Consumption of Hageman Factor Activity in the Generalized Shwartzman Reaction Induced by Liquoid

1970 ◽  
Vol 23 (02) ◽  
pp. 386-404 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Partial Thromboplastin Time ◽  
Lethal Dose ◽  
Control Group ◽  
Factor V ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryThe role of Hageman factor in triggering intravascular coagulation has been studied in rabbits injected intravenously with Liquoid. Besides changes of coagulation parameters characteristic of consumption coagulopathy (e.g. decrease in platelet counts, fibrinogen levels, factor V activity), a pronounced drop in Hageman factor activity was observed after injection of Liquoid. Likewise, the partial thromboplastin time became prolonged.The activation of Hageman factor in vivo could be prevented by intravenous infusion of lysozyme. Twenty min after starting the lysozyme infusion, the partial thromboplastin time became prolonged from a mean of 29 sec to 108 sec. Animals infused with lysozyme and injected with a lethal dose of Liquoid did not develop a consumption coagulopathy. In the same manner, none of 10 animals treated with lysozyme developed the generalized Shwartzman reaction, whereas in the control group 19 out of 20 animals showed fibrin thrombi in the glomerular capillaries.From the present study it may be concluded that the intravascular coagulation process after intravenous injection of Liquoid is triggered by Hageman factor activation.

Hageman Factor Activity in Liquoid-Induced Consumption Coagulopathy

1971 ◽  
Vol 26 (01) ◽  
pp. 058-070 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Intravenous Injection ◽  
Coumarin Derivative ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Platelet Counts ◽  
Shwartzman Reaction ◽  
Initial Drop ◽  
Glomerular Capillaries

Summary1. Consumption coagulopathy was induced by intravenous injection of Liquoid (sodium polyanetholsulfonate) into rabbits. Thirteen out of 21 animals injected with Liquoid showed fibrin formation in the renal glomerular capillaries characteristic of the generalized Shwartzman reaction. In these 13 animals, a pronounced drop in Hageman factor activity was observed in addition to a decrease in platelet counts and fibrinogen levels.2. The consumption coagulopathy induced by Liquoid could be prevented by pretreatment of the rabbits with phenprocoumon, a coumarin derivative. None of 21 rabbits pretreated by this anticoagulant and injected with Liquoid showed fibrin in the renal glomerular capillaries. Phenprocoumon pretreatment did not influence the decrease in platelet counts, but it did significantly diminish the drop in fibrinogen levels. Although disseminated intra vascular coagulation and the generalized Shwartzman reaction could be inhibited by phenprocoumon pretreatment, this anticoagulant could not prevent the initial drop in Hageman factor activity after Liquoid injection.3. Phenprocoumon did not influence the activity or synthesis of Hageman factor. As phenprocoumon pretreatment could not prevent the drop in Hageman factor activity after intravenous injection of Liquoid, it might be concluded that the Hageman factor is either consumed, directly inactivated or destroyed in the animals independent of the presence of the prothrombin complex. These findings support earlier studies which have shown that inhibition of Hageman factor activation in vivo can prevent the generalized Shwartzman reaction induced by Liquoid.

scholarly journals Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1496-1502 ◽  
Author(s):  
PM Sandset ◽  
BJ Warn-Cramer ◽  
SL Maki ◽  
SI Rapaport
Keyword(s):  
Factor Viia ◽  
Factor V ◽  
Activity Levels ◽  
Cell Surfaces ◽  
Extrinsic Pathway ◽  
Intravascular Coagulation ◽  
Disease States ◽  
Shwartzman Reaction ◽  
Thrombotic Complications

