scholarly journals THE MECHANISM OF ACTION OF CORTISONE IN EXPERIMENTAL HYPERSENSITIVITY

1953 ◽  
Vol 98 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Frederick G. Germuth
Keyword(s):  
Intravenous Injection ◽  
Mechanism Of Action ◽  
Antibody Production ◽  
Inhibitory Effect ◽  
Serum Sickness ◽  
Bovine Albumin ◽  
Renal Lesions ◽  
Granulomatous Lesions ◽  
Antigen Antibody ◽  
Circulating Antibody

Cortisone markedly suppressed the cardiovascular and renal lesions of serum sickness type hypersensitivity which ordinarily develop following the intravenous injection of bovine albumin. The inhibitory effect of cortisone on the allergic granulomatous lesions of the spleen was less striking; the lesions were less extensive, but the percentage of animals affected was unchanged. Cortisone in the dosage employed had no effect on the elimination of antigen following its intravenous administration or on the appearance of circulating antibody. These findings indicate that inhibition of the lesions of serum sickness by cortisone does not depend on the suppression of antibody production. Therefore, it is inferred that cortisone somehow protects the animal from the damaging effects of antigen-antibody union.

scholarly journals COMPARATIVE HISTOLOGIC AND IMMUNOLOGIC STUDIES IN RABBITS OF INDUCED HYPERSENSITIVITY OF THE SERUM SICKNESS TYPE

1955 ◽  
Vol 101 (2) ◽  
pp. 135-150 ◽  
Author(s):  
Frederick G. Germuth ◽  
Mary Geraldine Pace ◽  
Jack C. Tippett
Keyword(s):  
Intravenous Administration ◽  
Temporal Relationship ◽  
Serum Sickness ◽  
Foreign Protein ◽  
Bovine Albumin ◽  
Egg Albumin ◽  
Peak Incidence ◽  
Qualitative And Quantitative ◽  
Tissue Alteration ◽  
Antigen Antibody

Sensitization of rabbits with bovine albumin and the cross-reactive antigen, egg albumin, increased the rate of bovine albumin elimination following its intravenous administration. Elimination of this antigen was complete in 7 and 10 days respectively instead of approximately 2 weeks as in unsensitized normal animals. The peak incidence of allergic tissue alteration was proportionately accelerated. Certain qualitative and quantitative differences between the histologic responses of the sensitized and unsensitized rabbits were noted. These differences were probably due to the shorter period of antigen-antibody interaction in the sensitized animals in which the antigen was quickly eliminated. The temporal relationship between the histologic and immunologic responses in sensitized animals adds further support to the hypothesis that the lesions which occur after the injection of foreign protein are the result of antigen-antibody combination.

scholarly journals ELECTRON MICROSCOPY OF SERUM SICKNESS NEPHRITIS

1958 ◽  
Vol 108 (6) ◽  
pp. 957-962 ◽  
Author(s):  
Joseph D. Feldman
Keyword(s):  
Electron Microscopy ◽  
Endothelial Cells ◽  
Basement Membrane ◽  
Serum Sickness ◽  
Primary Reaction ◽  
Electron Dense Material ◽  
Renal Lesions ◽  
Microscopic Studies ◽  
Antigen Antibody ◽  
Serum Sickness Nephritis

The renal lesions of serum sickness were studied with the electron microscope. The most prominent change was a marked swelling and proliferation of glomernlar endothelial cells causing obliteration of the capillary lumen. The basement membrane also showed focal thickenings and excrescences. Deposits of electron-dense material blended into the basement membrane. On the extracapillary side epithelial foot processes were reduced in number and replaced by broad sheets of cytoplasm which were closely applied to the basement membrane. From a comparison of electron and fluorescent microscopic studies of the glomerulus in serum sickness, it would seem that antigen-antibody complexes initiated injury in endothelial cells, although the possibility of the primary reaction occurring on basement membrane cannot be excluded.

scholarly journals BARTONELLA BODIES IN THE BLOOD OF A NON-SPLENECTOMIZED DOG

1935 ◽  
Vol 62 (3) ◽  
pp. 353-258 ◽  
Author(s):  
James B. McNaught ◽  
Francis M. Woods ◽  
Virgil Scott
Keyword(s):  
Intravenous Injection ◽  
Plasma Protein ◽  
Whole Blood ◽  
Protein Level ◽  
Plasma Proteins ◽  
Basal Diet ◽  
Blood Stream ◽  
Inhibitory Effect ◽  
The Many ◽  
Plasma Protein Level

