Lack of effect of antenatal glucocorticoid therapy in the fetal baboon on cerebral cortical glucose transporter proteins.

BACKGROUND: Maternal antenatal glucocorticoid therapy is used to accelerate lung maturation of immature babies at risk of preterm delivery. It acutely affects brain activity of the human fetus and reduces the immunoreactivity of neurocytoskeletal and synaptic proteins in the fetal baboon brain. These effects might be based on cerebral energy failure due to a decreased neuronal glucose uptake that has been shown in vitro. METHODS: Glucose uptake into the brain is selectively facilitated by GLUT1 expressed in the blood-brain barrier and GLUT3 expressed in the neuronal membrane. Immunohistochemical distribution of GLUT1 and GLUT3 were examined in the frontal neocortex of the fetal baboon brain at 0.73 gestation (i.e. similar to 28 weeks of human gestation) after maternal betamethasone administration, mimicking the clinical dose regimen. RESULTS: Betamethasone did not alter GLUT1 and GLUT3 immunoreactivity. CONCLUSIONS: The results suggest that inhibition of glucose uptake is not the mechanism for the cerebral effects of antenatal glucocorticoids.

Glucose transporter proteins GLUT1 and GLUT3 like immunoreactivities in the fetal sheep brain are not reduced by maternal betamethasone treatment.

Synthetic glucocorticoids administered to accelerate fetal lung maturation in threatened preterm delivery change electrocortical brain activity in the human and sheep fetus and alter structural neuronal proteins in fetal baboon and sheep. We hypothesized that these changes are due to a decreased amount of glucose transporter proteins (GLUT). Glucose uptake into cerebral neurons is selectively facilitated by glucose transporter protein GLUT1 in the blood brain barrier and GLUT3 in neuronal membranes. GLUT1 and GLUT3 immunoreactivity was examined in fetal sheep brain sections of the frontal neocortex, caudate putamen and hippocampus at 0.73 gestation after fetal exposure to betamethasone by direct fetal intravenous infusion or maternal intramuscular injections at the clinically relevant dosage. Betamethasone did not alter GLUT1 and GLUT3 immunoreactivity in any of the brain regions investigated, independently of the dose and route of administration. These data indicate that alteration of GLUT expression is unlikely to explain the cerebral functional effects of antenatal glucocorticoids.

Propofol anesthesia in spontaneously breathing children undergoing magnetic resonance imaging: comparison of two propofol emulsions.

BACKGROUND: This study evaluated a propofol-based anesthesia regimen with spontaneous breathing in pediatric patients scheduled for magnetic resonance imaging (MRI). METHODS: In this prospective, randomized, double-blind study propofol formulated with long-chain triglycerides (LCT) and mixed medium-chain/long-chain triglycerides (MCT/LCT) were used. Ninety patients aged 2.4 months to 7.3 years were premedicated with intravenous midazolam. Lidocaine was injected prior to propofol to reduce injection pain. Anesthesia was induced and maintained by propofol. Glycopyrronium bromide was administered for saliva reduction. Hemodynamics, blood oxygen saturation and endtidal capnography were continuously monitored. All patients received additional oxygen. The aggregated propofol dose for induction and maintenance of anesthesia was analyzed for therapeutic equivalence. Incidence of injection pain, laboratory safety values, vital signs, and the adverse event profile were analyzed to compare tolerability and safety. RESULTS: Propofol anesthesia was safe and successful in all children. Both propofol formulations were equivalent regarding dose requirements (mean induction and maintenance doses for anesthesia 2.0-4.0 mg.kg(-1) and 6.0-8.8 mg.kg(-1).h(-1) respectively; aggregated doses 8-13.26 mg.kg(-1)). There were no differences in drug safety such as hemodynamics, spontaneous breathing, injection pain, and laboratory values. Duration of induction and of recovery from anesthesia were short and all examinations were completed with minimal interruption. CONCLUSIONS: Propofol-based short-term anesthesia was well suited for anesthesia during MRI procedures in the studied pediatric patients. There were no clinically relevant differences between the two propofol formulations.

Comparison of the analgesic effects of a fixed-dose combination of orphenadrine and diclofenac (Neodolpasse) with its single active ingredients diclofenac and orphenadrine: a placebo-controlled study using laser-induced somatosensory-evoked potentials from capsaicin-induced hyperalgesic human skin.

OBJECTIVE: The aim of this study was to investigate the analgesic efficacy of Neodolpasse, a fixed-dose combination of orphenadrine and diclofenac, compared with those of its single active ingredients in a human pain model. METHODS: The study was designed as a randomised, double-blind, placebo-controlled, four-period crossover study. Twenty-four healthy female and male subjects received single infusions of Neodolpasse, orphenadrine, diclofenac or saline solution over 60 minutes. Infusions were separated by a 1-week washout period. Neurogenic inflammation and hyperalgesia were induced by topical occlusive application of a 1% capsaicin solution for 30 minutes on defined skin areas on the back. The pain response to CO2 laser pulses applied to the capsaicin-pretreated skin was measured by event-related vertex EEG recordings. This allowed us to study the influence of a single infusion on the central P2- and peripheral N1-components of laser-induced somatosensory-evoked potentials (LSEP) as a measure of pain response. RESULTS: Although none of the active treatments had a significant effect on the peripheral N1-component, all active treatments reduced the P2-component of the LSEP, reflecting central/spinal analgesic (anti-hyperalgesic) effects. These effects were statistically significant for orphenadrine (p < 0.0001) and for the combination of orphenadrine and diclofenac (p < 0.0013). The single ingredient diclofenac reduced the P2-component by a value just below clinical relevance (p < 0.0848). CONCLUSION: This study demonstrated the efficacy of Neodolpasse in a human pain model. The observed effect was mainly caused by central mechanisms and was found to be superior for the fixed-dose combination of orphenadrine and diclofenac compared with the individual ingredients. Both components contributed to the effect of the combination in an additive fashion, which can be explained by the different molecular mechanisms of action of each drug.