Repeated recurrence of gastric mucosal lesions in rats after a single treatment with compound 48/80, a mast cell degranulator.

We examined the recurrence of gastric mucosal lesions in rats after a single treatment with compound 48/80 (C48/80), a mast cell degranulator. During the period of 0.5 h to 24 h after treatment with C 48/80 (0.75 mg/kg, i.p.), an apparent recurrence of gastric mucosal lesions was found 18 and 24 h after the lesion formation, progression, and recovery occurred during the period of 12 h. Gastric mucosal blood flow showed the maximum reduction at 0.5, 16, and 22 h after treatment followed by the maximum recovery of the decrease at 12, 20, and 24 h, respectively. Gastric mucosal myeloperoxide and xanthine oxidase activities and lipid peroxide content showed the maximum increase at 3, 18, and 24 h after treatment. Gastric mucosal superoxide dismutase activity unchanged after treatment and gastric mucosal catalase activity decreased only at 24 h. Gastric mucosal Se-glutathione peroxidase activity and vitamin E, ascorbic acid, and hexosamine contents showed their maximum decrease at 3, 18, and 24 h after treatment. Gastric mucosal non-protein SH content showed the maximum decrease at 0.5, 16, and 22 h after treatment. Serum histamine and serotonin concentrations increased rapidly after treatment but the increases in serum histamine and serotonin concentrations diminished completely until 12 and 14 h, respectively. These results indicate that lesions recur repeatedly accompanied with an ischemia-reperfusion-like change in blood flow, inflammation, and disruption of antioxidant defense systems in the gastric mucosa of rats in no relation to released histamine and serotonin after a single C48/80 treatment.

[Lymphocytes as markers of etiologic and pathogenetic factors of infectious diseases]. / Limfotsity--markery étiologicheskikh i patogeneticheskikh faktorov infektsionnoi patologii.

In the examination of patients with the dermato-respiratory syndrome, peptic ulcer, pyoderma and surgical wounds for their immune status for the expression of receptors of immunocytokins (interferon, interleukin-2), autocoids (histamine, serotonin), neuromediators (acetylcholine, dopamine, epinephrine, norepinephrine) and for the presence of Staphylococcus aureus and Helicobacter pylori antigens have revealed that lymphocytes are the markers of the presence of infection in the body, pathogenetic systemic and intersystemic disturbances, adequately chosen therapy and its effectiveness.

Histamine, tryptase, norepinephrine, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II in plasma of patients with hymenoptera venom anaphylaxis.

Markers of immediate-type hypersensitivity such as histamine and tryptase were measured in the plasma of nonallergic volunteers and patients with a history of hymenoptera venom anaphylaxis. No significant differences in histamine or tryptase were found between patients and controls. Norepinephrine, an important compound involved in the control of cardiovascular functions and blood pressure, was the same in patients and nonallergic volunteers. In addition, components of the renin-angiotensin system were determined. Patients with hymenoptera venom anaphylaxis showed significantly lower plasma angiotensinogen concentrations as compared to healthy nonallergic controls (p < 0.007), whereas plasma ACE activity was the same. Likewise, the plasma levels of angiotensin I and angiotensin II were significantly reduced in patients as compared to controls (p < 0.04 and p < 0.003, respectively). These findings suggest that the renin-angiotensin system may play an important role as a counteracting factor in hymenoptera venom anaphylaxis.

Simultaneous measurement of intestinal blood flow and plasma levels of vasoactive substances in a case of early dumping syndrome. Case report.

Increase in intestinal blood flow was observed in a patient with postprandial hypotension. Simultaneous measurement of hemodynamic parameters and plasma levels of gut hormones revealed that the release of various vasoactive substances and resulting vasodilation of abdominal organs were responsible for the vasomotor changes of early dumping syndrome.

Comparative effects of smooth and rough Pasteurella hemolytica lipopolysaccharides on arachidonic acid, eicosanoids, serotonin, and histamine in calves.

Effect of IV infusions of smooth and rough Pasteurella hemolytica lipopolysaccharides (LPS; 24 ng/kg/min for 500 min) on circulating levels of arachidonic acid, prostaglandins (PG), thromboxane B2 (TxB2), histamine, and serotonin in calves was evaluated. Both smooth and rough LPS had no effects on plasma PGE but caused maximal increases in arachidonic acid, TxB2, and PGF2 alpha at 1 hr and 6-keto-PGF1 alpha at 3 hr of infusion, respectively. The increases in arachidonic acid and its metabolites were greater and more prolonged for smooth LPS than for rough LPS. Although both rough and smooth LPS increased plasma serotonin transiently at 25 min of infusion, only rough LPS decreased serotonin in the later period of endotoxemia. In contrast, smooth, but not rough, LPS decreased plasma histamine during endotoxemia. These results indicate that during endotoxemia there is increased PG and TxA2 synthesis secondary to marked arachidonic acid release into circulation. The data also demonstrate that smooth and rough LPS differ in their abilities to release histamine, serotonin, and eicosanoids. These effects might be due to differences in the in vivo mechanisms of action of smooth and rough LPS and may partly explain the differential potency of smooth and rough LPS in producing pathophysiological changes.

Measuring leukotrienes of slow reacting substance of anaphylaxis: development of a specific radioimmunoassay.

