Zopiclone versus diazepam effects on EEG power maps in healthy volunteers

AIMS: The aim of this study was to compare the effects of aspirin on platelet function as measured by the 'classical' template bleeding time with a new ex vivo method measuring closure times using the PFA-100 machine. Platelet aggregation in response to arachidonic acid was also measured ex vivo. METHODS: The trial was a randomized, double-blind, placebo-controlled crossover design, with each volunteer taking 750 mg aspirin (BP) or placebo, three times a day for 5 days, with an 18 day wash-out period between treatments. Bleeding times and closure times were measured before the first dose on the first day and 0.5 h after the last dose on the fifth day of each treatment period. They were also measured 2 weeks after the last day of the trial. RESULTS: Baseline bleeding times (pre-placebo) were 415 s using the Simplate, whilst baseline closure times were 115 s using the PFA-100. Aspirin treatment caused an increase of both the template bleeding time (61%) and the closure time of the PFA-100 (79%) when compared with the effects of placebo. The platelet aggregatory response to arachidonic acid was completely inhibited following aspirin treatment and was unaffected following placebo. Two weeks after the end of the trial, all values had returned to pre-treatment levels. The template bleeding time was unaltered in 1 of the 12 volunteers during aspirin treatment and was significantly prolonged in 3 of the 12 volunteers during placebo treatment. The PFA-100 closure time was unaltered in 1 of the 12 volunteers during aspirin treatment and was prolonged in 1 subject during placebo treatment. CONCLUSIONS: The change in closure time using the PFA-100 is as sensitive and reproducible to the effects of aspirin on platelet function as is the template bleeding time test. However, the PFA-100 produced less variable effects with fewer false positive results.     

EEG pharmacodynamics upon single administration of seduxen in healthy volunteers

We have examined the type I collagen protein, RNA, and cDNA of 2 children with moderately severe (type IV) osteogenesis imperfecta (OI). They have in common a non-lethal form of OI with ambulatory potential, overmodification of type I collagen protein, and a substitution of serine for glycine in the collagen chain produced by one alpha 1(I) allele. The first child (Marini et al.: J Biol Chem 264:11893-11900, 1989) is now 7 years old, with the height of a 3-year-old. Her course includes significant remodeling of lower long bones and 4 femur fractures. She walks independently. A mishmatch was detected in her alpha 1(I) mRNA using RNA/RNA hybrids; it was demonstrated to be due to a G-->A point mutation in one allele of alpha 1(I), resulting in the substitution of serine for glycine 832. The second child is now 6 1/2 years old, with the height of 1 1/2-year-old. Her history includes significant bowing of femurs and tibias, 6 femur fractures, S-curve scoliosis, compression of all lumbar vertebrae, and limited short-distance walking with braces. Her alpha 1(I) mRNA has also been studied by RNA hybrid analysis; there is a single G-->A change in one alpha 1(I) allele causing the substitution of serine for gly 352. Both children have moderately severe OI. However, the serine substitution at gly 352 is associated with a more severe phenotype then is the serine substitution at gly 832. Compared to substitutions described in other cases of OI, the serine 352 is located in the middle of a cluster of cysteine substitutions associated with non-lethal OI.(ABSTRACT TRUNCATED AT 250 WORDS)     

A dose proportionality study of eprosartan in healthy male volunteers

BACKGROUND: Previous investigations in BALB/c strain mice have revealed that, after skin sensitization, draining lymph node cells (LNC) produce high levels of interleukin 6 (IL-6) and that the secretion of this cytokine correlates closely with the proliferative activity of LNC. The main source of IL-6 within draining lymph nodes was found to be dendritic cells (DC), most of which derive from epidermal Langerhans cells. OBJECTIVE: To explore further the relationship between DC-derived IL-6 production in lymph nodes, LNC proliferative activity, and the development of contact sensitization, comparisons between BALB/c and C3H/HeN strains of mice have been conducted. METHODS: Contact sensitizing potential was measured in both strains of mice as a function of lymphocyte proliferative responses (assessed by the incorporation of radiolabelled thymidine) and challenge-induced increases in ear thickness. The concentration of IL-6 in skin homogenates and the production of IL-6 by allergen-activated LNC were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In both strains of mouse, topical exposure to oxazolone, a potent contact allergen, induced a vigorous proliferative response by draining LNC and the development of skin sensitization. However, under these conditions of exposure, activated LNC prepared from mice of C3H/HeN strain failed to secrete substantial amounts of IL-6, the levels of this cytokine being on average some 20- to 40-fold less than those measured in BALB/c mice. The failure of LNC from C3H/HeN mice to secrete comparable levels of IL-6 was not attributable to a reduced ability of DC to accumulate in draining lymph nodes after skin sensitization. Nor did reduced IL-6 secretion by C3H/HeN LNC reflect a systemic inability to elaborate this cytokine. Epicutaneous exposure of C3H/HeN mice to oxazolone resulted in the induction of cutaneous IL-6 at levels similar to, or greater than, those observed after identical treatment of BALB/c strain mice. CONCLUSIONS: The conclusion drawn is that there does not exist a universal association between IL-6 production in draining lymph nodes and the vigor of proliferative responses by LNC. Further, cutaneous immune responses and skin sensitization may proceed apparently normally in the absence of high levels of IL-6 production by lymph node cells.     

