Intravenous Administration of Dehydroxymethylepoxyquinomicin With Polymer Enhances the Inhibition of Pancreatic Carcinoma Growth in Mice

SummaryAcute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.

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Prevalence and Induction of Circulating Antibodies against Recombinant Staphylokinase

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642396 ◽

1994 ◽

Vol 71 (01) ◽

pp. 129-133 ◽

Cited By ~ 33

Author(s):

P J Declerck ◽

S Vanderschueren ◽

J Billiet ◽

H Moreau ◽

D Collen

Keyword(s):

Intravenous Administration ◽

Human Subjects ◽

Microtiter Plates ◽

Staphylococcus Aureus Bacteremia ◽

Alternative Agent ◽

Antibody Titers ◽

Potential Alternative ◽

Circulating Antibodies ◽

Low Levels ◽

Antibody Levels

SummaryStreptokinase (SK) is a routinely used thrombolytic agent but it is immunogenic and allergenic; staphylokinase (STA) is a potential alternative agent which is under early clinical evaluation. The comparative prevalence of antibodies against recombinant STA (STAR) and against SK was studied in healthy subjects and their induction with intravenous administration in small groups of patients.Enzyme-linked immunosorbent assays, using microtiter plates coated with STAR or SK and calibration with affinospecific human antibodies, revealed 2.1 to 65 μg/ml (median 11 μg/ml) anti-STAR antibodies and 0.9 to 370 μg/ml (median 18 μg/ml) anti-SK antibodies (p <0.001 vs anti-STAR antibodies) in plasma from 100 blood donors, with corresponding values of 0.6 to 100 μg/ml (median 7.1 μg/ml) and 0.4 to 120 μg/ml (median 7.3 μg/ml), respectively, in 104 patients with angina pectoris. Three out of 17 patients with Staphylococcus aureus bacteremia had significantly increased anti-STAR antibody levels (150, 75 and 75 μg/ml), and STAR neutralizing activities (2.2, 3.6 and 4.1 μg STAR neutralized per ml plasma, respectively). In 6 patients with acute myocardial infarction, given 10 mg STAR intravenously over 30 min, median anti-STAR antibody levels were 3.5 μg/ml at baseline, 2.9 μg/ml at 6 to 8 days and 1.2 μg/ml at 2 to 9 weeks, with median corresponding titers of STAR neutralizing activity at 2 to 9 weeks of 42 μg/ml plasma. Conversely, in 5 patients treated with 1,500,000 units SK over 60 min, median anti-SK antibodies increased from 2.9 μg/ml at baseline to 360 μg/ml at 5 to 10 days, with corresponding median SK neutralizing activities of 13 μg/ml. Antibodies against STAR did not cross-react with SK and vice versa.Plasma from human subjects contains low levels of circulating antibodies against recombinant staphylokinase, and intravenous administration of this compound boosts antibody titers. These antibodies do however not cross-react with streptokinase, whereby the use of these two immunogenic thrombolytic agents would not be mutually exclusive.

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Vampire Bat Salivary Plasminogen Activator Evokes Minimal Bleeding Relative to Tissue-Type Plasminogen Activator as Assessed by a Rabbit Cuticle Bleeding Time Model

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653800 ◽

1995 ◽

Vol 73 (03) ◽

pp. 478-483 ◽

Cited By ~ 7

Author(s):

Michael J Mellott ◽

Denise R Ramjit ◽

Inez I Stabilito ◽

Timothy R Hare ◽

Edith T Senderak ◽

...

Keyword(s):

Factor Viii ◽

Plasminogen Activator ◽

Intravenous Administration ◽

Bleeding Time ◽

Bleeding Risk ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Type Plasminogen Activator ◽

Plasma Factor ◽

Vampire Bat

SummaryCuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p<NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.