Abstract We have reported earlier that immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation (DIC) induced by infusing a low concentration of tissue factor (TF). We now describe the effect of immunodepletion of EPI in rabbits administered endotoxin. Cortisone-treated rabbits were administered anti-rabbit EPI immunoglobulin (IgG) or Fab fragments or were administered control nonimmune material before an injection of endotoxin. In four of seven rabbits administered anti-EPI, plasma EPI activity levels were reduced by 70% to 80% of initial levels for 6 to 8 hours. In these rabbits the endotoxin induced extensive DIC, as evidenced by substantial decreases in fibrinogen, factor V, factor VIII, and platelets, and gross hemorrhagic necrosis of the kidneys due to massive deposition of fibrin in the glomerular microcirculation (the generalized Shwartzman reaction). In three rabbits administered anti- EPI, plasma EPI levels were only transiently reduced. In these rabbits and in four rabbits administered nonimmune IgG or Fab, endotoxin induced minimal to moderate intravascular clotting and deposits of fibrin were not found in the glomerular capillaries. Because it is believed that TF expressed on monocytes triggers endotoxin-induced coagulation, these data are taken as evidence that EPI functions as a natural anticoagulant that can regulate factor VIIa/TF activity expressed on cell surfaces in vivo. They support a hypothesis that EPI prevents thrombotic complications that might otherwise result from exposure of blood to cytokine-induced generation of small amounts of TF on cell surfaces in many inflammatory and infectious disease states.

scholarly journals Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1496-1502 ◽  
Author(s):  
PM Sandset ◽  
BJ Warn-Cramer ◽  
SL Maki ◽  
SI Rapaport
Keyword(s):  
Factor Viia ◽  
Factor V ◽  
Activity Levels ◽  
Cell Surfaces ◽  
Extrinsic Pathway ◽  
Intravascular Coagulation ◽  
Disease States ◽  
Shwartzman Reaction ◽  
Thrombotic Complications

We have reported earlier that immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation (DIC) induced by infusing a low concentration of tissue factor (TF). We now describe the effect of immunodepletion of EPI in rabbits administered endotoxin. Cortisone-treated rabbits were administered anti-rabbit EPI immunoglobulin (IgG) or Fab fragments or were administered control nonimmune material before an injection of endotoxin. In four of seven rabbits administered anti-EPI, plasma EPI activity levels were reduced by 70% to 80% of initial levels for 6 to 8 hours. In these rabbits the endotoxin induced extensive DIC, as evidenced by substantial decreases in fibrinogen, factor V, factor VIII, and platelets, and gross hemorrhagic necrosis of the kidneys due to massive deposition of fibrin in the glomerular microcirculation (the generalized Shwartzman reaction). In three rabbits administered anti- EPI, plasma EPI levels were only transiently reduced. In these rabbits and in four rabbits administered nonimmune IgG or Fab, endotoxin induced minimal to moderate intravascular clotting and deposits of fibrin were not found in the glomerular capillaries. Because it is believed that TF expressed on monocytes triggers endotoxin-induced coagulation, these data are taken as evidence that EPI functions as a natural anticoagulant that can regulate factor VIIa/TF activity expressed on cell surfaces in vivo. They support a hypothesis that EPI prevents thrombotic complications that might otherwise result from exposure of blood to cytokine-induced generation of small amounts of TF on cell surfaces in many inflammatory and infectious disease states.

A Non-Stasis Rabbit Model for the Detection of Factor IX Concentrate Thrombogenicity.

1979 ◽  
Author(s):  
C.V. Prowse ◽  
A.R. Williams
Keyword(s):  
Platelet Count ◽  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Rabbit Model ◽  
Factor Ix ◽  
In Vitro Activity ◽  
Blood Samples ◽  
Intravascular Coagulation

A method has been developed whereby aerial blood samples can be obtained from a rabbit over a period of four hours following infusion of potentially thrombogenic solutions. Infusion of 50 uAg thrombin over JO minutes produced intravascular coagulation for up to three hours after infusion as demonstrated by a decrease in factor VIII, increase in partial thromboplastin time and fibrin(ogen) degradation producta and a positive ethanol gelation teat. No change in fibrinogen, factor DC or platelet count was found. Saline infusion produced no change in any of these parameters.Infusion of a variety of factor IX concentrates at 100 u/kg shewed that those concentrates active in in vitro thrombogenicity teste produced a similar effect to thrombin in vivo and in addition may result in a drop in platelet count. Infesion of concentrates with low in vitro activity did not induce intravascular coagulation.