The effects of age and gender on the single dose pharmacokinetics of avitriptan administered to healthy volunteers

The effects of age and gender on the single dose pharmacokinetics of avitriptan and its three metabolites were assessed in 15 young men, 15 young women, 15 elderly men and 15 elderly women. Avitriptan was administered as a 150-mg capsule after a 10-hour fast and serial plasma and urine samples were collected up to 36 hours after the dose. Plasma samples were analyzed for avitriptan and its metabolites, N-desmethyl avitriptan (ND048), O-desmethyl avitriptan (OD048), and methoxypyrimidinyl piperazine (MPP). Urine samples were analyzed for only avitriptan and MPP. Avitriptan was well tolerated in all four groups. The drug was rapidly absorbed with a median time to maximum plasma concentration (tmax) between 0.5 and 1.5 hours. No significant gender-related differences were found in the maximum plasma concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUC0-infinity) of avitriptan. Renal clearance of avitriptan was significantly smaller in young women compared with young men, but this is clinically not relevant because only 2% to 3% of the total dose is excreted unchanged. Compared with the young volunteers, mean Cmax was approximately 50% higher in the elderly but there was no difference in the AUC0-infinity between the 2 age groups. Plasma concentrations of ND048, OD048, and MPP were each 50 to 100 fold lower than those of avitriptan. Hence some age- and gender-related differences found in the pharmacokinetics of avitriptan metabolites are probably not relevant in the assessment of overall safety and efficacy of avitriptan. Based on the pharmacokinetics and tolerability, no age or gender-related dose adjustment is necessary for avitriptan.     

Comparative bioavailability of two atenolol tablet formulations in healthy male volunteers after a single dose administration

The bioavailability of 2 atenolol tablet formulations (Angipress from Laboratórios Biosintética, and Atenol from Wellcome ICI Laboratory, Brazil) were compared in 18 healthy male volunteers who received a single 50 mg dose of each atenolol formulation. The study was conducted following an open randomized 2-period crossover design with a 14-day washout interval between doses. Plasma samples were obtained over a 24-hour interval and atenolol concentrations were determined by HPLC with fluorimetric detection. From the plasma atenolol concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(zero-24) (area under the concentration vs time curves from 0-24 h), ke (terminal elimination constant), t1/2 (terminal first order elimination half-life), AUC (area under the concentration vs time curves extrapolated to infinity), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and Cmax/AUC. All these variables were analyzed using both parametric and nonparametric statistics. Geometric mean Angipress/Atenol individual percent ratios were 99.6% for AUC(zero-24), 99.7% for AUC, 98.0% for Cmax, 102.8% for t1/2, 97.2% for ke and 97.8% for Cmax/AUC, with all their 90% confidence intervals within the bioequivalence range 80-125%, thus showing similar patterns of absorption and disposition. Arithmetic mean for individual Tmax differences was 0.8 h, and the 90% confidence interval did not include the zero value. Based on these results and in accordance with the European Union and the US Food and Drug Administration bioequivalence requirements we conclude that both atenolol formulations are bioequivalent for both the extent and the rate of absorption.     