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Intrathoracic Platelet Accumulation in the Guinea-Pig Induced by Intravenous Administration of Arachidonic Acid - Effect of Cyclooxygenase and Thromboxane Synthetase Inhibitors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661674 ◽

1986 ◽

Vol 56 (03) ◽

pp. 311-317 ◽

Cited By ~ 1

Author(s):

P A Barrett ◽

K D Butler ◽

R A Shand ◽

R B Wallis

Keyword(s):

Arachidonic Acid ◽

Blood Volume ◽

Intravenous Administration ◽

Guinea Pigs ◽

Human Albumin ◽

Thromboxane Synthetase ◽

Acid Effect ◽

Rapid Accumulation ◽

Platelet Accumulation ◽

High Doses

SummaryIntravenous administration of arachidonic acid to guinea-pigs caused a dose-related, rapid accumulation of 51Cr-labelled platelets in the thorax. Inhibitors of cyclooxygenase inhibited the platelet accumulation, induced by arachidonic acid (30 mg/kg), at doses which did not alter the thoracic blood volume (as measured by 131I-labelled human albumin). Thromboxane synthetase inhibitors had different effects on platelet accumulation depending on the dose. CGS 12970 (3 mg/kg) and N(1-carboxyheptyl) imidazole (100 mg/kg) reduced platelet accumulation. High doses of CGS 12970 and CGS 13080 caused an apparent enhancement of platelet accumulation which was associated with pooling of blood in the thorax, as measured by either 131I-labelled human albumin or 51Cr-labelled erythrocytes. This increase in thoracic blood volume was abolished if the guinea-pigs were also pretreated with diclofenac (1 mg/kg) in addition to the thromboxane synthetase inhibitor. Increases in thoracic blood volume were also obtained following infusions of PGI2 but not PGD2 or PGE2.

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The Effects of Modulation of Prostanoid Metabolism on the Thoracic Platelet Accumulation Induced by Intravenous Administration of Collagen in the Guinea-Pig

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661663 ◽

1986 ◽

Vol 56 (03) ◽

pp. 263-267

Author(s):

K D Butler ◽

R A Shand ◽

R B Wallis

Keyword(s):

Platelet Count ◽

Guinea Pig ◽

Intravenous Administration ◽

Cyclooxygenase Inhibitors ◽

Concomitant Increase ◽

Thromboxane Synthetase ◽

Platelet Accumulation ◽

Related Increase

SummaryThe effects of intravenously administered collagen on the circulatory platelet count, TxB2, 6-keto PGF1α and 51Cr-labelled platelet accumulation in the thorax have been evaluated in the guinea-pig. Administration of collagen induced a dose-related peripheral thrombocytopenia and a concomitant increase in 51Cr-labelled platelets in the thorax. There was also a transient dose-related increase in plasma TxB2 but no change in plasma 6-keto PGF1α levels.The thromboxane synthetase inhibitors tested, reduced the platelet accumulation, but only CGS 13080 significantly inhibited TxB2 production. In contrast all the cyclooxygenase inhibitors tested impaired the elevation of plasma TxB2 after collagen, but only diclofenac inhibited the 51Cr-labelled platelet accumulation.The greater effect of thromboxane synthetase inhibitors compared to cyclooxygenase inhibitors on platelet accumulation in this system cannot be completely explained by the changes measured in the circulating prostanoids.

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CHROMATOGRAPHIC STUDIES ON 131I-COMPOUNDS IN FAECES AND BILE

Acta Endocrinologica ◽

10.1530/acta.0.0470343 ◽

1964 ◽

Vol 47 (2) ◽

pp. 343-352

Author(s):

B. Blomstedt ◽

H. Y. Neujahr

Keyword(s):

Intravenous Administration ◽

Glucuronic Acid ◽

Free Triiodothyronine ◽

Considerable Part ◽

Human Faeces ◽

Total Excretion

ABSTRACT The occurrence of 131I-compounds in human faeces was studied after intravenous administration of 131I-thyroxine. The excretion of the radioactivity during 12 days ranged from 7.8 to 32.1 per cent of the dose administered with a mean of 16.0 (± 1.76). The radioactivity in the faeces was derived from free 131I-thyroxine. The total amount of faeces did not seem to influence the total excretion of the dose administered. After administration of 131I-triiodothyronine to rats and humans, triiodothyronine occurred in the bile mainly conjugated with glucuronic acid, but a considerable part of the radioactivity was found in diiodotyrosine. The radioacivity of human faeces after the administration of 131I-triiodothyronine was derived from free triiodothyronine. After injection of 131I-diiodotyrosine only labelled iodide was detected in the bile of rats. In the bile of humans most of the radioactivity was derived from iodide, and a small part of it was found in diiodotyrosine.

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