scholarly journals STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES

1953 ◽  
Vol 98 (4) ◽  
pp. 331-348 ◽  
Author(s):  
Morgan Berthrong ◽  
Leighton E. Cluff
Keyword(s):  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Buffy Coat ◽  
Single Intravenous Injection ◽  
Bacterial Endotoxins ◽  
Leucocyte Migration ◽  
Shwartzman Reaction ◽  
Local Shwartzman Reaction

Intravenous injection into rabbits of bacterial endotoxins results in an inhibition of migration of leucocytes from the buffy coat of their blood in tissue culture or in "slide cell" preparations. This effect was demonstrable 5 minutes after the intravenous injection and persisted for from 6 to 12 hours after the injection. It is as marked in rabbits receiving only a single intravenous injection of endotoxin as in those previously prepared intradermally and developing a severe local Shwartzman reaction on intravenous injection. The preparation of the skin for the Shwartzman reaction does not in itself result in appreciable changes of leucocyte migration. The production of the effect depends upon some action in vivo, since leucocytes of uninjected rabbits migrate normally from the buffy coat in plasma substrates to which large concentrations of endotoxin are added in vitro. The inhibitory effect, as observed in these experiments, also depends upon the added influence of centrifugation. Leucocytes from a rabbit receiving endotoxin intravenously migrate normally from uncentrifuged lung or spleen fragments and migrate normally in blood on the warm stage prior to centrifugation. Identical centrifugation does not affect leucocytes from uninjected animals. The heparin inhibition of the local Shwartzman reaction does not alter this effect of endotoxins on leucocytes. Its possible role in the production of leucopenia and of the local Shwartzman reaction is briefly discussed.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1952 ◽  
Vol 96 (6) ◽  
pp. 625-641 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Trypan Blue ◽  
Nitrogen Mustard ◽  
Skin Lesions ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Single Intravenous Injection ◽  
Shwartzman Reaction ◽  
Kidney Lesions ◽  
Local Shwartzman Reaction

Intravenous injection of thorotrast or trypan blue rendered rabbits susceptible to the production of bilateral cortical necrosis of the kidneys by a single intravenous injection of small amounts of meningococcal or Serratia marcescens toxin. This reaction was not produced when thorotrast or trypan blue were injected after toxin had been given. A single intradermal injection of toxin produced hemorrhagic skin lesions resembling the local Shwartzman reaction in rabbits given thorotrast 6 hours previously. These animals also developed bilateral cortical necrosis of the kidneys. When the order of injection was reversed, and thorotrast given after toxin, neither skin nor kidney lesions occurred. The skin and kidney lesions in thorotrast-treated rabbits were, like the local and generalized Shwartzman reactions, completely prevented by treatment with nitrogen mustard, in doses sufficient to produce polymorphonuclear leukopenia. The significance of these reactions, and their relationship to the previously described response to toxin in cortisone-treated rabbits, are discussed.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER

1957 ◽  
Vol 106 (6) ◽  
pp. 787-809 ◽  
Author(s):  
Robert G. Petersdorf ◽  
Willis R. Keene ◽  
Ivan L. Bennett
Keyword(s):  
Intravenous Injection ◽  
Bacterial Endotoxin ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Single Intravenous Injection ◽  
Shwartzman Reaction ◽  
Endogenous Serum Pyrogen ◽  
Indirect Action ◽  
Local Shwartzman Reaction ◽  
Bacterial Products

The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

scholarly journals THE TRANSPORT OF SODIUM INTO HUMAN ERYTHROCYTES IN VIVO

1955 ◽  
Vol 38 (3) ◽  
pp. 389-404 ◽  
Author(s):  
G. Lennard Gold ◽  
A. K. Solomon
Keyword(s):  
Young Adults ◽  
Theoretical Analysis ◽  
Intravenous Injection ◽  
Specific Activity ◽  
Red Cells ◽  
Red Cell ◽  
Single Intravenous Injection ◽  
Normal Individuals

The relative Na24 specific activity of red cells and plasma was measured at periods up to 30 hours following a single intravenous injection of Na24 in normal healthy young adults. The average specific activity of the red cells relative to that of the plasma at 24 hours and beyond was found to average 0.83 ± 0.05 in a series of five normal individuals, significantly different from 1.0. This indicates that all the intracellular Na is not exchangeable in 24 hours, and confirms earlier in vitro results. The red cell Na concentration in man was shown to be 12.1 ± 1.1 m.eq. Na/liter red cell, as measured in a series of nineteen normal healthy young adults. A theoretical analysis of the data on exchangeable cell Na suggests that the red cell Na (5.3 m.eq. Na/liter blood) is divided into a fast compartment comprising 4.25 m.eq. Na/liter blood, and a slow compartment comprising 1.07 m.eq. Na/liter blood. If these compartments are arranged in parallel, the flux between plasma and fast compartment is 1.32 m.eq. Na/liter blood hour, and that between plasma and slow compartment is 0.016 m.eq. Na/liter blood hour. Results of experiments on two patients with congenital hemolytic jaundice suggest that the fraction of slowly exchanging Na may increase with the age of the red cell.

