Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P00750 (
PLA
)
16,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Several experimental studies have demonstrated that ultrasound (US) can accelerate enzymatic fibrinolysis and this effect is further enhanced in the presence of ultrasound contrast agents (UCA). Although UCA have been shown to be safe when administered to ischemic stroke patients, safety information of these agents in the thrombolysis setting is limited. Therefore, in this study we investigated potential adverse effects of acoustic cavitation generated by UCA on
alteplase
(
t-PA
), the drug used for treatment of ischemic stroke patients. A volume of 0.9 mL of
alteplase
was dispensed into a custom-made polyester sample tube. For treatments in the presence or absence of cavitation either 0.1 mL
Optison
or phosphate buffer saline was combined with
alteplase
. Three independent samples of each treatment group were exposed to ultrasound of 2 MHz frequency at three different peak negative acoustic pressures of 0.5, 1.7, and 3.5 MPa for a duration of 60 min. All treatments were carried out in a cavitation detection system which was used to insonify the samples and record acoustic emissions generated within the sample. After ultrasound exposure, the treated samples and three untreated drug samples were tested for their enzymatic activity using a chromogenic substrate. The insonified samples containing
Optison
demonstrated cavitational activity proportional to acoustic pressure. No significant cavitation activity was observed in the absence of
Optison
. Enzymatic activity of
alteplase
in both insonified groups was comparable to that in the control group. These tests demonstrated that exposure of
alteplase
to 60 min of 2 MHz ultrasound at acoustic pressures ranging from 0.5 MPa to 3.5 MPa, in the presence or absence of
Optison
had no adverse effects on the stability of this therapeutic compound.
...
PMID:Stability of alteplase in presence of cavitation. 1806 40