A non-splenectomized dog, on a vitamin-adequate basal diet, in the course of a plasmapheresis experiment, developed an uncontrollable anemia associated with the presence of bodies in or on the erythrocytes, indistinguishable from the descriptions of Bartonella canis. The normal plasma protein level of 7.3 per cent was reduced to 4.1 per cent by diet and the removal of 5354 ml. of whole blood in 33 bleedings. The Bartonella infection was transferred to a splenectomized dog by an intravenous injection of whole blood. Each animal was apparently sterilized by one injection of neoarsphenamine equivalent to 15 mg. per kilo weight. It is possible that the spleen liberates some substance into the blood stream which has an inhibitory effect upon a latent Bartonella infection and that this protective substance was diminished by the many bleedings associated with the lowering of plasma proteins in the non-splenectomized dog and was lacking in the inoculated splenectomized dog.

A novel triazolic naphthofuranquinone induces autophagy in reservosomes and impairment of mitosis in Trypanosoma cruzi

Parasitology ◽  
2011 ◽  
Vol 139 (1) ◽  
pp. 26-36 ◽  
Author(s):  
M. C. FERNANDES ◽  
E. N. DA SILVA ◽  
A. V. PINTO ◽  
S. L. DE CASTRO ◽  
R. F. S. MENNA-BARRETO
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Mechanism Of Action ◽  
Folk Medicine ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Membrane Structures ◽  
Starting Point ◽  
Nitro Derivatives ◽  
Good Starting Point

SUMMARYChagas' disease, caused by the protozoan Trypanosoma cruzi, represents a serious health problem in Latin America, and the available chemotherapy, which is based on 2 nitro-derivatives, is not satisfactory. In folk medicine, natural products including naphthoquinones have been employed for the treatment of different parasitic diseases. In the pursuit of alternative drugs for Chagas' disease, we investigated the mechanism of action of the triazolic naphthoquinone (TN; 2,2-dimethyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydronaphtho[1,2-b]furan-4,5-dione), which is the most active compound against T. cruzi trypomastigotes among a series of naphthofuranquinones. TN was active against the 3 parasite forms producing a dose-dependent inhibitory effect. In epimastigotes, TN induced reservosome disruption, flagellar blebbing, Golgi disorganization, the presence of cytosolic concentric membrane structures and abnormal multiflagellar parasites. The treatment also led to the appearance of well-developed endoplasmic reticulum profiles surrounding organelles that associated with an increase in monodansylcadaverine labelling, suggesting autophagy as part of the TN mechanism of action. Interestingly, no ultrastructural damage was detected in the mitochondria of naphthoquinone-treated epimastigotes. Flow cytometric analysis demonstrated an impairment of mitosis, an increase in ROS production and the maintenance of mitochondrial membrane potential. TN could be a good starting point in the investigation of a chemotherapeutic approach for the treatment of Chagas' disease.

Studies on the Mechanism of Action of the Inhibitory Effect of the Somatostatin Analog SMS 201–995 on the Growth of the Prolactin/Adrenocorticotropin-Secreting Pituitary Tumor 7315a

Endocrinology ◽  
1986 ◽  
Vol 118 (6) ◽  
pp. 2188-2194 ◽  
Author(s):  
STEVEN W. J. LAMBERTS ◽  
JEAN-CLAUDE REUBI ◽  
PIET UITERLINDEN ◽  
JOKE ZUIDERWIJK ◽  
PAUL VAN DEN WERFF ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Pituitary Tumor ◽  
Inhibitory Effect ◽  
Somatostatin Analog

Immunological Studies of Catechol Methyltransferase from the Yeast Candida tropicalis

1980 ◽  
Vol 35 (9-10) ◽  
pp. 712-716 ◽  
Author(s):  
Joseph Veser ◽  
Helmut Thomas
Keyword(s):  
Candida Tropicalis ◽  
Specific Antigen ◽  
Double Diffusion ◽  
Bovine Liver ◽  
Inhibitory Effect ◽  
Cross Reactivity ◽  
Diffusion Analysis ◽  
Potent Inhibitory Effect ◽  
Catechol Methyltransferase ◽  
Antigen Antibody

Abstract Immunization of rabbits with purified catechol methyltransferase from Candida tropicalis yielded a potent antiserum. Ouchterlony double diffusion analysis showed a single precipitin line. There was no cross reactivity with the catechol methyltransferase from rat and bovine liver. Specific antigen-antibody interaction was demonstrated by a potent inhibitory effect of the antibody on the yeast enzyme. Immunological titration and quantitative precipitin reaction of the enzyme showed that the maximum amount of precipitable complex occurred at the equivalence point where enzyme activity was completely inhibited.

