Evaluation of a New Preparation of Urokinase

1973 ◽  
Vol 30 (01) ◽  
pp. 114-122
Author(s):  
C.R.M Prentice ◽  
K.M Rogers ◽  
G.P McNicol
Keyword(s):  
Body Weight ◽  
Maintenance Therapy ◽  
Initial Dose ◽  
Fibrinolytic Activity ◽  
Pharmacological Effect ◽  
Whole Body ◽  
Fibrinolytic Agent ◽  
Thromboplastic Activity

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.

scholarly journals In Vivo Radioprotective Activity of Cell-Permeable Bifunctional Antioxidant Enzyme GST-TAT-SOD against Whole-Body Ionizing Irradiation in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jianru Pan ◽  
Huocong He ◽  
Ying Su ◽  
Guangjin Zheng ◽  
Junxin Wu ◽  
...  
Keyword(s):  
Growth Rate ◽  
Antioxidant Activity ◽  
Body Weight ◽  
Whole Body ◽  
White Pulp ◽  
Radioprotective Activity ◽  
Significant Difference ◽  
Wbc Count

GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST-TAT-SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST-TAT-SOD-pretreated group. Furthermore, GST-TAT-SOD pretreatment increased resistance against 8 Gy whole-body irradiation and enhanced 30 d survival. The overall effect of GST-TAT-SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST-TAT-SOD would be a safe and potentially promising radioprotector.

scholarly journals Safety Assessement And Pharmacological Effect of Algal Oil Omega 3-6 Capsule Rich In Dha, Dpa, Epa From Oil of Heterotrophic Marine Microalga Schizochytrium mangrovei TB17 on the Experimental Animals

2018 ◽  
Vol 40 (2) ◽  
pp. 193-202
Author(s):  
Le Thi Thom ◽  
Nguyen Hoang Ngan ◽  
Dang Diem Hong
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Human Health ◽  
Pharmacological Effect ◽  
Learning Ability ◽  
Whole Body ◽  
Omega 3 ◽  
Experimental Animals ◽  
Marine Microalga ◽  
Algal Oil

Recently, heterotrophic marine microalga Schizochytrium mangrovei has been shown to be rich in omega 3-6 fatty acids, mainly docosahexaenoic acid (DHA), ecosapentanoic acid (EPA) and docosapentanoic acid (DPA). These fatty acids play an important role on human health. In this article, we presented results of safety assessment and pharmacological effect of Algal Oil Omega 3-6 (AOO-3-6) which made from oil of S. mangrovei TB17 on the experimental animals after 90 days of use. The results of acute toxicity study showed that by oral administration of the AOO-3-6 on white mice at the highest dose of 15.27 g total of DHA, EPA, DPA / kg of whole body of mice/ day (the dosage was 113.63 times higher than the mice dose), the LD50 was not determined. It means that AOO-3-6 capsules was no signs toxicity. At doses of 78.4 mg and 352.8 mg of total of DHA, EPA, DPA/ kg of whole bode of rat/ day (effec-tive dose znd 4.5 times higher than the expected dose) for 90 continuous days on the mice didn’t affect the normal increment of body weight, hematological indices, biochemical indicators; function of liver and kid-ney; histopathology of liver, kidney, spleen of white rats. At the same time, at doses of 134.4 and 403.2 mg total of DHA, EPA and DPA/kg of body weight/day improved the ability to learn, remember on the mice. In addition, it also allowed building its reflexes sustainability in finding food to be faster with shorter reflectance time. As a result, AOO-3-6 capsules are safe and have the ability to improve memory, learning ability on the mouse which can be used for functional food for human health.

Effect of l-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo

1992 ◽  
Vol 83 (2) ◽  
pp. 183-190 ◽  
Author(s):  
P. C. Dagnelie ◽  
D. K. Menon ◽  
I. J. Cox ◽  
J. D. Bell ◽  
J. Sargentoni ◽  
...  
Keyword(s):  
Body Weight ◽  
Human Liver ◽  
Pulse Sequence ◽  
Whole Body ◽  
Maximal Increase ◽  
Normal Human Liver ◽  
Normal Human ◽  
Biochemical Pathology

