Heat shock proteins in human and mouse embryonic cells after exposure to heat shock or teratogenic agents.

In human chorionic villus tissue at the 10-17th week of a normal pregnancy, heat shock proteins (hsp70, hsp73, hsp85, and hsp105) were induced in vitro by a heat shock or by exposure to sodium arsenite or cadmium chloride. In dispersed cells of the whole mouse embryo on the 11th day of development, heat shock proteins (hsp73 and hsp105) were induced by a heat shock or by exposure to sodium arsenite, but not by exposure to cadmium chloride. After a maternal hyperthermia or an intraperitoneal injection of sodium arsenite or cadmium chloride into a pregnant mouse, heat shock proteins accumulated in the embryo on the 9th day of development, especially in the neuroepithelial tissue. The significance of heat shock proteins in the embryo is discussed.     

Abolition of anaphylactic shock by solanum lyratum Thunb

We investigated the effects of the aqueous extract of Solanum lyratum Thunb. (Solanaceae) (SLAE) on the anaphylactic reactions. SLAE inhibited compound 48/80-induced anaphylactic shock 100% with a dose of 1.0 mg/g body weight (BW) . When SLAE was pretreated at concentration ranging from 0.0001–1.0 mg/g BW, the serum histamine levels were reduced in a dose-dependent manner. Passive cutaneous anaphylaxis also inhibited to 69.3% by oral administration of SLAE (0.05 mg/g BW) . Moreover, SLAE dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80. The level of cAMP in RPMC, when SLAE was added, significantly increased compared with that of normal control. These results indicate that SLAE possess strong antianaphylactic activity.     

Inhibitory effect of anaphylactic shock by caffeine in rats

Caffeine is known to reduce evoked histamine secretion, but the effects of caffeine on anaphylactic shock have not been clarified. We have investigated the effects of caffeine on anaphylactic shock in rats. Systemic anaphylactic shock by compound 48/80 injection was monitored for 1 h. An IgE-dependent local anaphylactic shock was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. Caffeine inhibited compound 48/80-induced anaphylatic shock to 40% with a dose of 1 mg/kg. Caffeine (0.1 mg/kg) inhibited to 56.4+/-0.4% passive cutaneous anaphylactic shock activated by anti-DNP IgE. Caffeine (5-20 mM) significantly inhibited histamine release from rat peritoneal mast cells (RPMCs) activated by compound 48/80 or anti-DNP IgE. Especially, caffeine (20 mM) inhibited by 96.7+/-0.5% histamine release activated by compound 48/80. Moreover, caffeine (1-20 mM) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMCs. The level of cAMP in RPMCs, when caffeine (20 mM) was added, increased significantly after 5-60 min compared with that of a normal control. These results indicate that caffeine inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in vivo and in vitro.     

Release of leukotrienes and histamine by the isolated anaphylactic heart

The purpose of this study was to demonstrate the ability of heart tissue to release the mediators of anaphylaxis after antigenic challenges. Guinea pigs were sensitized with ovalbumin. Hearts were excised, perfused in a langendorff apparatus, and challenged with a bolus injection of ovalbumin. Analysis of the perfusates demonstrated the presence of histamine as determined by radioenzymatic assay. Histamine release was observed to be maximum after 2 min (8 +/- 1 nmol) of perfusion, then decreased to baseline level. The heart also released LTB4, LTC4, LTD4, and LTE4 as determined by high performance liquid chromatography and bioassays. The release of LTC4 occurred rapidly, reaching maximum after 2 min (4.2 +/- 1 pmol) and then returned to baseline level. Although the release of LTD4 paralleled the release of LTC4, it reached a maximum after 5 min (7.7 +/- 2 pmol). LTE4 was detected after 10 min and was undetectable after 15 min. Maximum release of LTB4 was observed after 5-10 min (15 +/- 3 pmol) and was no longer detectable after 15 min. These results indicate that the isolated sensitized heart undergoing antigenic challenge releases leukotrienes and histamine suggesting the cardiac anaphylaxis might occur by the locally released mediators.     

Inhibition of anaphylactic shock by gadolinium chloride-induced Kupffer cell blockade

Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study, the effect of macrophage blockade induced by gadolinium chloride (GdCl₃) on anaphylactic shock is investigated. Our observations show that GdCl₃ prevents lethal anaphylactic shock in mice sensitized to ovalbumin. Gadolinium chloride given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 80% survival, compared with the 43% survival in the control group. The same dose of this rare-earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containingBordetella pertussis vaccine, and similarly abrogated the symptoms of anaphylaxis, including the accumulation of serotonin and histamine in the liver. The results suggest that macrophages play an important role in mouse anaphylaxis.

     

Inhibition of anaphylactic shock by gadolinium chloride-induced Kupffer cell blockade

Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study, the effect of macrophage blockade induced by gadolinium chloride (GdCl₃) on anaphylactic shock is investigated. Our observations show that GdCl₃ prevents lethal anaphylactic shock in mice sensitized to ovalbumin. Gadolinium chloride given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 80% survival, compared with the 43% survival in the control group. The same dose of this rare-earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containingBordetella pertussis vaccine, and similarly abrogated the symptoms of anaphylaxis, including the accumulation of serotonin and histamine in the liver. The results suggest that macrophages play an important role in mouse anaphylaxis.     

Role of nitric oxide in anaphylactic shock

Nitric oxide, synthesized from the guanidino group ofl-arginine by nitric oxide synthase, has an important role in pathophysiological changes associated with anaphylaxis. Nitric oxide production due to activation of constitutive nitric oxide synthase is detected using a nitric oxide-selective electrode in anaphylactic rabbitsin vivo. A nitric oxide synthase inhibitor attenuates hypotension and hemoconcentration and decreases venous return but does not improve cardiac depression. Nitric oxide functionally antagonizes the effects of vasoconstrictors released by anaphylaxisin vitro. In animals pretreated with a nitric oxide synthase inhibitor, the cardiac output falls significantly, although venous return is increased. Pulmonary resistance is significantly increased with a nitric oxide synthase inhibitor, andl-arginine attenuates the bronchospasm. These findings suggest that production of nitric oxide may reduce the pathophysiologic changes, except for vasodilatation, associated with anaphylaxis.     

Suppression of anaphylactic shock in sensitized guinea pigs by cytochalasin B

Twenty-three guinea pigs, presensitized with horse serum, were injected intracardially with 1 ml of 1.5 X 10(-4) M cytochalasin B in a 2.5% dimethyl sulfoxide solution, 1.5 h before being challenged with the serum. Eighteen of the guinea pigs (80%) survived. A single intracardiac injection of cytochalasin B to the control group of guinea pigs at 1.5 h before administration of the allergen did not prevent their sensitization and death following challenge.     

Mechanisms and management of anaphylactic shock not responding to traditional therapy

Anaphylaxis results from the generation and release of a variety of mediators and their effects on various organs. Involvement of the respiratory and cardiovascular systems is of primary importance to the attending physician. Prompt recognition and initial therapy directed to maintenance of an effective airway and circulatory system is critical. Cardiovascular collapse may involve the parallel operation of several mechanisms including hypovolemia, alterations in pulmonary or systemic vascular resistance, depressed myocardial contractility, dysrhythmias, and exogenous drug administration. Although epinephrine is the mainstay of therapy, improvement in cardiovascular status may require aggressive fluid administration, and additional pharmacologic and non-pharmacologic aids.