In vivo protection studies of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice

2017 ◽  
Vol 36 (12) ◽  
pp. 1270-1285 ◽  
Author(s):  
P Kumar ◽  
D Swami ◽  
DP Nagar ◽  
KP Singh ◽  
J Acharya ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Ache Activity ◽  
Lethal Dose ◽  
Acute Poisoning ◽  
Control Group ◽  
Swiss Albino Mice ◽  
Albino Mice ◽  
Brain Ache Activity ◽  
Protection Index

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

Changes in Blood Proaccelerin (Factor V) in Rats with Intestinal Strangulation Obstruction

1964 ◽  
Vol 12 (01) ◽  
pp. 049-063
Author(s):  
A Hauge ◽  
E Amundsen ◽  
B. A Waaler
Keyword(s):  
Small Intestine ◽  
Peritoneal Fluid ◽  
Fibrinogen Level ◽  
Control Group ◽  
Factor V ◽  
Intestinal Strangulation ◽  
Temporary Rise

Summary1. In a group of rats with experimentally arranged strangulation obstruction of the small intestine there ocurred a marked temporary rise in blood fibrinogen during the first 2–4 days after the operation. A marked increase in circulating thrombocytes was also seen in these animals. In a control group of sham-operated animals the blood fibrinogen level and the number of circulating thrombocytes increased much less.2. The proaccelerin-accelerin value in the blood of the animals with strangulation obstruction increased markedly during the first 2–4 days after the operation. The increase was greater than that observed in the group of sham-operated animals.3. In the animals with strangulation obstruction, but not in the sham-operated animals, there occurred a fall in the accelerin capacity of the blood. This fall coincided with the rise in the proaccelerin-accelerin value of the blood, as measured directly.4. It is concluded that some transformation of proaccelerin to accelerin or an accelerin-like intermediate is occurring in vivo in the rats with strangulation obstruction. The peritoneal fluid produced by the strangulated segment of intestine can cause transformation of proaccelerin to accelerin in vitro. This fluid, which is reabsorbed from the peritoneum, may be responsible for the observed transformation in vivo as well.5. The accelerin produced by strangulation fluid may not be identical with the accelerin produced by thrombin.

scholarly journals THE PREVENTION OF THE GENERALIZED SHWARTZMAN REACTION WITH SODIUM WARFARIN

1958 ◽  
Vol 107 (3) ◽  
pp. 377-381 ◽  
Author(s):  
Sandor S. Shapiro ◽  
Donald G. McKay
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Control Group ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravascular Coagulation ◽  
Intravenous Injections ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Kidney Liver ◽  
Intravenous Sodium

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis. It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.

scholarly journals In vivo antiplasmodial potential of aqueous seed extract of Ricinus communis

2019 ◽  
Vol 8 (2) ◽  
pp. 133-138
Author(s):  
Peace ME. Ubulom ◽  
Ette O. Ettebong ◽  
Edidiong J. Udofia ◽  
Rachel S Inyang Etuk
Keyword(s):  
Acute Toxicity ◽  
Ricinus Communis ◽  
Lethal Dose ◽  
Suppressive Effect ◽  
Seed Extract ◽  
Toxicity Study ◽  
Control Group ◽  
Active Principle ◽  
Acute Toxicity Study

Introduction: Ricinus communis is used by the people of Niger-Delta region of Nigeria, for the treatment of various ailments, especially malaria. This study evaluated the antiplasmodial potentials of the aqueous seed extract of R. communis, using Plasmodium berghei berghei. Methods: Acute toxicity study was carried out to determine the median lethal dose (LD50) of the extract. Antiplasmodial effect of the extract was assessed in suppressive, repository/ prophylactic and curative models, using Swiss albino mice (15-29 g). Mice were infected intraperitoneally with 0.2 mL of parasitized blood. Extract doses administered were 54.77, 109.54 and 164.32 mg/kg/d of the seed extract and each dose had 6 replicates. Artesunate (5 mg/kg/d) and pyrimethamine (1.2 mg/kg/d) were used as standard drugs, while distilled water (10 mL/kg/d) served as control. Results: Acute toxicity study produced LD50 of 547.72 mg/kg. The extract demonstrated a dosedependent reduction in parasitaemia in all tests. At the end of 4-day test, suppressive effect of 20.80, 49.00, 75.00 and 88.40% were obtained for doses 54.77, 109.54 and 164.32 mg/kg/d of the seed extract and artesunate, respectively. In the repository test pyrimethamine was more potent (72.26%) than the seed extract (9.47%–51.42%). The extract also exhibited appreciable curative effect. The activity of the seed extract was significant when compared with the control (P < 0.05). Mice treated with the seed extract and drugs survived for longer duration than the control group. Conclusion: The aqueous seed extract of R. communis has antiplasmodial potential and its active principle should be elucidated and further investigated to help in the ongoing fight against malaria.