Injury And Inflammation Induced In The Microcirculation Of The Rabbit By Antigen-Antibody Complexes

1981 ◽  
Author(s):  
J P Crawford ◽  
H Z Movat ◽  
N S Ranadive ◽  
J B Hay
Keyword(s):  
Blood Flow ◽  
Inflammatory Response ◽  
Skin Lesions ◽  
Precipitin Test ◽  
Cork Borer ◽  
Pulmonary Microcirculation ◽  
Antigen Antibody ◽  
Kinetics Of ◽  
Increased Blood Flow ◽  
Circulating Antibody

An experimental model was used to study the morphogenesis, quantitation and kinetics of the inflammatory response in the dermis of rabbits. New Zealand White rabbits were immunized with ovalbumin, bled, the antibody precipitated by ammonium sulphate and redissolved in saline. Circulating antibody was determined by the quantitative precipitin test. The reversed passive Arthus reaction was elicited by injecting normal rabbits intravenously with antigen [1.0 gm] and intradermally with 0.9 mg of antibody, in triplicate sites. The lesions were allowed to develop for 1-8, 18 and 24 hours post-injection. To assess the inflammatory response, 5 parameters were examined: 1) Exudation of plasma using 125I-serum albumin; 2) Infiltration of leukocytes with 51Cr-labelled cells; 3) Hemorrhage with 59Fe-erythrocytes; 4) Formation of microthrombi with 111In-platelets; and 5) Blood flow with 57Co-microspheres. The animals were killed, the lesions punched out with a cork borer and counted in a gamma spectrometer. Skin lesions from rabbits not injected with tracers were fixed in glutaraldehyde-formalin and prepared for microscopic examination. With the aid of these techniques, increase of vascular permeability and the formation of microthrombi peaked in 2-hour old lesions. Increased blood flow peaked in leasions 3-4 hours postinjection. Infiltration of polymorphonuclear leukocytes reached a maximum in lesions 2-3 hours old, followed by hemorrhage, which reached a maximum and plateaued after 4 hours. Immune complexes may induce a hemorrhagic inflammation, the kinetics of which can be ascertained. Preliminary studies indicate that these techniques are applicable for the examination of experimentally-induced hypersensitivity pneumonitides and disorders of the pulmonary microcirculation.

Uncoupling of Lipolysis from Cyclic AMP by Procaine: a Tool for Studying the Mechanism of Action of Antilipolytic Agents

1975 ◽  
Vol 53 (4) ◽  
pp. 603-609 ◽  
Author(s):  
Mario D'Costa ◽  
Aubie Angel
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Mechanism Of Action ◽  
Initial Rate ◽  
Direct Action ◽  
Inhibitory Effect ◽  
Glycerol Release ◽  
Cyclic Amp Accumulation ◽  
Low K

The initial rate of net glycerol release in norepinephrine-stimulated adipose tissue fragments was inhibited (40–78%) by procaine–HCl (1–5 mM), whereas basal (unstimulated) lipolysis was unaffected. A dose-related inhibition of norepinephrine-induced lipolysis by procaine–HCl (0.1–1 mM) also occurred in adipocytes. Procaine-induced antilipolysis was associated with an augmented rather than a reduced hormone-stimulated increment in intracellular cyclic AMP. The dissociation of lipolysis from cyclic AMP accumulation has been termed the uncoupling effect of procaine. This effect of procaine was employed to define the precise mechanism of action of the antilipolytic drug clofibrate (Atromid-S®) which inhibits lipolysis by reducing cyclic AMP. A reduction in cyclic AMP by clofibrate was demonstrated in norepinephrine-stimulated cells exposed to procaine (uncoupled system). Thus, the inhibitory effect of clofibrate on cyclic AMP could not be attributed to accumulation of products of lipolysis. Because neither procaine–HCl nor clofibrate had any effect on the low Km 3′:5′-cyclic-AMP phosphodiesterase (EC 3.1.4.17) activity in hormone stimulated cells, the clofibrate-induced reduction in cyclic AMP was attributed to its direct action on adipocyte adenylate cyclase.

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