Pre/post effectiveness evaluation of updated additional risk minimisation measures for an orphan disease: Myozyme (alglucosidase alfa) Safety Information Packet.

Background: The alglucosidase alfa (Myozyme®) Safety Information Packet ("previous SIP") was updated to improve readability and content ("updated SIP"). We compared the previous and updated SIPs.

Methods: A two-wave pre-post multicountry survey was conducted among health care professionals (HCPs) who prescribed or monitored patients on alglucosidase alfa in the largest European Union ("EU5") countries and Poland.

Neuroprotective effect of gacyclidine. A multicenter double-blind pilot trial in patients with acute traumatic brain injury.

The aim of this study was to assess the safety and efficacy of intravenous (IV) injections of gacyclidine, a novel NMDA receptor antagonist, for neurological and functional recovery following acute traumatic brain injury. This multicenter, prospective, randomized, placebo-controlled, double-blind study compared four parallel groups. Two IV doses were administrated (placebo, 2x0.

Pharmacokinetics of gacyclidine enantiomers in plasma and spinal cord after single enantiomer administration in rats.

The purpose of this study was to determine the pharmacokinetics of gacyclidine, a non-competitive NMDA antagonist, in plasma and spinal cord extracellular fluid (ECF) after IV administration of single enantiomers in rats. After implantation of microdialysis probes in spinal cord, concentrations in plasma and ECF dialysates were determined by a chiral GC/MS assay over 5 h after administration of either (+)-gacyclidine or (-)-gacyclidine (1.25 mg/kg).

Efficacy of a new neuroprotective agent, gacyclidine, in a model of rat spinal cord injury.

Prevention of the immediate excitotoxic phase occurring in response to spinal cord injury (SCI) is a major issue to reduce the neuronal damage responsible for any ensuing motor deficits. The present study evaluated the neuroprotective efficacy of three noncompetitive NMDA receptor antagonists: Gacyclidine (GK-11), a new compound, Dizocilpine (MK-801), and Cerestat (CNS-1102) in a rat spinal cord contusion model. To mimic human SCI, a standardized model of rat spinal cord closed contusion in which animals spontaneously and progressively recover from the induced paraplegia was employed.

Distribution of gacyclidine enantiomers after experimental spinal cord injury in rats: possible involvement of an active transport system.

The pharmacokinetics of gacyclidine enantiomers, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were studied in plasma and spinal cord extracellular fluid (ECF) after experimental spinal cord injury in rats. Spinal cord trauma was produced by introducing an inflatable balloon in the dorsal subdural space. Upon implantation of microdialysis probes in spinal cord (T9) and intravenous (iv) bolus administration of (+/-)-gacyclidine (2.

Neuroprotective effects of a novel NMDA antagonist, Gacyclidine, after experimental contusive spinal cord injury in adult rats.

The aim of this study was to analyze the optimal time-window for neuroprotection by a novel NMDA antagonist, Gacyclidine, after experimental spinal cord injury, in terms of its functional, histopathological and electrophysiological effects. This molecule has already demonstrated its capacity for reducing the extent of an ischemic lesion and is currently experimented in a clinical trial of spinal cord injury. In this study, the spinal cord of rats was damaged by a contusive method and the animals were treated by saline or 1 mg/kg of Gacyclidine i.

Distribution of gacyclidine enantiomers in spinal cord extracellular fluid.

Purpose: Determination of the pharmacokinetics of gacyclidine enantiomers, a non-competitive NMDA antagonist, in plasma and spinal cord extracellular fluid (ECF) of rats.

Methods: Implantation of microdialysis probes in spinal cord (T9). Serial collection of plasma samples and ECF dialysates over 5 hours after IV bolus administration of (+/-)-gacyclidine (2.

Sensitive gas chromatographic-mass spectrometric method for the determination of gacyclidine in rat plasma and spinal cord dialyzates.

A sensitive gas chromatographic-mass spectrometric (GC-MS) procedure is described for the selective determination of gacyclidine (a non-competitive N-methyl-D-aspartate antagonist) in rat plasma and spinal cord dialyzates. It involves a single-step liquid-liquid extraction of plasma samples and dialyzates with hexane (pH 8.0) and the use of phencyclidine as an internal standard.

Neuroprotective effects of gacyclidine after experimental photochemical spinal cord lesion in adult rats: dose-window and time-window effects.

