Journal of basic and clinical physiology and pharmacology
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J Basic Clin Physiol Pharmacol · Jan 2005
Single-dose ketamine administration induces apoptosis in neonatal mouse brain.
The activity of N-methyl-D-aspartate (NMDA) receptors is critical for neuronal survival in the immature brain. Studies have reported that chronic blockage of these receptors mediates apoptosis in neonatal animals. We investigated the apoptotic effect of a clinically relevant single dose of ketamine, an NMDA receptor antagonist, in the brain of neonatal mice. Seven-day-old ICR mice were injected with ketamine (1.25, 2.5, 5, 10, 20, and 40 mg/kg body weight, subcutaneously in 0.9% NaCl) or with 0.9% NaCl alone as control. Righting reflex testing was performed and mouse brains were examined at 24, 48, and 72 h and 7 days after injection. The number of degenerating neurons was measured using silver staining. Apoptosis was confirmed by DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). We observed in the sensorimotor cortex and cerebellum of ketamine-treated mice extensive apoptosis, which was clearly dose-dependent and present even after a low dose of ketamine (5 mg/kg). The most prominent apoptotic damage was detected 72 h post-injection (P < 0.001 vs control), at doses ranging from 10 to 40 mg/kg. After 7 d the number of neurodegenerative neurons, at doses ranging from 5 to 40 mg/kg, remained significantly high. The brain weight was comparable to that of untreated control mice and no gross neurobehavioral effects in the righting reflex test or alteration in the pattern of behavior was observed. The results indicate that the administration of ketamine in a clinically relevant single dose triggers long-lasting neuronal apoptosis in certain brain areas of neonatal mice. ⋯ The administration of ketamine in a clinically relevant single dose to 7-d-old mice induced apoptosis in the sensorimotor cortex and cerebellum. This effect was dose-dependent and long lasting.
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J Basic Clin Physiol Pharmacol · Jan 2003
Randomized Controlled Trial Clinical TrialIntramuscular administration of lidocaine or bupivacaine alters the effect of midazolam from sedation to hypnosis in a dose-dependent manner.
We examined the sedative/hypnotic interaction between the administration of intravenous (i.v.) midazolam and intramuscular (i.m.) lidocaine or bupivacaine. Women undergoing gynecological surgery (n = 150) were randomly assigned to 15 dose groups of 10 patients each. Fifty patients received one of five predetermined doses of midazolam for the calculation of its median effective dose (ED50). ⋯ The hypnotic ED50 for bupivacaine and lidocaine was 0.7 mg/kg (95% CI 0.5-1.0) and 3.32 mg/kg (95% CI 2.2-11.7), respectively. The slopes of the dose-response curves were significantly different (p < 0.01). Local anesthetics that are well within the range of clinical use for regional blocks or local infiltration can bring the effect of midazolam from the sedative into the hypnotic range.
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J Basic Clin Physiol Pharmacol · Jan 2001
Changes in effective and lethal doses of intravenous anesthetics and lidocaine when used in combination in mice.
We studied the interactions between a local anesthetic agent, lidocaine, and two general anesthetic drugs, propofol and ketamine, in mice. We used two end points: hypnosis, reflected by loss of the righting reflex, and death. ⋯ Probit and isobolographic analyses revealed supra-additive (synergistic) interactions between lidocaine and each of the other anesthetic agents regarding both the effective dose and the lethal dose. No significant difference was found between propofol and ketamine regarding the supraadditive effect.
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J Basic Clin Physiol Pharmacol · Jan 2000
The effects of midazolam and morphine on analgesic and sedative activity of ketamine in rats.
The aim of this study was to investigate possible interactions between the analgesic activity of ketamine (an N-methyl-D-aspartate antagonist), midazolam (a benzodiazepine derivative) and morphine using the tail-flick test in rats. Animals were treated s.c. with ketamine (1.0-10.0 mg/kg), midazolam (0.3 mg/kg), or morphine (0.6 mg/kg) alone. or in combination The strongest analgesic effect of ketamine was observed after 3.0 mg/kg. In higher doses no enhancement of ketamine activity were found. ⋯ The interaction of these two compounds with ketamine (5.0 mg/kg) occurred in a different manner, because midazolam led to a strong enhancement of ketamine analgesia. After morphine and ketamine (5.0 mg/kg) administration, very weak increase of ketamine analgesia was observed. The results of this study allow better understanding of the alteration of the analgesic effects of low doses of ketamine under the influence of morphine and midazolam.
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An understanding of auditory transduction in the ear can contribute to a better comprehension of the pathophysiological mechanisms which give rise to hearing loss. The incoming sound sets up a mechanical traveling wave which begins at the base and progresses along the basilar membrane, reaching a point of maximal displacement. The region of maximal displacement is a function of stimulus frequency. ⋯ This "electromotility" presumably provides mechanical feedback to the basilar membrane, augmenting its mechanical displacement. This is called the cochlear amplifier, providing the ear with improved sensitivity and frequency discrimination. Most forms of sensori-neural hearing losses (affecting the inner ear) are due to a lesion to some part of this cochlear amplifier (e.g. noise induced hearing loss, ototoxic drugs) and are therefore characterized by auditory threshold elevations and poorer frequency discrimination.