Enhancement of Fibrinolytic and Thrombolytic Potential in the Rat by Treatment with an Anabolic Steroid, Furazabol

1976 ◽  
Vol 36 (02) ◽  
pp. 451-464 ◽  
Author(s):  
Toshihiko Kumada ◽  
Yasushi Abiko
Keyword(s):  
Plasminogen Activator ◽  
Lung Tissue ◽  
Anabolic Steroid ◽  
Plasma Cholesterol ◽  
Venous Occlusion ◽  
Pulmonary Tissue ◽  
Daily Dose ◽  
Plasma Recalcification Time ◽  
Recalcification Time

SummaryThe effect of long-term ingestion of an anabolic steroid, furazaboi, was studied on coagulo-fibrinolytic systems in the rat.During the administration of furazabol at the daily dose of 0.04, 0.2 or 1 mg/rat for 3 months, the most remarkable changes were increase in the plasminogen activator activity in blood and the lung tissue and decrease in plasma fibrinogen level as well as decrease in plasma cholesterol. It was a very important finding that in most of the rats the furazabol treatment was effective in reducing susceptibility to lactic acidosis-induced pulmonary thrombosis. No meaningful changes were observed in other parameters tested including ADP-induced platelet aggregability, plasma recalcification time, plasma plasminogen, plasma antiplasmin activity, plasminogen activator content of tissues other than the lungs and the release of vascular activator induced by venous occlusion. One month after cessation of the furazabol treatment, these altered parameters tended to return to normal.Independently on the furazabol treatment, highly significant positive correlation existed between the plasma activator activity and the pulmonary tissue activator content. This indicated that the major source of plasma activator in the rat was the lung tissue and that the furazabol treatment increased the circulating activator activity through enhancing activator content in the lungs.

Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System

1988 ◽  
Vol 59 (02) ◽  
pp. 299-303 ◽  
Author(s):  
Grazia Nicoloso ◽  
Jacques Hauert ◽  
Egbert K O Kruithof ◽  
Guy Van Melle ◽  
Fedor Bachmann
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Activator Inhibitor ◽  
Pai 1

SummaryWe analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.

Plasma Fibrinolytic Activity Following Oral Anabolic Steroid Therapy

1975 ◽  
Vol 34 (01) ◽  
pp. 236-245 ◽  
Author(s):  
I. D Walker ◽  
J. F Davidson ◽  
P Young ◽  
J. A Conkie
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Anabolic Steroid ◽  
Fibrinolytic Activity ◽  
Anabolic Steroids ◽  
Long Term Effects ◽  
Lysis Time ◽  
Detailed Evaluation ◽  
Euglobulin Lysis Time

SummarySix anabolic steroids were assessed for their ability to enhance plasma fibrinolytic activity in males with ischaemic heart disease. Five 17α-alkylated steroids (Ethyloestrenol, Norethandrolone, Methandienone, Methylandrostenediol and Oxymetholone) were examined and all produced a significant increase in plasma plasminogen activator as measured by the euglobulin lysis time. The only non-17α-alkylated steroid studied (Methenolone acetate) failed to enhance fibrinolysis. The 17α-alkylated steroids studied all deserve more detailed evaluation of their long term effects on plasma fibrinolytic activity.

Behaviour and Quantitation of Extrinsic (Tissue-Type) Plasminogen Activator in Human Blood

1983 ◽  
Vol 50 (02) ◽  
pp. 518-523 ◽  
Author(s):  
C Kluft ◽  
A F H Jie ◽  
R A Allen
Keyword(s):  
Plasminogen Activator ◽  
Venous Occlusion ◽  
Tissue Type ◽  
Functional Assay ◽  
Uterine Tissue ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Baseline Values

SummaryFunctional assay of extrinsic (tissue-type) plasminogen activator (EPA) in plasma on fibrin plates was evaluated. Using specific quenching antibodies, we demonstrated the method to be specific for EPA under all conditions tested. Contributions of urokinases and intrinsic activators were excluded. The quantity of EPA in blood samples, as compared with purified uterine tissue activator, shows 1 blood activator unit (BAU) to be comparable to 0.93 ng.The median values for EPA activity for healthy volunteers were: baseline, 1.9 BAU/ml (n = 123); diurnal, 5.5 BAU/ml (n = 12); DDAVP administration, 11.7 BAU/ml (n = 39); exhaustive exercise, 25 BAU/ml (n = 24); venous occlusion (15 min), 35 BAU/ml (n = 61). A large inter-individual variation in EPA activity was found, while individual baseline values tended to be constant for periods of weeks.In vitro in blood EPA activity shows a disappearance of 50% in about 90 min at 37° C; EPA activity in euglobulin fractions is stable for ≤2 hr at 37° C.A rapid decrease in EPA activity occurs in vivo, as noted after extracorporal circulation and exercise stimulation (t½ decay, 2-5 min).