The aim of this study was to evaluate the efficacy, optimal dose, and optimal time-window of gacyclidine, a novel N-methyl-D-aspartate (NMDA) receptor antagonist, in terms of its functional, histopathological, and electrophysiological effects after experimental spinal cord injury. The spinal cord of rats was damaged by a photochemical method and the animals were treated by saline or gacyclidine at doses of 1, 2.5, or 5 mg/kg 10 min after injury or gacyclidine 1 mg/kg 10, 30, 60, and 120 min after injury.

Modified gas chromatographic-mass spectrometric assay for the determination of gacyclidine enantiomers in human plasma.

A modified method for the determination of gacyclidine enantiomers in human plasma by GC-MS with selected-ion monitoring using the deuterated derivative of gacyclidine (d3-gacyclidine) as internal standard was developed. Following a single-step liquid-liquid extraction with hexane, drug enantiomers were separated on a chiral fused-silica capillary column (CP-Chirasil-Dex; Chrompack). The fragment ion, m/z 266, was selected for monitoring d3-gacyclidine (retention times of 35.

Determination of gacyclidine enantiomers in human plasma by gas chromatography-mass spectrometry using selected-ion monitoring.

A sensitive gas chromatographic assay using mass selective-detection has been developed for the simultaneous quantitation of the enantiomers of (+/-)-gacyclidine (a non competitive N-methyl-D-aspartate antagonist) in human plasma. Gacyclidine enantiomers and phencyclidine (PCP), the internal standard, were extracted using a single-step liquid-liquid extraction with hexane at pH 8.0.

Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced oxidative stress in patients undergoing coronary bypass surgery.

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract with potent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention.

Effect of Ginkgo biloba extract (EGb 761) on the vasospastic response of mouse cutaneous arterioles to platelet activation.

The effect of intravenously administered Ginkbo biloba extract (EGb 761) on the vasospastic response to platelet activation has been assessed using a cutaneous flap preparation in anaesthetized mice. Arterioles of the axillary artery were observed by intravital microscopy, and platelets were activated by topical application of ADP under two steady state conditions: normothermia (37 degrees C) and hypothermia (24 degrees C). Responses of the cutaneous arterioles to stimulation by topical application of a thromboxane agonist (U46619) were also compared in animals treated intravenously with EGb 761 or with a thromboxane synthesis inhibitor (U63557).

EGb 761 in control of acute mountain sickness and vascular reactivity to cold exposure.

Method: We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract (EGb 761) on acute mountain sickness (AMS) and vasomotor changes of the extremities during a Himalayan expedition. After giving their written informed consent, the subjects were randomized to two groups. One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo.

Protection of polyunsaturated fatty acids against iron-dependent lipid peroxidation by a Ginkgo biloba extract (EGb 761).

Iron can induce a peroxidative degradation of the membrane polyunsaturated fatty acids by the well-known Fenton reaction. Chelated iron can also form a complex with oxygen, called perferryl ion, which is able to induce lipoperoxidation without a detectable production of hydroxyl radicals. The antioxidant properties of a titrated and standardized extract of Ginkgo biloba leaves (EGb 761) against iron-dependent peroxidative degradation of the membrane polyunsaturated fatty acids were studied.

Ascorbyl free radical: a noninvasive marker of oxidative stress in human open-heart surgery.

To assess the development of oxidative stress in cardiac ischemia/reperfusion, the resulting depletion of plasma ascorbate was monitored by electron spin resonance spectroscopic detection of ascorbyl free radical (AFR) in a homogeneous group of 12 patients undergoing aortic valve replacement. Dimethyl sulfoxide (DMSO) was used as an enhancer and stabilizer for AFR in plasma separated from blood samples collected 15 min before incision, 10 min before aortic declamping, and sequentially during the initial 30 min of reperfusion. Plasma DMSO/AFR levels of patients were found to be significantly lower than in healthy subjects (-25%), further decreased upon ischemia (-35%), dropped to their lowest values within the first 10 min of reperfusion (-46%), and did not recover their initial values within 30 min following reflow.

Effect of two doses of ginkgo biloba extract (EGb 761) on the dual-coding test in elderly subjects.

The subjects of this double-blind study were 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment. In a crossover-study design, each subject received placebo or an extract of Ginkgo biloba (EGb 761) (320 mg or 600 mg) 1 hour before performing a dual-coding test that measures the speed of information processing; the test consists of several coding series of drawings and words presented at decreasing times of 1920, 960, 480, 240, and 120 ms.