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Inhibitions of the rat reaginic passive cutaneous anaphylaxis
10
J. ALLERGY
Abstracts
Pediatrics
Pharmacology, pathology
CLIN. IMMUNOL. MARCH 1979
physiology,
and
Abnormalities of in vitro lymphocyte response to mitogens in diabetic children during acute ketoacidosis
Inhibition of the rat reaginic cutaneous anaphylaxis
Speert, D. P., and Silva, J., Jr.: Am. J. Dis. Child. 132:1014, 1978.
Hurtado, I., Marquez, V., and Vitolo, M: Int. Arch. Allergy Appl. Immunol. 57:507, 1978.
Since patients with diabetes mellitus are more susceptible to unusual infections than are nondiabetic patients, and since these infections may be associated with depressed cell-mediated immunity, this study was undertaken to evaluate lymphocyte transformation and delayed hypersensitivity skin tests in children with diabetic ketoacidosis. The study group was comprised of 11 patients (10 to 17 yr) with juvenile-onset diabetes. Ten of them had been insulin-dependent for five or more years and 1 newly diagnosed with acute ketoacidosis; none had a history of frequent or unusual infections. Six patients (all female) hospitalized with ketoacidosis had multiple lymphocyte studies during their hospital stay (at the time of admission, 6 to 12 hr after treatment, and after 1 wk), and 5 had one study during episodes of mild ketonuria without acidosis. Lymphocyte transformations were performed by incubating small lymphocytes with phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), Candida albicans, purified protein derivative (PPD), staphylococcus toxoid, and tritiated thymidine. Delayed hypersensitivity skin tests were performed by the injection of 0.1 ml of PPD, C. albicans, streptokinase-streptodomase (SK-SD), histoplasmin, and Dermatophyton. Of the 6 patients with ketoacidosis, 5 had a positive skin test to Can&u and 3 of those also reacted to SK-SD. No patient responded to Dermatophyton, histoplasmin, or PPD, and 1 was unresponsive to all the antigens. Whereas the lymphocytes from patients with mild ketonuria responded normally to PWM, PHA, and Con A mitogens, those from patients with acute ketoacidosis were significantly depressed (3 were unresponsive to Con A and 2 to PHA and PWM). The mean lymphocyte responses of patients with ketoacidosis increased greatly to each mitogen 6 to 12 hr after therapy was initiated, and 1 wk later significantly exceeded the values for age-matched and laboratory controls. There was no consistent depression of lymphocyte transformation when normal lymphocytes were cultured with plasma from patients with acute ketoacidosis, nor was there consistent improvement when lymphocytes from patients with ketoacidosis were cultured with normal plasma. No changes in lymphocyte transformation to PHA, Con A, or PWM were observed when lymphocytes from control donors were cultured in autologous plasma with varying glucose concentrations (300, 500, and 700 mglml). The authors conclude that in vitro cell-mediated immunity is transiently defective in children with acute ketoacidosis, and they suggest that a transient abnormality in the lymphocyte membrane or its internal metabolism may explain this observation. s. B.
LC-6 (Trans-2, 3b, 4, 5, 7, 8b, 9, lo-Octahydronaphthol [ 1, 2-c:5, 6-c] Dipyrazole) is a newly synthesized chemical compound which, like disodium cromoglycate (DSCG), is capable of interacting with a potential receptor through hydrogen binding by means of its symmetrically spaced heterocyclic pyrazole rings. This capacity suggests the possibility that LC-6 could act in the same manner as DSCG in preventing mediator release from cells activated by an IgE-allergenic combination. In preliminary passive cutaneous anaphylaxis (PCA) experiments it was established that LC-6 failed to inhibit skin reactions to histamine or to the mediators released from rat mast cells by compound 48/80. LC-6 was then administered orally to rats and was found to inhibit the reaginic PCA reaction in a manner similar to that noted when DSCG was administered intravenously. The inhibition resulting from LC-6 was found to be long-lasting and dose-dependent. When the compound was administered in two successive doses the inhibition of PCA was often greater than after a single dose, showing that predosing with LC-6 does not cause desensitization, whereas a predose of DSCG interferes with reaction to the second dose. From these results it can be seen that LC-6 has a certain advantage over DSCG in that its inhibitory effect on PCA is longer lasting, that its effect is dose-related, that predosing increases its effectiveness, and that it can be administered orally. All of these characteristics make it a valuable tool in the search for receptors involved in the anaphylactic reaction. H. F.
passive
The relation of production formulation absorption of oral theophylline
to
Weinberger, M., Hendeles, L., and Bighley, N. Engl. J. Med. 299:852, 1978.
L.:
A group of 20 asthmatic subjects, aged 18 to 52, received 7.5 mg/kg of theophylline as a loading dose, followed by either a theophylline solution, plain uncoated or coated tablets, or several sustained-release preparations. The theophylline solution was found to be a rapid, reliable, and completely absorbed product. The fraction, rate, and completeness of absorption of the various products were measured. Absorption of uncoated tablets was not significantly different than for the solution. Absorption was delayed with coated tablets, such as Choledyl, which had a 2-hr lag before any measurable theophylline level was found. Three of 6 sustained-release formulations (Slo-phyllin Gyrocap, Theophylline S-R, Theo-Dur sustained-release tablet) were
J. ALLERGY
Abstracts
Pediatrics
Pharmacology, pathology
CLIN. IMMUNOL. MARCH 1979
physiology,
and
Abnormalities of in vitro lymphocyte response to mitogens in diabetic children during acute ketoacidosis
Inhibition of the rat reaginic cutaneous anaphylaxis
Speert, D. P., and Silva, J., Jr.: Am. J. Dis. Child. 132:1014, 1978.
