Biomedical subjects

Ronald W Wood

Publications and source records attributed to Ronald W Wood.

2 recordsLinked to original sources

PubMed2003

Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate.

Methylecgonidine is formed from cocaine base when smoked and has been identified in biological fluids of crack smokers. Ecgonidine, a metabolite of methylecgonidine formed via esterase activity, also has been identified in similar samples collected from crack smokers. Methylecgonidine and ecgonidine can be used as biomarkers to differentiate smoking from cocaine use via other routes of administration. We determined the pharmacokinetic properties of methylecgonidine and ecgonidine in sheep after intravenous administration of methylecgonidine at doses of 3.0, 5.6, and 10.0 mg/kg using gas chromatography-mass spectrometric assays. Methylecgonidine clears quickly from blood with a half-life of 18 to 21 min, whereas ecgonidine has a longer half-life of 94 to 137 min. Because ecgonidine clears more slowly, it may be a more effective biomarker of cocaine smoking. The cardiovascular stimulant effects of cocaine contrast with reported in vitro muscarinic agonist effects of methylecgonidine, decreasing contractility and stimulating nitric oxide production in cardiac cells and tissues. To test the hypothesis that methylecgonidine produces cardiovascular effects in vivo consistent with muscarinic agonism, methylecgonidine was administered to sheep intravenously (0.1-3.0 mg/kg) while monitoring heart rate and blood pressure. Significant hypotension and tachycardia occurred in all three sheep. Two of the three sheep demonstrated mild bradycardia 3 to 5 min after methylecgonidine injection. Intravenous pretreatment with atropine methyl bromide (15 microg/kg) antagonized methylecgonidine-induced hypotension in all three sheep, supporting the hypothesis that methylecgonidine acts as a muscarinic agonist in vivo.

Animals↗

PubMed2002

Continuous bladder infusion methods for studying voiding function in the ambulatory mouse.

OBJECTIVES: To develop a method for chronic cannulation of the mouse bladder that would enable repeated intravesical drug delivery and measurement of voiding patterns in unrestrained mice under controlled infusion conditions. METHODS: Fifteen female mice were anesthetized with halothane and implanted with a 3F polyurethane bladder catheter. The catheter exited from the back through mesh and a polysulfone button into a spring coil that protected the catheter and tethered the mouse. A counterbalanced swivel and infusion pump permitted unencumbered mobility during continuous intravesical perfusion. RESULTS: Patent catheterization was consistently achieved for at least 5 weeks. The voiding patterns produced with an infusion pump were stable not only within a study session but also during the course of several weeks. The catheters remained patent but eventually withdrew from the bladder in 9 mice, at which point the mice were killed. The mesh eventually emerged from the skin in 4 animals without evidence of infection and was associated with catheter leakage at the level of mesh exposure. The subcutaneous placement of the mesh and tether assembly adequately transferred torque to the swivel without catheter obstruction. One mouse died unexpectedly during anesthesia; another was killed 1 week after catheter implantation because of an intraperitoneal leak. No bladder stones were identified. The results of the urine cultures were inconclusive. CONCLUSIONS: Continuous, patent catheterization of the murine bladder can be achieved consistently for a period of 5 weeks. When used in combination with counterbalanced swivel assemblies and electronic balance technology, these methods permit prolonged evaluation of micturition patterns in the awake, ambulatory mouse.

Administration, Intravesical↗