Rabbits were immunized with leukotriene C4 (LTC4) coupled to thiolated keyhole limpet hemocyanin (KLH) by using 6-N-maleimidohexanoic acid as a spacer molecule. Immune serum was obtained with 7.9 nmol of LTC4-specific immunoglobulin per milliliter and a mean association constant of 2.1 X 10(9) M-1. A radioimmunoassay was developed that detected 0.1 pmol of LTC4 per 1-ml sample. LTD4 and LTE4, three isomers of LTC4, the sulfones of LTC4, LTD4, and LTE4, and one isomer of LTD4 reacted to varying degrees in the assay. A number of other structurally related compounds, such as LTB4 and 5-HETE, did not react. Conditions were established to determine LTC4 levels in human plasma without loss of LTC4 during sample preparation and without the need for extraction procedures before the measurement of LTC4.

Effect of the Ca2+ antagonist nifedipine on the release of platelet-activating factor (PAF-acether), slow-reacting substance and beta-glucuronidase from human neutrophils.

Ca2+ antagonists such as nifedipine (Nif) inhibit processes that depend on extracellular Ca2+ in many muscular and secretory cells. The effect of Nif on mediator release and Ca2+ uptake by human polymorphonuclear neutrophils (PMN) has been investigated. Nif caused a concentration-dependent inhibition of the Ca2+ ionophore-induced release of platelet-activating factor (PAF-acether), slow-reacting substance (SRS) and to a lesser degree beta-glucuronidase (beta-glu). Nif inhibited the synthesis of PAF-acether rather than its release. Increasing Ca2+ concentration in the bathing medium from 1.3 to 2.8 mM completely reversed the effect of Nif on PAF-acether secretion. Nif at 1 and 5 microM reduced PMN45Ca2+ uptake induced by the Ca2+ ionophore A 23187. These results indicate that the inhibition by Nif of mediator release depends probably on the Ca2+-antagonistic property of the drug. A preliminary ex vivo study suggests that this inhibitory effect on neutrophil functions exists during therapeutic use.

Characterization of slow reacting substances (SRSs) of rat basophilic leukemia (RBL-1) cells: effect of cysteine on SRS profile.

When RBL-1 cells were incubated with L-cysteine (7.5 mM) and the ionophore A23187, the slow reacting substances SRS-GSH and SRS-Cys-Gly were formed. When L-cysteine was omitted in the incubation, SRS-GSH and SRS-Cys were isolated but only a trace amount of SRS-Cys-Gly was detectable. Each of the characterized SRSs was accompanied by an as yet uncharacterized structural isomer showing UV absorption at 278 nm. L-Cysteine and other thiols inhibited an aminopeptidase that transforms the highly bioactive SRS of anaphylaxis (SRS-Cys-Gly) into the less bioactive SRS-Cys. SRS-GSH, SRS-Cys-Gly, and SRS-Cys may be readily distinguished from each other by means of their bioactivities, antagonism by FPL 55712, and relative susceptibilities to the actions of soybean lipoxygenase, microsome-bound leucine aminopeptidase, and gamma-glutamyl transpeptidase.

Characterization of the two major species of slow reacting substance from rat basophilic leukemia cells as glutathionyl thioethers of eicosatetraenoic acids oxygenated at the 5 position. Evidence that peroxy groups are present and important for spasmogenic activity.

The most prominent slow reacting substance from rat basophilic leukemia cells (type I) was characterized by radiochemical, chemical and physical methods and shown to contain a C20 unsaturated fatty acid oxygenated at the 5 position and a sulfur containing side chain in thioether linkage at the 6 position. Its spasmogenic action on guinea pig ileal muscle was largely inactivated under reducing conditions which suggested that a peroxy group was present and important for contractile activity. This was supported by ferrous thiocyanate analysis. The peroxy group is almost certainly at the 5 position, probably in the form of a peroxy ester or hydroperoxide. Based on amino acid hydrolysis (0.85 moles of glycine and 0.30 moles of glutamic acid per mole SRS), the sulfur containing side chain is apparently a mixture of glutathione and cysteinyl-glycine, but by chromatography the side chain is predominantly glutathione and the low yield of glutamic acid may be due to complexing of its alpha COOH group in a peroxy ester linkage. The fatty acid moiety has 3 conjugated double bonds, probably at the 7,8, 9,10 and 11,12 positions. Type II SRS, the second major species, differs in that the sulfur containing side chain is linked at the 12 or 13 position and is almost certainly glutathione and in the failure of alkaline borohydride to produce inactivation. These observations strongly implicate the lipoxygenase pathway in slow reacting substance biosynthesis.

Airway sensitivity to slow-reacting substance of anaphylaxis, histamine, and antigen in Ascaris sensitive monkeys.

The effects of Ascaris suum antigen, histamine, and slow-reacting substance of anaphylaxis (SRS-A) on the respiratory system were compared in 3 anesthetized rhesus monkeys. The agents were administered by instillation into the trachea, and the animals were studied in a volume displacement body plethysmograph. Two of the animals showed skin and bronchial sensitivity to Ascaris suum antigen and responded to it with increased pulmonary resistance and decreased dynamic compliance. A similar response was seen in all 3 animals after instillation of histamine, but SRS-A at 2 concentrations produced a predominant effect of decreased dynamic compliance with lesser alterations in pulmonary resistance. The effects of SRS-A were slow in onset and prolonged, as compared to the abrupt and short-lived effects of Ascaris suum antigen and histamine. The predominant effect of SRS-A on dynamic compliance suggests a more peripheral site of action of this mediator. In 5 monkeys allergic to Ascaris, no SRS-A could be detected in the blood at one and 5 min after antigen challenge, using the bioassay techniques.