Memory and psychomotor effects of oxcarbazepine in healthy human volunteers

Cognitive and psychomotor impairments can be unwanted adverse effects of antiepileptic drugs. The present double-blind, cross-over study with healthy volunteers was designed to assess the effects of two doses of oxcarbazepine (OXCZ) (150 mg b.i.d.; 300 mg b.i.d.) and a placebo, each given over a two week period. Twelve subjects completed a battery of tests before and 4 h after morning doses on days 1, 8 and 15. Results of objective tests indicated that OXCZ improved performance on a focussed attention task and increased manual writing speed. Subjective ratings showed OXCZ increased feelings of altertness, clear-headedness and quickwittedness. OXCZ had no effect on the range of long-term memory processes assessed in this study. It is concluded that at the doses employed, OXCZ has a slightly stimulant effect on some aspects of psychomotor functioning.     

Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers

The pharmacokinetics of iron were investigated after intravenous administration to 12 healthy volunteers of iron(III)-hydroxide sucrose complex (Venofer) as a single i.v. dose containing 100 mg Fe. The average predose concentration was 35.7 +/- 12.5 mumol/l. There was no statistically significant difference between the serum iron level before injection (0 h) and the level at 24 h after the injection. The compartment model used includes a Michaelis-Menten term and is in excellent agreement with the observed exchange of iron to transferrin and with the daily iron turnover by transferrin. The intravenously injected iron(III)-hydroxide sucrose complex led rapidly to high serum iron levels. Maximum measured levels averaged 538 mumol/l (30.0 mg/l) at 10 min after the injection. The terminal half-life of the injected iron was calculated to be 5.3 h. Mean total area under the curve (AUC) was 1491 mumol/l h, the mean residence time (MRT) was 5.5 h. The total body clearance was 20.5 ml/min. The volume of distribution of the central compartment (Vc) was 3.21, hence close to the volume of the serum; the volume of distribution at steady state (Vdss) was 7.31; and the volume of distribution during elimination (Vdarea) was 9.21. The calculated amount of iron transported by transferrin was 31.0 +/- 6.6 mg Fe/ 24h. In summary, the data show that the injected iron(III)-hydroxide sucrose complex is quickly cleared from the serum with a terminal half-life of approximately 5-6 h. Renal elimination of iron contributed very little to the overall elimination (in average < 5%). Renal elimination of sucrose averaged about 68 +/- 10% and 75 +/- 11% of the administered dose after 4 h and 24 h, respectively.     

The haemodynamic effects and pharmacokinetics of intravenous nicorandil in healthy volunteers

Psychotherapy research with children is based mainly on adult methodologies. Common issues include bias in recruitment of subjects, demographics, developmental concerns, and control group considerations. The advantages and drawbacks of various types of control groups, such as wait-list controls, and placebo conditions are discussed along with ethical issues. Instrument choice, validity and reliability, and standardization of procedures in conducting research are addressed. Finally, the therapist as a variable is reviewed, including selection and assignment of therapists, and therapist bias.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1-antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

EEG spectral analysis of caffeine effects

Spectral EEG analysis is shown to quantify the centrally stimulating effects of caffeine. Comparing the effects of coffee, decaffeinated coffee, caffeine solution and placebo results in two groups of substances: coffee and caffeine solution on one side, decaffeinated coffee and placebo on the other. The within-group differences are negligible, whereas the between-group differences are highly significant. It may be concluded that caffeine is the effective factor. This study gives no valid evidence confirming possible effects of other coffee ingredients.     

The effects of exogenous epinephrine on a convulsive dose of lidocaine: relationship with cerebral circulation

A decision tree for the diagnosis of FNAB was derived from defined human observations using a rule induction method, C4.5 (a derivative of the ID3 algorithm). This algorithm is an implementation of the top-down induction method where the tree is determined iteratively by adding those nodes and branches which maximize the information gain at each step. The tree was derived from a training set of 200 FNAB with known outcome using 10 defined features (from one observer) and patient age. The tree contained a total of seven nodes (six observable features and patient age) with eight endpoints (four benign, four malignant). The tree was applied to a test set of 400 further FNAB with observations from the training observer and produced a sensitivity of 95%, specificity of 93% and a positive predictive value (PPV) of a malignant result of 89%. Four trainee pathologists were given a training session on the observable features and then used the tree to determine outcome in a further 50 FNAB. The observers were blind to clinical details apart from age and the endpoints were coded with letters and not labelled benign or malignant. The results from these observers produced ranges of sensitivity 80-96%, specificity 64-92%, PPV 73-92% and kappa statistics (with known outcome) 0.6-0.8. Reported difficulties in using the tree included estimation of nuclear size. These results were worse than the performance of the observers on a further 50 cases without using the decision tree (sensitivity 80-100%, specificity 72-100%, PPV 78-100%, kappa 0.72-0.92). The original 50 case test set was rerandomized and the four trainee observers made all 10 defined observations on each specimen without using the decision tree; these observations were then used to derive decisions from the tree. The performance from this method was similar to that using selected features from the tree, suggesting that observation of all features together does not improve the reliability of each specific observation. The poor performance of this tree suggests that this methodology may be unsuitable for producing decision support aids for diagnostic or training purposes in this domain.     