Evaluation of salinomycin isolated from Streptomyces albus JSY-2 against the ciliate, Ichthyophthirius multifiliis

Parasitology ◽  
2018 ◽  
Vol 146 (4) ◽  
pp. 521-526 ◽  
Author(s):  
Jia-Yun Yao ◽  
Ming-Yue Gao ◽  
Yong-Yi Jia ◽  
Yan-Xia Wu ◽  
Wen-Lin Yin ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Effective Concentration ◽  
Control Group ◽  
Ichthyophthirius Multifiliis ◽  
Antiparasitic Activity ◽  
H Nmr ◽  
Streptomyces Albus ◽  
C Nmr

AbstractThe present study was undertaken to investigate the antiparasitic activity of extracellular products of Streptomyces albus. Bioactivity-guided isolation of chloroform extracts affording a compound showing potent activity. The structure of the compound was elucidated as salinomycin (SAL) by EI-MS, 1H NMR and 13C NMR. In vitro test showed that SAL has potent anti-parasitic efficacy against theronts of Ichthyophthirius multifiliis with 10 min, 1, 2, 3 and 4 h (effective concentration) EC50 (95% confidence intervals) of 2.12 (2.22–2.02), 1.93 (1.98–1.88), 1.42 (1.47–1.37), 1.35 (1.41–1.31) and 1.11 (1.21–1.01) mg L−1. In vitro antiparasitic assays revealed that SAL could be 100% effective against I. multifiliis encysted tomonts at a concentration of 8.0 mg L−1. In vivo test demonstrated that the number of I. multifiliis trophonts on Erythroculter ilishaeformis treated with SAL was markedly lower than that of control group at 10 days after exposed to theronts (P < 0.05). In the control group, 80% mortality was observed owing to heavy I. multifiliis infection at 10 days. On the other hand, only 30.0% mortality was recorded in the group treated with 8.0 mg L−1 SAL. The median lethal dose (LD50) of SAL for E. ilishaeformis was 32.9 mg L−1.

scholarly journals Antiplasmodial activity of methanol leaf extract of Citrus aurantifolia (Christm) Swingle

2019 ◽  
Vol 8 (4) ◽  
pp. 274-280
Author(s):  
Ette Ettebong ◽  
Peace Ubulom ◽  
Aniekeme Etuk
Keyword(s):  
Leaf Extract ◽  
Lethal Dose ◽  
Intraperitoneal Administration ◽  
Antiplasmodial Activity ◽  
Control Group ◽  
Standard Drug ◽  
Citrus Aurantifolia ◽  
Low Toxicity ◽  
Different Doses

Introduction: Citrus aurantifolia (Christm) is a plant used for the treatment of various ailments including malaria. This study aimed to evaluate the in vivo antiplasmodial efficacy of methanol leaf extract of C. aurantifolia in Swiss albino mice. Methods: The median lethal dose (LD50) was determined by intraperitoneal administration of different doses of the extract (100–4000 mg/kg) to 6 groups of 3 mice each and the animals were observed for 24 hours for physical signs of toxicity. To evaluate the antiplasmodial activity of the extract, three models were used: suppressive, curative and repository. Doses of the extract used were 320, 640 and 960 mg/kg/d in mice, with Chloroquine (5 mg/kg/d) as standard drug. Pyrimethamine (1.2 mg/kg/d) was used as the standard drug for the repository test and distilled water (10 mL/kg/d) as control in all models. Results: In all models, the low dose (320 mg/kg) of the extract produced the highest chemosuppressive effects in all models (P < 0.001). Mice treated with extract lived longer than those in the control group (P < 0.001). Phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, tannins and cardiac glycosides and the LD50 of 3280 mg/kg ± 0.01 shows that the extract has low toxicity. Conclusion: The result of this study shows that C. aurantifolia has antiplasmodial properties which support its use in ethnomedicine in the treatment of malaria.

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