1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
This study aims to make an account of the children born following transplantation of frozen-thawed ovarian tissue worldwide with specific focus on the perinatal outcome of the children. Furthermore, perinatal outcome of seven deliveries (nine children) from Denmark is reported.
PubMed was searched for papers of deliveries resulting from ovarian tissue cryopreservation (OTC). Seven women underwent OTC prior to chemotherapy. Four of these women still had low ovarian function and had tried to conceive. They therefore had tissue autotransplanted to augment their fertility. The other three women had developed premature ovarian insufficiency (POI) after the end of treatment.
Worldwide, approximately 95 children have been born or will be born in the near future from OTC, including these 9 new children. Information on the perinatal outcome was found on 40 children. The mean gestational age was 39 weeks and the mean birth weight was 3168 g of the singleton pregnancies, which is within internationally recognized normal standards. Furthermore, half the singletons resulted from natural conception and all twins resulted from in vitro fertilization treatment. All seven Danish women became pregnant within 1-3 years after transplantation. They gave birth to nine healthy children.
The data is reassuring and further suggests that cryopreservation of ovarian tissue is becoming an established fertility preservation method. The seven Danish women reported in this study were all in their early thirties when OTC was performed. Most other reported cases were in the women's twenties. This suggests that the follicular pool in the thirties is large enough and sufficient to sustain fertility.
Our primary goal has been to discover leukotriene biosynthesis inhibitors with characteristics that are appropriate for use as clinical agents. The success of the use of zileuton in the treatment of asthma led us to explore further the use of the N-hydroxyurea class of 5-lipoxygenase inhibitors as longer-acting compounds with good lung penetration. A variety of in vitro and in vivo methods were used to evaluate a large number of compounds, from which ABT-761 [(R)-N-(3-(5-(4-fluorophenylmethyl)thien-2-yl)-1-methyl-2-pr opynyl)-N-hydroxyurea] was selected for study. ABT-761 exhibited potent and selective inhibition of leukotriene formation both in vitro and in vivo. More importantly, the compound potently inhibited antigen-induced bronchospasm in guinea pigs when given either prophylactically or therapeutically. In addition, ABT-761 was a potent inhibitor of eosinophil influx into the lungs of Brown Norway rats. These data provide added support for the role of leukotrienes in both bronchospasm and eosinophilic inflammation and characterize ABT-761 as a particularly potent inhibitor of leukotrienes formed in pulmonary tissues. These data combined with the excellent pharmacokinetic characteristics of the compound indicate its potential use in the treatment of leukotriene-dependent human disease.
The hemodynamic and metabolic effects of acetate were studied in rats in vivo and in the isolated perfused heart. Hemodynamic parameters, myocardial phosphagens, inorganic phosphate, and adenosine were measured in vivo. Acetate uptake, coronary flow, O2 consumption, parameters of the cellular energy state, and hypoxanthine compounds and their washout were measured in heart perfusion experiments. Heart rate (HR), cardiac output, and the peak derivative of the left ventricular pressure rise (dP/dtmax) increased significantly during acetate infusion in vivo, but mean arterial pressure, systolic arterial pressure, and systemic vascular resistance decreased. Heart muscle ATP concentrations decreased after 7 min of acetate infusion. In vivo cardiac work load (HR.(peak left ventricular pressure] showed a positive correlation with tissue adenosine concentration and a negative correlation with phosphorylation potential. Acetate uptake in the perfused hearts was about 2.5 mumol/min per gram wet weight. Acetate perfusion increased O2 consumption and coronary flow concomitantly with a decrease in tissue ATP concentration. Tissue AMP and perfusate effluent adenosine concentration and adenosine output increased significantly, perfusate adenosine showing a non-linear positive correlation with coronary flow. The results demonstrate that acetate induces considerable changes in hemodynamics and metabolism in the heart.
Intravenous injection of the selective mu-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages. In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusion in vitro. Furthermore, stimulation of mu-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe2+ and ascorbic acid.
To assess the possibility of stimulating Ca2+-activated K+ channels, marine fish erythrocytes were incubated at 20-22 degrees C in saline containing a Ca2+-ATPase inhibitor (orthovanadate), a Ca2+ ionophore (A23187), propranolol or Pb2+. Incubation of the cells for up to 2 h under control conditions or in the presence of 5 mM NH4VO3 and 1 mM Ca2+ did not affect the intracellular K+ and Na+ concentrations. About 50% cellular K+ was lost from erythrocytes incubated in the presence of 0.01 mM A23187, 1 mM EGTA and 0.4-1.0 mM Ca2+. There was a significant loss of cellular K+ after the addition of 0.05-0.2 mM propranolol to the incubation medium. The stimulatory effect of propranolol on the K+ efflux was independent of external Ca2+. Blockers of Ca2+ transport, verapamil and Co2+, caused only a small decrease in the K+ loss induced by propranolol. The treatment of erythrocytes with 1-2 microM Pb2+ led to a minor K+ loss, but at a Pb2+ concentration of 20-50 microM, about 70% cellular K+ was lost. The K+ efflux induced by propranolol or Pb2+ was completely blocked by 1 mM quinine. The induced K+ loss from the erythrocytes was accompanied by a slight increase in the intracellular Na+ concentration. These data indicate the possibility of inducing Ca2+- and Pb2+-activated potassium channels in erythrocytes of S. porcus. A distinctive feature of the cells is a high sensitivity to propranolol, which activates K+ channels in the absence of external Ca2+.