scholarly journals Control of Graves’ hyperthyroidism with very long-term methimazole treatment: a clinical trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fereidoun Azizi ◽  
Hengameh Abdi ◽  
Atieh Amouzegar
Keyword(s):  
Low Dose ◽  
Reference Range ◽  
Antithyroid Drug ◽  
Therapeutic Modality ◽  
Thyroid Status ◽  
Antithyroid Drug Therapy ◽  
Daily Dose ◽  
Prevention Of Relapse

Abstract Background Long-term antithyroid drug therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years. Methods Fifty nine patients with Graves’ disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years. Results Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study. Conclusions Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research. Trial registration IRCT201009224794N1, 2010-10-25. Retrospectively registered. https://www.irct.ir/trial/5143.

PHYSICAL ACTIVITY RELEASES TISSUE PLASMINOGEN ACTIVATOR FROM EXERCISING PARTS OF BODY

1987 ◽  
Author(s):  
I Keber ◽  
K Potisk ◽  
D Keber ◽  
M Stegnar ◽  
N Vene
Keyword(s):  
Physical Activity ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Venous Occlusion ◽  
Clot Lysis ◽  
Lysis Time ◽  
Tissue Plasminogen ◽  
Euglobulin Clot Lysis Time ◽  
The Difference

To determine the origin of tissue plasminogen activator (t-PA) release during physical activity, we studied the separate and combined effects of venous occlusion and acute physical activity on t-PA release in arm and leg. In 15 healthy volunteers 20 min venous occlusions of arm and leg were performed simultaneously before physical activity ( maximal stress testing on treadmill)(occlusion I), immediately after physical activity and 45 min later (occlusion II). Blood samples were drawn from unoccluded arm before occlusion and after physical activity, and from occluded arm and leg after occlusion. Fibrinolytic activity was measured by euglobulin clot lysis time (ECLT) and t-PA activity assay. The amount of released t-PA during different stimuli (fibrinolytic potential) was calculated as the difference between post- and prestimulation fibrinolytic activity. Before physical activity there was a great increase in fibrinolytic activity due to t-PA in the occluded arm but no increase in the occluded leg. Physical activity itself caused a similar increase of systemic fibrinolytic activity as arm occlusion locally. After physical activity arm occlusion evoked equally good response than before it. Fibrinolytic activity during leg occlusion behaved differently: there was an increase in t-PA activity in the occluded leg which persisted one hour after physical activity, when systemic fibrinolytic activity already fell to initial level.These results demonstrated that walking and running triggered t-PA release from the leg vessels. Since leg occlusion was not a stimulus for t-PA release, it served only as a method to demonstrate the effect of physical activity.

scholarly journals POS0338 STEROID-SPARING EFFECT OF ANAKINRA IN GIANT-CELL ARTERITIS: A CASE SERIES WITH CLINICAL, BIOLOGICAL AND ICONOGRAPHIC LONG-TERM ASSESSMENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 397.1-397
Author(s):  
S. Deshayes ◽  
K. Ly ◽  
V. Rieu ◽  
G. Maigné ◽  
N. M. Silva ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Interleukin 1 ◽  
Oral Prednisone ◽  
Large Vessel ◽  
Daily Dose ◽  
Sparing Effect ◽  
Steroid Sparing