scholarly journals STUDIES OF THE EFFECT OF BACTERIAL ENDOTOXINS ON RABBIT LEUCOCYTES

1953 ◽  
Vol 98 (4) ◽  
pp. 349-364 ◽  
Author(s):  
Leighton E. Cluff
Keyword(s):  
Buffy Coat ◽  
Development Of Resistance ◽  
Bacterial Endotoxins ◽  
Leucocyte Migration ◽  
Shwartzman Reaction ◽  
Rapid Removal ◽  
And Migration ◽  
Shwartzman Phenomenon ◽  
Reticulo Endothelial System ◽  
Development Of Tolerance

Bacterial endotoxin injected intravenously into rabbits inhibited the migration of leucocytes from the buffy coat of centrifuged blood (4). Repeated daily injections of endotoxin resulted in the rabbits becoming resistant to the fever-inducing action of the toxin, and migration of leucocytes from centrifuged blood was no longer inhibited by injection of the toxin. Leucocyte migration from the buffy coat of centrifuged blood after injection of toxin into the rabbits appeared gradually over the first few days of repeated injections, and disappeared during the 10 to 15 days after cessation of daily injections of toxin. The resistance to endotoxin, demonstrated by leucocyte migration and pyrogen tolerance, could not be passively transferred with serum from resistant animals, and was non-specific, in that resistance to one endotoxin conferred some resistance to toxin from an organism of a different species. No relationship could be demonstrated between precipitin titer and resistance. Thorotrast abolished resistance to the fever-inducing activity of endotoxin, but its effect on leucocyte resistance was not clear, since when injected alone it inhibited migration of leucocytes from the buffy coat of centrifuged blood. The suggestion is made that the failure of toxin to inhibit the migration of leucocytes from resistant rabbits is due either to the presence of leucocytes which have become adapted to the toxin by repeated exposure, or to rapid removal of the toxin by the reticulo-endothelial system. It is unlikely that leucocyte resistance participates in the development of tolerance to the fever-inducing action of endotoxin. However, in view of the participation of the leucocyte in the pathogenesis of the Shwartzman reaction, the presence of leucocytes resistant to endotoxin may be responsible in part for the development of resistance to the Shwartzman phenomenon.

scholarly journals In Vivo Localization of Heterologous Anti-Erythrocyte Antibodies in the Rat Bone Marrow and Their Effect on the Proliferative Capacity of Immature Erythroid Cells

Blood ◽  
1965 ◽  
Vol 25 (2) ◽  
pp. 161-168 ◽  
Author(s):  
TAKEO KUROYANAGI ◽  
MASANOBU SAITO ◽  
AKIRA KURISU
Keyword(s):  
Bone Marrow ◽  
Intravenous Injection ◽  
Tritiated Thymidine ◽  
Inhibitory Effect ◽  
Red Cell ◽  
Proliferative Capacity ◽  
Rat Bone ◽  
Incomplete Antibody

Abstract The in vivo localization of heterologous anti-erythrocyte antibodies in the rat bone marrow was determined by the I131-labeled antibody technic. I131-labeled anti-erythrocyte antibodies localized specifically in the bone marrow indicating the presence of localizing antibody. Both the localizing antibody and the incomplete antibody were thermostable, whereas hemolysins and hemagglutinins were thermolabile. Following an intravenous injection of antierythrocyte antibodies in rats, hemolysins and hemagglutinins were cleared rapidly from the plasma. The incomplete antibodies became attached to circulating red cells within 6 hours and red cell sensitization persisted for 1 week. The localizing antibody localized in the bone marrow within 30 minutes, leaving no activity in plasma. The anti-erythrocyte antibodies markedly reduced the uptake of tritiated thymidine by erythroblasts in vitro, demonstrating their inhibitory effect on the proliferative capacity of erythroblasts.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoporosis Treatment ◽  
Inhibitory Effect ◽  
Specific Gene ◽  
Actin Ring ◽  
Treatment Target ◽  
Significant Inhibitory Effect ◽  
Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

Sign in / Sign up

Export Citation Format

Share Document