed to induce these signs in dogs pretreated with compound 48/80 despite the fact that the dogs were still on their morphine regime. Control experiments on naive animals showed that injection of 0.5 mg/kg n-allyl-normorphine failed to produce signs of the abstinence syndrome. Injection of compound 48/80, a potent histamine liberator, on the other hand, did produce the typical signs of the abstinence syndrome. Animals pretreated with n-allyl-normorphine followed by compound 48/80 responded similarly to animals treated with compound 48/80 alone.

Animals↗
PubMed2004

Pharmacodynamics and pharmacokinetics of high-dose oxycodone infusion during and after coronary artery bypass grafting.

OBJECTIVE: In small to moderate doses, oxycodone has similar analgesic efficacy to morphine with fewer side effects. The present study evaluated the pharmacokinetics and dynamics of high doses of oxycodone during anesthesia for primary coronary artery bypass grafting. DESIGN: A randomized, prospective clinical evaluation. SETTING: A major Scandinavian university clinic. PARTICIPANTS: Two groups with 10 patients each were studied. INTERVENTIONS: Invasive hemodynamics, echocardiograms, and electrocardiograms were monitored. Oxycodone kinetics, histamine liberation, and plasma cortisol levels were measured. Anesthesia was induced with 1.0 mg/kg of oxycodone and, thereafter, in a random order, maintained with a continuous infusion of oxycodone at a rate of either 0.5 mg/kg/h (group OX 0.5, 10 patients) or 1.0 mg/kg/h (group OX 1.0, 10 patients). An additional bolus dose of 0.5 mg/kg (OX 0.5) or 1.0 mg/kg (OX 1.0) of oxycodone was given before the incision. Enflurane was administered according to hemodynamic criteria. MEASUREMENTS AND MAIN RESULTS: The induction of and the course of anesthesia were hemodynamically stable in all patients. Enflurane was given to every patient. The mean total doses of oxycodone were 3.5 mg/kg (OX 0.5) and 6.2 mg/kg (OX 1.0). The median t(1/2) of oxycodone varied from 5.1 to 5.9 hours. No hemodynamic differences were found between the groups. No histamine liberation was detected. During anesthesia, the predominant waves in the EEG were theta;- and delta-waves. The mean times to awakening were 3.8 hours and 7.0 hours in the groups OX 0.5 and 1.0, respectively. All patients were intubated until the first postoperative morning. No recall of awareness was reported. CONCLUSION: A combination of oxycodone and enflurane provides hemodynamically stable anesthesia. No advantages were gained with the higher dose. Elimination of oxycodone was slower than reported previously.

Analgesics, Opioid↗
PubMed1976

Cytophilic antibodies in bronchopulmonary aspergilloma and cryptogenic pulmonary eosinophilia.

The immunoglobulin class and subclass of cytophilic antibodies have been studied using peripheral leucocytes from twenty-two patients with allergic bronchopulmonary aspergillosis, aspergilloma and cryptogenic pulmonary eosinophilia. In patients with allergic bronchopulmonary aspergillosis, significantly increased histamine liberation occurred following challenge of their leucocytes with antisera to IgE, IgG2, IgG3 and IgG4 as well as with Aspergillus fumigatus antigen. The results were considerably modified if the patient was receiving corticosteroids at the time of the test. The presence of IgG2-specific antibody to A. fumigatus in the serum of one patient, capable of sensitizing donor leucocytes, was demonstrated in passive sensitization experiments. In two patients with uncomplicated aspergillomas no evidence of cytophilic antibody to any class was found although large amounts of precipitating IgG antibody was present in the serum. Two patients with aspergilloma and systemic symptoms of weight loss and fatigue (which have been interpreted by others as 'hypersensitivity' responses) had increased amounts of cytophilic antibody similar to those with allergic bronchopulmonary aspergillosis. Six patients with cryptogenic pulmonary eosinophilia were also studied. No evidence of specific antibody to A. fumigatus was found but, as a group, significantly increased histamine liberation using antisera to IgG2 was demonstrated. Individual patients also showed evidence of other classes of cytophilic antibody, one having IgE, three IgG3 and two IgG4. The relationship between heat-stable short-term sensitizing antibody (IgG STS) inducing immediate skin responses and the pattern of cytophilic antibodies found in our patients with bronchopulmonary aspergillosis having dual (immediate and late reactions) is discussed. Clinically these tests are of diagnostic value and they may be helpful in assessing symptomatic patients with aspergillomas for corticosteroid treatment.

Adult↗
PubMed1979

Liberation of histamine by compound 48/80, tolazoline, betahistine and burimamide from isolated spontaneously beating guinea pig and rabbit atrial pairs.

Tolazoline, betahistine, burimamide and compound 48/80 release histamine from isolated guinea pig atria resulting in histamine concentrations that stimulate H2-receptors. Tolazoline, burimamide and 48/80 also release histamine from rabbit atria but do not result in histamine concentrations that will stimulate either H1- or H2-receptors. However, betahistine (which does not release histamine from rabbit atria) and tolazoline stimulate the rabbit atrial chronotropic response by releasing catecholamines.

Animals↗
PubMed1987

Alterations in histamine levels in the rat induced by compound 48/80.

Histamine release in the rat was induced in vivo either by a single dose of compound 48/80 injected i.v. or by four repeated, daily doses of the same compound injected i.p. After i.v. injection the levels of blood histamine were determined and after i.p. injections the changes in both tele-methylhistamine and histamine levels in different tissues were investigated. I.v. injection of 48/80 induced a very rapid and marked increase of blood histamine by 7.4 to 11-fold over the control levels within the first two minutes. After repeated i.p. injections of compound 48/80 most tissues showed higher than normal tele-methylhistamine/histamine ratios. The results suggest that agents known to induce release of histamine from mast cells may exert significant changes in blood and tissue histamine levels and that liberated histamine is thereafter extensively catabolized.

Animals↗