Background:The treatment of giant cell arteritis (GCA) relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-interleukin-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to interleukin-6, interleukin-1 also appears to play a significant role in GCA pathophysiology.Objectives:We report herein the efficacy of anakinra, an interleukin-1 receptor antagonist, in 6 GCA patients exhibiting corticosteroid dependence or resistance, specifically analyzing the outcome of aortitis in 4 of them, and including the long-term follow-up of 2 previously described patients (1).Methods:This retrospective study analyzed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis.Patients had to satisfy the following two criteria to be enrolled in this retrospective study. First, their diagnosis of GCA should be based on the fulfillment of at least 3 criteria of the American College of Rheumatology (ACR) for GCA or on the satisfaction of 2 of these criteria along with the demonstration of LVI on imaging. Second, patients should have received anakinra because of corticosteroid dependence or resistance.Corticosteroid dependence was defined as ≥2 relapses or the combination of 2 of the following criteria: a daily dose of oral prednisone >20 mg/day (or 0.3 mg/kg) at 6 months; a daily dose of oral prednisone >10 mg/day (or 0.2 mg/kg) at 12 months; and/or a treatment maintained >24 months because of a relapsing disease course. Corticosteroid resistance was defined as persistent increased inflammatory parameters at month 3 despite a steroid dosage over 0.5 mg/kg.Results:After a median duration of anakinra therapy of 19 [18–32] months, all 6 patients exhibited complete clinical and biological remission. Among the 4 patients with large-vessel involvement, 2 had a disappearance of aortitis under anakinra, and 2 showed a decrease in vascular uptake. After a median follow-up of 56 [48–63] months, corticosteroids were discontinued in 4 patients, and corticosteroid dosage could be decreased to 5 mg/day in 2 patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 hours. Three patients experienced transient injection-site reactions, and 1 patient had pneumonia.Figure 1.Steroid dosages before and after the introduction of anakinra in 6 patients with giant-cell arteritis and corticosteroid dependence or resistance. The black arrow indicates the time of anakinra introduction.Conclusion:In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.References:[1]Ly K-H, Stirnemann J, Liozon E, Michel M, Fain O, Fauchais A-L. Interleukin-1 blockade in refractory giant cell arteritis. Joint Bone Spine 2014;81:76–8.Disclosure of Interests:Samuel Deshayes: None declared, Kim LY: None declared, Virginie Rieu: None declared, Gwénola Maigné: None declared, Nicolas Martin Silva: None declared, Alain Manrique: None declared, Jacques Monteil: None declared, Hubert de Boysson Speakers bureau: Roche-Chugai, Grant/research support from: Roche-Chugai, Achille Aouba Grant/research support from: SOBI

scholarly journals Long-Term Ethanol Consumption Leadsto Lung Tissue Oxidative Stress and Injury

2010 ◽  
Vol 3 (6) ◽  
pp. 414-420 ◽  
Author(s):  
Subir Kumar Das ◽  
Sukhes Mukherjee
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Matrix Metalloproteinase ◽  
Lung Tissue ◽  
Ethanol Consumption ◽  
Ethanol Exposure ◽  
Lung Homogenate ◽  
Ethanol Administration ◽  
Metalloproteinase Activity

Background: Alcohol abuse is a systemic disorder. The deleterious health effects of alcohol consumption may result in irreversible organ damage. By contrast, there currently is little evidence for the toxicity of chronic alcohol use on lung tissue. Hence, in this study we investigated long-term effects of ethanol in the lung.Results: Though body weight of rats increased significantly with duration of exposure compared to its initial weight, there was no significant change in relative weight (g/100 g body weight) of lung due to ethanol exposure. The levels of thiobarbituric acid reactive substances (TBARS), nitrite, protein carbonyl, oxidized glutathione (GSS G), redox ratio (GSS G/ GSH ) and GST activity elevated; while reduced glutathione (GSH ) level and activities of glutathione reductase (GR), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and Na+K+ATPase reduced significantly with duration of ethanol exposure in the lung homogenate compared to the control group. Total matrix metalloproteinase activity elevated in the lung homogenate with time of ethanol consumption. Histopathologic examination also demonstrated that severity of lung injury enhanced with duration of ethanol exposure.Methods: 16–18 week-old male albino Wistar strain rats weighing 200–220 g were fed with ethanol (1.6 g/kg body weight/day) up to 36 weeks. At the end of the experimental period, blood samples were collected from reteroorbital plexus to determine blood alcohol concentration and the animals were sacrificed. Various oxidative stress-related biochemical parameters, total matrix metalloproteinase activity and histopathologic examinations of the lung tissues were performed.Conclusions: Results of this study indicate that long-term ethanol administration aggravates systemic and local oxidative stress, which may be associated with lung tissue injury.

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