Cold water immersion modulates the reinforcing effects of nitrous oxide in healthy volunteers.

The purpose of this study was to determine if a contextual variable manipulation, water temperature of a bath in which a forearm was immersed, would modulate the reinforcing effects of nitrous oxide (N?O) in healthy volunteers (N?=?12). Each of 2 separate choice experiments consisted of a lukewarm water session and a cold water session. Each session consisted of 3 trials: The 1st 2 were sampling trials in which participants inhaled either 100% oxygen or 40% N?0 for 25 min, and the last trial was a 25-min choice trial, in which participants chose between the 2 agents. In each of the 3 trials, participants immersed their forearm in either ice-cold or lukewarm water for 3 min. A variant of the McNemar test revealed that participants were more likely to choose N?O on cold water sessions than on warm water sessions. The authors conclude that N?O was more reinforcing when participants forearms were immersed in ice-cold water than when immersed in lukewarm water. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between the dose of lidocaine administered endotracheally in small children and the serum lidocaine level--recommended dose prior to endotracheal intubation

To determine the optimum dose of lidocaine administered in the trachea prior to endotracheal intubation, we divided 102 surgical patients 3-5 years of age into 3 groups, i.e., group 1; 1 mg.kg-1 was sprayed in the trachea, group 2; 2 mg.kg-1 was sprayed in the trachea, group 3; 1 mg.kg-1 was sprayed in the trachea, and 1 mg.kg-1 in the pharynx and the oral cavity simultaneously. The venous serum concentration of lidocaine was measured two times either 1.5, 3, 5, 10, 15, 20, 30 or 45 min after the spray in each case. In group 1, the mean concentration of lidocaine reached the maximum of 1.05 micrograms.ml-1 at 5 min and decreased gradually after that with a small inter-individual variation. In group 2, after reaching the mean maximum concentration of 3.51 micrograms.ml-1 at 3 min, the serum level dropped quickly and then gradually decreased. There were a few cases where serum level was over 7 micrograms.ml-1. In group 2, after reaching the mean maximum concentration of 1.38 micrograms.ml-1 at 5 min, the serum level decreased more slowly, suggesting a slow absorption from the pharynx and/or the oral cavity. We conclude that the recommended dose of lidocaine for endotracheal administration is less than 2 mg.kg-1.     

Pharmacodynamic comparison of the acute effects of nomifensine, amphetamine and placebo in healthy volunteers

In a double blind cross over trial the effects of single doses of 100 mg nomifensine, 15 mg racemic amphetamine and placebo were compared in 9 healthy volunteers. Assessments of choice reaction behavior, simple reaction time, critical flicker fusion and attention on continuous calculations were performed together with a series of self rating scales, a side-effect list and vital signs before and 90 min., 180 min. and 360 min. after each administration. While the only significant nomifensine effect was an increase of correct solutions in the continuous calculation task, amphetamine differed from nomifensine and placebor in a number of subjective variables which describe emotional changes typical for drug stimulation. Subjects also expressed the will to have amphetamine prescribed for fatigue and loss of drive, whereas preferences for nomifensine were virtually the same as for placebo. Under amphetamine heart rate and blood pressure were increased and side-effects were frequent. It is concluded that nomifensine showed none of those subjectively pleasant amphetamine effects which are responsible for the reinforcement function leading to amphetamine dependence.     

The assessment of residual effects of a single dose of diazepam on visually-defined EEG patterns

Patients with medically intractable trigeminal neuralgia characterized by paroxysmal, triggered, trigeminally distributed pain are excellent candidates for neurosurgical intervention, which can not only relieve the pain of trigeminal neuralgia, but also eliminate the unpleasant side effects of medicines used to treat it. The two major neurosurgical choices are percutaneous denervation and microvascular decompression (MVD). Percutaneous denervation is done best when the surgeon has available radiofrequency and glycerol and uses one, the other, or both depending on technical circumstances that pertain to each patient. The percutaneous denervation is less likely than MVD to cause death, stroke, facial weakness, or hearing loss, but more likely to be associated with recurrence or dysesthesias. Patients with multiple sclerosis, medical illness, or who are elderly are much better candidates for percutaneous denervation. For any patient, a number of other factors also must be considered before deciding on a particular procedure. These include response to previous interventions, ability to tolerate carbamazepine, risk tolerance for various complications, preference regarding duration of hospital stay and postoperative recovery, presence of pain outside the trigeminal distribution, and findings on a high resolution magnetic resonance imaging (MRI) scan.     

