Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer.
The CO of individual pigs varied from 1.33 to 6.44 l/min. Three-compartmental modeling showed that CO is a determinant of the central compartment volume (V1, r2 = 0.54), fast peripheral compartment volume (V2, r2 = 0.29), steady state distribution volume (Vss, r2 = 0.29), fast distribution clearance (Cl12, r2 = 0.39), and elimination clearance (Cl10, r2 = 0.51). Recirculatory modeling showed that CO is a determinant of total distribution volume (r2 = 0.48), elimination clearance (r2 = 0.54), and some distribution clearances. The pulmonary distribution volume was independent of CO.
Beta-adrenergic agents enhance secretion of phosphatidylcholine (PC) by adult and fetal type II cells. We have previously shown that terbutaline stimulates secretion of PC by fetal type II cells, but the response wanes after 30 minutes. We studied the effects of salmeterol, a highly selective, long-acting beta2-adrenergic agonist that does not cause receptor desensitization, on PC secretion by adult type II alveolar cells in primary culture. Release of lactate-dehydrogenase was < 4% and did not vary with the concentration of salmeterol. Salmeterol stimulated PC secretion in a concentration-dependent manner. The maximum effective-concentration tested was 50 nM and the EC50 was 11.40 +/- 1.14 nM. Propranolol inhibited the effect of salmeterol on release of PC, confirming that the effects of salmeterol are mediated by beta-receptors. OT50, the time for onset of action, was 32.0 +/- 1.6 minutes. RT50, the time to achieve 50% recovery from maximal stimulation was, 393.0 +/- 20.2 minutes. We conclude that salmeterol stimulates PC secretion by type II cells through activation of beta-adrenergic receptors and has a longer duration of action (>6 hours) compared to other beta2-agonists. Salmeterol may be a useful drug with which to study the role of receptor desensitization in the developmental changes in PC secretion.
At 26 weeks of gestation, fetal tachyarrhythmias (about 250 bpm) and ascites were detected by ultrasonography, and oral treatment with propranolol (30 mg/day) was commenced. Within 10 h, the fetal heart rate changed to approximately 85 bpm. The averaged fetal magnetocardiogram triggered by R peaks showed P wave and QRS complexes and an extra P wave. In addition, many extra nonconducted P-waves were detected in a fetal direct electrocardiogram. At 27 weeks of gestation, fetal tachycardia occurred again, and arrhythmia was diagnosed as the result of a blocked premature atrial contraction (PAC) with intermittent atrial tachycardia by fetal electrocardiogram. Administration of transplacental propranolol (90 mg/day) resolved the fetal tachyarrhythmias and ascites. Further studies are required to evaluate the efficacy and adverse effects of propranolol for fetal atrial tachycardia.
To explore whether endogenous catecholamine participates in the effect of interleukin-2 on the isolated heart.
Propranolol appears to be a safe and effective treatment in the management of periorbital proliferating phase infantile hemangioma.
Reports of pharmaceuticals in STPs and aquatic systems in the northern hemisphere have surged over the last decade. However, the Australian evidence base is relatively limited, and information on the role of seasonal dilution in attenuation of micropollutants is also scarce. We investigated the removal of 11 PPCPs during sewage treatment in Australia's largest inland STP, and concentrations in the effluent-receiving environment under 2 dilution scenarios. Five treatment stages were sampled, as well as upstream and downstream of the effluent outfall in the Lower Molonglo/Upper Murrumbidgee Catchment, which is dominated by effluent flow during dry periods. Compounds of interest include carbamazepine (CBZ), venlafaxine (VEN), sertraline (SER), fluoxetine (FLX), atenolol (ATL), sotalol (SOT), metoprolol (MET) propranolol (PRL), chlorpheniramine (CHP), diphenhydramine (DPH), and triclosan (TCS). Removal of most pharmaceuticals in the STP was incomplete, although the degree of removal was highly variable for compounds in the same therapeutic class, and for the same compounds in different seasons. Removal efficiency was highest for TCS and lowest for VEN (effluent concentrations 5-7 times higher than influent). Influent mass loads and removal efficiencies of cardiovascular medicines varied considerably. Effluent loads were highest for CBZ, VEN and SOT in both seasons (up to 64 g/day). The dilution conditions were clearly reflected in the 'zone of impact' of PPCPs in the catchment. This study confirms that risk assessment models for PPCPs must account for seasonality of influent loads and removal efficiency of STPs, and site validation is critical for predictive capability. Seasonal dilution can play an important role in ameliorating potentially adverse effects related to mixtures of PPCPs in effluent-impacted systems.
Infantile cephalic and facial hemangiomas (IHs) are common and histologically benign vascular lesions in infants. This study investigates the clinical effect of using large doses of Propranolol for the treatment of IHs.