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of l-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34–44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of l-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the β-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean ± sem: 98 ± 12%, P<0.005) and [Pi]/[ATP] (−33 ± 3%, P<0.001) were observed approximately 45 min after the l-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 ± 6% (P<0.05), which was independent of the l-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of l-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after l-alanine infusion. No significant increases in other metabolites contributing to the phosphomonoester or phosphodiester resonances in vivo were observed, suggesting that the rise in [phosphomonoesters] observed in vivo was caused by increasing concentrations of 3-phosphoglycerate, and that phosphoenolpyruvate contributed to the rise in [phosphodiesters]. 5. These results show that l-alanine infusion leads to consistent changes in the 31P n.m.r. spectra of the human liver owing to increased concentrations of gluconeogenic intermediates. The ‘n.m.r.-alanine test’ may constitute a useful tool for studies of gluconeogenesis and hepatic biochemical pathology in vivo.

scholarly journals Methodological approaches to assess body-weight regulation and aetiology of obesity

2000 ◽  
Vol 59 (3) ◽  
pp. 405-411 ◽  
Author(s):  
Amelia Marti ◽  
Carlos De Miguel ◽  
Susan A Jebb ◽  
Max Lafontan ◽  
Martine Laville ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Laboratory Animals ◽  
Positive Energy ◽  
Weight Regulation ◽  
Body Weight Regulation

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention.

Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies

2002 ◽  
Vol 41 (03) ◽  
pp. 129-134 ◽  
Author(s):  
A. Wolski ◽  
E. Palombo-Kinne ◽  
F. Wolf ◽  
F. Emmrich ◽  
W. Becker ◽  
...  
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Synovial Membrane ◽  
In Vitro Release ◽  
Peritoneal Macrophages ◽  
Lymphoid Organs ◽  
Whole Body ◽  
Free Form ◽  
Ankle Joints

Summary Aim: The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/ experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA). Methods: AA rat peritoneal macrophages or lymph node T-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA. Results: In vitro release of 99mTc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joint scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints. Conclusion: While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99mTc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible.

A Simple and Inexpensive Clinical Whole Body Counter

1976 ◽  
Vol 15 (05) ◽  
pp. 248-253
Author(s):  
A. K. Basu ◽  
S. K. Guha ◽  
B. N. Tandon ◽  
M. M. Gupta ◽  
M. ML. Rehani
Keyword(s):  
The Body ◽  
Whole Body ◽  
Vitro Assay ◽  
Body Counter ◽  
Optimum Parameters ◽  
Whole Body Counter ◽  
Single Detector ◽  
Background Index ◽  
Iodide Crystal

SummaryThe conventional radioisotope scanner has been used as a whole body counter. The background index of the system is 10.9 counts per minute per ml of sodium iodide crystal. The sensitivity and derived sensitivity parameters have been evaluated and found to be suitable for clinical studies. The optimum parameters for a single detector at two positions above the lying subject have been obtained. It has been found that for the case of 131I measurement it is possible to assay a source located at any point in the body with coefficient of variation less than 5%. To add to the versatility, a fixed geometry for in-vitro counting of large samples has been obtained. The retention values obtained by the whole body counter have been found to correlate with those obtained by in-vitro assay of urine and stool after intravenous administration of 51Cr-albumin.

Binding of Tissue Plasminogen Activator to Vascular Grafts

1989 ◽  
Vol 61 (01) ◽  
pp. 131-136 ◽  
Author(s):  
Richard A Harvey ◽  
Hugh C Kim ◽  
Jonathan Pincus ◽  
Stanley Z Trooskin ◽  
Josiah N Wilcox ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Polymer Surface ◽  
Enzymic Activity ◽  
Vascular Prostheses ◽  
Chemically Modified ◽  
Insoluble Surfactant ◽  
Tissue Plasminogen

SummaryTissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDM AC). Surfactant- treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I- tPA (5-30 μg 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t½ of appoximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.

Gastric Fibrinolysis

1975 ◽  
Vol 34 (02) ◽  
pp. 409-418 ◽  
Author(s):  
I. M Nilsson ◽  
S.-E Bergentz ◽  
U Hedner ◽  
K Kullenberg
Keyword(s):  
Gastric Ulcer ◽  
Gastric Juice ◽  
High Activity ◽  
Fibrinolytic Activity ◽  
Duodenal Juice ◽  
Bleeding Tendency ◽  
Local Fibrinolysis ◽  
Heated Plates

SummaryGastric juice from 15 normals, 20 patients with gastric ulcer and 4 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhagic gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurrence of plasmin could be demonstrated directly immunologically in the gastric juice. By comparison of plasmin and trypsin in various assays it could further be proved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and α2M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard
Keyword(s):  
Body Weight ◽  
Factor Viii ◽  
Factor Ix ◽  
Clotting Factor ◽  
Blood Ph ◽  
Order Of Magnitude ◽  
Dose Dependent ◽  
Generation Test ◽  
Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

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