Urinary excretion and bactericidal activities of a single oral dose of 400 milligrams of fleroxacin versus a single oral dose of 800 milligrams of pefloxacin in healthy volunteers

Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin, N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects' urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 microgram/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 micrograms/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true for Enterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.     

The effects of transnasal butorphanol on mood and psychomotor functioning in healthy volunteers

Transnasal butorphanol is effective in relieving migraine and postoperative pain. The extent to which this drug preparation impacts on cognitive and psychomotor performance, as well as mood, has not been examined. Accordingly, the cognitive and psychomotor, subjective, and physiological effects of two clinically relevant doses of transnasal butorphanol (1 and 2 mg) were compared to that of placebo, and a common analgesic drug combination given for pain relief in ambulatory settings, 600 mg of acetaminophen and 60 mg of codeine, in healthy volunteers (n = 10). The larger transnasal butorphanol dose impaired psychomotor performance for up to 2 h, and produced subjective effects for up to 3 h. The smaller dose had no psychomotor-impairing effects, but had subjective effects (including increased ratings of "sleepy"). All three active drug conditions including miosis. These laboratory results suggest that patients should use caution when using the 1-mg dose of transnasal butorphanol, and should curtail certain activities if they administer the 2-mg dose of transnasal butorphanol for analgesia.     

Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers.

Benzodiazepines and alcohol are widely used psychoactive substances that have performance-impairing effects. Research suggests that the impairment profiles for benzodiazepines and alcohol differ, although few cognitive psychopharmacological studies have directly compared these drugs. This double-blind, double-dummy, placebo-controlled, repeated measures study directly compared the acute dose effects of triazolam (0.125, 0.25 mg/70 kg) and alcohol (0.40, 0.80 g/kg) in 20 social drinkers. At doses that produced comparable psychomotor impairment, triazolam was more likely to impair several objective measures of cognitive performance (e.g., episodic memory, divided attention) and to slow performance across several measures. However, only alcohol impaired accuracy on the digit symbol substitution and semantic memory tasks. In addition to objective measures, both drugs impaired awareness of performance impairments (i.e., metacognition) such that participants overestimated impairment, and the magnitude of this effect was generally larger for alcohol. Only triazolam impaired other measures of metacognition (e.g., error detection on a choice reaction time task). Future research might examine the clinical implications of the performance impairments reported here given the widespread use of benzodiazepines and alcohol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunological and trophical effects of Saccharomyces boulardii on the small intestine in healthy human volunteers

Recently we investigated the mechanisms mediating the transport of valproic acid (VPA) between blood and brain. In one study efflux of valproic acid (VPA) from rabbit brain was inhibited by probenecid. Efflux of VPA decreased when probenecid was given intravenously but not when probenecid was given by ventriculocisternal (VC) perfusion indicating that the major site of probenecid-sensitive transport was at the brain capillary endothelium and not at the choroid plexus. In another study VPA transport into rat brain was inhibited by para-aminohippurate (PAH). The purpose of the present study were to determine (a) if the efflux of VPA from rabbit brain was also inhibited by PAH, and (b) whether efflux of VPA could occur at the choroid plexus via an PAH-selective transport system. Six control rabbits received VPA by intravenous infusion and tracer concentrations of [3H]VPA and [14C]PAH by VC perfusion. Rabbits in the PAH group (n = 6) received identical treatment with VPA, tracer concentrations of [3H]VPA and [14C]PAH and, in addition, received 20 mM PAH by VC perfusion. PAH had no effect on the VC extraction ratio of [3H]VPA or the steady-state brain concentration of intravenously administered VPA. It is concluded that the efflux of VPA at the rabbit blood-brain barrier is mediated by a transporter different from the PAH-like transporter responsible for the uptake of VPA into rat brain. In addition, the finding that VC perfusion with PAH had no effect on the VC extraction of [3H]VPA provides further evidence that the choroid plexus plays a negligible role in removal of VPA from the CNS.