The inhibition of angiogenesis in vivo as a result of the inhibition of Ets-1 transcription factor expression by the ets-1 phosphorothioate antisense oligodeoxynucleotide 5'-AGATCGACGGCCGCCTTCAT-3' has been proven by experiments with chicken embryos. Thus, participation of the Ets-1 transcription factor in the formation of new blood vessels in vivo has been demonstrated. Furthermore, it is shown that the angiostatic effect of the fungal metabolite and angiogenesis inhibitor fumagillin is mainly a result of its ability to inhibit Ets-1 expression.
A plate dialyser requiring an extracorporeal blood volume of 1.5 ml was developed to dialyse conscious rats. In experiments in vitro and in vivo its function was tested. The in vitro clearances of urea, creatinine and potassium were 126+/-9 ml/min/m2, 70.5+/-9 ml/min/m2, and 132.5+/-13 ml/min/m2, respectively. The method appears to be suitable for pharmacological and toxicological studies.
In vitro 14C-Methyl-Phalloidin is found to be well dialysable; in vivo dialysis is less effective. In rats the application of 2 mg/kg Phalloidin i.v. led to death after 106 minutes on the average. Hemodialysis with electrolyte-glucose solution or with plasma protein solution immediately started after Phalloidin injection did not alter the survival time significantly. Only a group of rats which was cross dialysed immediately after intoxication showed a statistically insignificant prolongation of survival time of 16 minutes. The histomorphological findings of the liver were similar in all groups. We found a phalloidinic vacuolisation of the cytoplasm of the lobular periphery, hemorrhagic necrosis and also fatty changes in the periphery of the lobule with small fat droplets and pycnosis of nuclei. Specific Phalloidin effects, too, were found in the liver of both animals used in cross-dialysis, which proves that Phalloidin is dialysable by this method.
The bovine protease inhibitor aprotinin (Trasylol) has a high affinity to the kidney and is preferentially pinocytized in the proximal tubule. After i.v. injection of 1mug 124 I aprotinin the blood content decreases to 2.8% of the primary injected amount within 3 hrs, while simultaneously each kidney contains 29%. This substance was used to test whether or not a peptide which is pinocytized, is released in the intact form into the peritubular blood. By a cross circulation technique with two unilaterally nephrectomized rats we were unable to detect any transport of pinocytized, intact peptide through the proximal tubule cell over the observed cross circulation period of 1-8 hrs even when using 5000 times the above dosage. Since the total amount of aprotinin in the kidney is immunologically reactive (ca. 97%), and 65% of the radioactivity in the blood is not reactive after 6 hrs, we believe that the last step in the absorption process consists in digestion inside the lysosomes and instantaneous release of the split products into the blood.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.