Blood activity

Rocks Soils Fodder Winter Sheep Sheep crops wheat wool blood Activity of sheep glutathion peroxidase ferment... 

Cook NS, Zerwes H-G, Tapparelli C et al. (1993) Platelet aggregation and fibrinogen binding in human, rhesus monkey, guinea-pig, hamster and rat blood activation by ADP and thrombin receptor peptide and inhibition by glycoprotein Ilb/IIIa antagonists. Thromb Haemostasis 70 531-539... 

With optimal treatment the gland decreases in size, but overtreatment leading to low hormone concentrations in the blood activates the pituitary feedback system, inducing TSH secretion and goitre. 

Therapeutic doses of morphine can alter the blood activities of amylase, lipase, lactate dehydrogenase, creatine phosphokinase, and leucine aminopeptidase, BSP retention, and urine glucose concentration (Benedict s) (57-59). 

The methoxytetrahydropyran moiety has been exploited by other groups. Merck Frosst identified a class of lignans derived from a natural product, Justicidin E, as moderately potent redox inhibitors of 5-LO (163). Abbott also described compounds in this arena (164). These compounds were very weak inhibitors of 5-LO in broken cell preparations, as was ZD2138, although many compounds with potent whole blood activity were obtained. These data imply a different mode of action for this series than direct 5-LO inhibition and are inconsistent with a substrate inhibitor. 

Figure 7.17 shows a representative time versus blood activity curve for °Y-DOTATOC in a healthy dog. While there was no significant difference between the pharmacokinetics of the agent in a tumour bearing dog and a healthy dog, a biphasic pattern can be observed with very similar constants for Y-DOTATATE. 

FIG. 7.17. Representative time versus blood activity curve of -DOTATOC in a healthy dog. 

A series of 60-s acquisition images is obtained for the next 64 min (at the 247 keV, higher energy peak of inIn, with a 20% window). Hourly images were obtained for the next 4 h. Blood samples were also obtained at 1, 2, 3, 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 210, and 240 min after administration of the inIn-labeled reagents. The 1-min blood sample served as the 100% blood activity reference standard. 

Despite only a minor difference in the chemical structures of vinblastine and vincristine, the clinical effects differ considerably. Surprisingly there is no clinical evidence of cross resistance between them, or with radiation and other presently known oncolytic agents. The rise and fall of the blood activity level of vincristine is steeper than that of vinblastine.The dosage requirements of both alkaloids differ markedly the weekly intravenous dose of vinblastine for humans is 0.1—0.2 mg per kg, that of vincristine, however, is approximately one tenth of this. Concerning the side-effects, vincristine shows more neurotoxic effects and vinblastine is considered to have more potency in bone-marrow depression. This is not without consequences on human therapy therapy is limited by bone-marrow depression with vinblastine and neuromuscular effects, with vincristine. Early symptoms of side-effects are vomiting, fever, and exanthemes. Late symptoms are C.N.S. disturbances, alopecia, and leukopenia. C.N.S. disturbances are manifested by various symptoms such as paresthesias, neuritis, paresis, and muscular atrophy, accompanied by quenched reflexes. Even behaviour may be affected after a long period of treatment. But why do all these side-effects happen, when Vinca alkaloids are unable to pass the blood-brain barrier The only explanation we have at hand is that they are possibly caused by metabolites or breakdown products of the normal biochemical pathways, which are disturbed by the alkaloids. 

Neat VX, 20 ig kg-1, was applied to the skin of four subjects, while four other subjects received 20 p.g kg-1 mixed 1 1 with octylamine, and four others received neat VX, 35 pg kg-1 (Lubash and Clark, 1960). Seven were symptomatic with insomnia, nightmares, lightheadedness, nausea, epigastric discomfort, vomiting and diarrhea. (The whole blood activity was 14-38% of control in these subjects.) The whole blood erythrocyte activity was above 42% of control activity in the five asymptomatic subjects. Plasma and urinary electrolytes, BSP excretion, SGOT, SGPT and serum amylase were all normal following exposure. 

Tc-l,l-ECD is rapidly metabolized in the liver to the monoacid, and also to the diacid, Tc-l,l-EC. At 5 min postinjection, only a third of the blood activity (2.4% ID) was identified as the neutral, parent complex. The remaining activity was a mixture of polar metabolites. The amount of " Tc-bicisate is decreasing rapidly, 10 min after injection there remains little parent complex in the blood for extraction by the brain. Metabolites were identified in urine by HPLC as 19.5% monoacid and 37.8% diacid ( Tc-EC) and 26.3% monoacid and 48.9% diacid at 2 hr and at 6 hr after administration of Tc-l,l-ECD, respectively (Walovitch et al. 1991). 

Whereas filtration and secretion systems in the kidney serve to eliminate drug from the blood into the urine, tubular reabsorption serves to counteract excretion from the blood. Active reabsorption occurs via the proximal... 

The model describes the formation of the main regulators of fibrin polymerization in the blood - activator of clotting (thrombin), the concentration of which is noted by 6, the inhibitor concentration is indicated by cj). Thrombin catalyzes a reaction to convert the precursor of fibrin - fibrinogen into fibrin monomer, concentration of which is denoted by 0, it in turn pol3rmerizes in case and gives thrombus. 

Three TLR9 agonists that induce distinct immune response profiles based on their structures have been selected for clinical studies. lMO-2055 is a lead clinical candidate for the treatment of cancers. The safety and pharmacodynamic activity of lMO-2055 have been studied in Phase-1 rising-dose trials in healthy and cancer subjects. A dose-dependent transient migration of lymphocytes from peripheral blood, activation of surface markers on immune cells, and elevation of plasma cytokines has been observed, consistent with immune-stimulatoiy activity of IMO-2055. No significant acute phase or proinflammatory activity, including no effects on cortisol, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were observed [41, 115-118]. 

---