Hurtado, I., Marquez, V., and Vitolo, M: Int. Arch. Allergy Appl. Immunol. 57:507, 1978.
Since patients with diabetes mellitus are more susceptible to unusual infections than are nondiabetic patients, and since these infections may be associated with depressed cell-mediated immunity, this study was undertaken to evaluate lymphocyte transformation and delayed hypersensitivity skin tests in children with diabetic ketoacidosis. The study group was comprised of 11 patients (10 to 17 yr) with juvenile-onset diabetes. Ten of them had been insulin-dependent for five or more years and 1 newly diagnosed with acute ketoacidosis; none had a history of frequent or unusual infections. Six patients (all female) hospitalized with ketoacidosis had multiple lymphocyte studies during their hospital stay (at the time of admission, 6 to 12 hr after treatment, and after 1 wk), and 5 had one study during episodes of mild ketonuria without acidosis. Lymphocyte transformations were performed by incubating small lymphocytes with phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), Candida albicans, purified protein derivative (PPD), staphylococcus toxoid, and tritiated thymidine. Delayed hypersensitivity skin tests were performed by the injection of 0.1 ml of PPD, C. albicans, streptokinase-streptodomase (SK-SD), histoplasmin, and Dermatophyton. Of the 6 patients with ketoacidosis, 5 had a positive skin test to Can&u and 3 of those also reacted to SK-SD. No patient responded to Dermatophyton, histoplasmin, or PPD, and 1 was unresponsive to all the antigens. Whereas the lymphocytes from patients with mild ketonuria responded normally to PWM, PHA, and Con A mitogens, those from patients with acute ketoacidosis were significantly depressed (3 were unresponsive to Con A and 2 to PHA and PWM). The mean lymphocyte responses of patients with ketoacidosis increased greatly to each mitogen 6 to 12 hr after therapy was initiated, and 1 wk later significantly exceeded the values for age-matched and laboratory controls. There was no consistent depression of lymphocyte transformation when normal lymphocytes were cultured with plasma from patients with acute ketoacidosis, nor was there consistent improvement when lymphocytes from patients with ketoacidosis were cultured with normal plasma. No changes in lymphocyte transformation to PHA, Con A, or PWM were observed when lymphocytes from control donors were cultured in autologous plasma with varying glucose concentrations (300, 500, and 700 mglml). The authors conclude that in vitro cell-mediated immunity is transiently defective in children with acute ketoacidosis, and they suggest that a transient abnormality in the lymphocyte membrane or its internal metabolism may explain this observation. s. B.
LC-6 (Trans-2, 3b, 4, 5, 7, 8b, 9, lo-Octahydronaphthol [ 1, 2-c:5, 6-c] Dipyrazole) is a newly synthesized chemical compound which, like disodium cromoglycate (DSCG), is capable of interacting with a potential receptor through hydrogen binding by means of its symmetrically spaced heterocyclic pyrazole rings. This capacity suggests the possibility that LC-6 could act in the same manner as DSCG in preventing mediator release from cells activated by an IgE-allergenic combination. In preliminary passive cutaneous anaphylaxis (PCA) experiments it was established that LC-6 failed to inhibit skin reactions to histamine or to the mediators released from rat mast cells by compound 48/80. LC-6 was then administered orally to rats and was found to inhibit the reaginic PCA reaction in a manner similar to that noted when DSCG was administered intravenously. The inhibition resulting from LC-6 was found to be long-lasting and dose-dependent. When the compound was administered in two successive doses the inhibition of PCA was often greater than after a single dose, showing that predosing with LC-6 does not cause desensitization, whereas a predose of DSCG interferes with reaction to the second dose. From these results it can be seen that LC-6 has a certain advantage over DSCG in that its inhibitory effect on PCA is longer lasting, that its effect is dose-related, that predosing increases its effectiveness, and that it can be administered orally. All of these characteristics make it a valuable tool in the search for receptors involved in the anaphylactic reaction. H. F.
passive
The relation of production formulation absorption of oral theophylline
to
Weinberger, M., Hendeles, L., and Bighley, N. Engl. J. Med. 299:852, 1978.
L.:
A group of 20 asthmatic subjects, aged 18 to 52, received 7.5 mg/kg of theophylline as a loading dose, followed by either a theophylline solution, plain uncoated or coated tablets, or several sustained-release preparations. The theophylline solution was found to be a rapid, reliable, and completely absorbed product. The fraction, rate, and completeness of absorption of the various products were measured. Absorption of uncoated tablets was not significantly different than for the solution. Absorption was delayed with coated tablets, such as Choledyl, which had a 2-hr lag before any measurable theophylline level was found. Three of 6 sustained-release formulations (Slo-phyllin Gyrocap, Theophylline S-R, Theo-Dur sustained-release tablet) were