Dose-response relationship of perineural dexamethasone for interscalene brachial plexus block: a randomised, controlled, triple-blind trial.

Perineural dexamethasone has a ceiling dose of 4 mg for prolongation of analgesia duration after injection of long-acting local anaesthetic for peripheral nerve block, but evidence for doses < 4 mg is lacking. This randomised controlled triple-blind trial tested the hypothesis that increasing doses of perineural dexamethasone between 1 mg and 4 mg would prolong the duration of analgesia in a dose-dependent manner. Eighty ASA physical status 1-2 patients scheduled for shoulder arthroscopy under general anaesthesia with ultrasound-guided interscalene brachial plexus block were randomly allocated to receive saline (control), dexamethasone 1 mg, 2 mg, 3 mg and 4 mg, together with 20 ml ropivacaine 0.5%. Postoperative analgesia consisted of paracetamol, diclofenac and oxycodone on request, using a pre-defined protocol. The primary outcome was the duration of analgesia, defined as the time between the block procedure and the first analgesic request. Secondary outcomes included rest and dynamic pain scores, and analgesic consumption at 2 h, 24 h and 48 h postoperatively. An analysis of the dose-response relationship was performed using multiple comparison procedure-modelling. The median (IQR [range]) duration of analgesia was significantly prolonged in a dose-dependent manner: control 685 (590-860 [453-1272]) min; 1 mg 835 (740-1110 [450-1375]) min; 2 mg 904 (710-1130 [525-1365]) min; 3 mg 965 (875-1025 [730-1390]) min; 4 mg 1023 (838-1239 [518-1500]) min (p = 0.03). There were no significant differences between the secondary outcomes. Perineural administration of dexamethasone with doses between 1 mg and 4 mg, combined with ropivacaine for interscalene brachial plexus block, prolongs duration of analgesia in a dose-dependent manner.

Colectomy Rates in Ulcerative Colitis are Low and Decreasing: 10-year Follow-up Data From the Swiss IBD Cohort Study.

OBJECTIVES: Previous population-based studies in patients with ulcerative colitis [UC] revealed variable colectomy rates and colectomy-associated risk factors. Over the past two decades, a decrease in colectomy rates was observed. We assessed risk factors and colectomy rates over time in UC in the Swiss Inflammatory Bowel Disease Cohort Study [SIBDCS]. METHODS: Prospectively collected SIBDCS data, including disease history, baseline characteristics at enrolment, and course of disease, were retrospectively analysed. Cumulative and adjusted annual colectomy rates were calculated. RESULTS: Among 1245 UC patients analysed [54.6% male], 114 [9.2%] underwent colectomy. We observed 5-, 10-, 15-, and 20-year cumulative colectomy rates after diagnosis of 4.1%, 6.4%, 10.4%, and 14.4% of patients, respectively. Male sex (odds ratio [OR] 1.54; p = 0.035), pancolitis at diagnosis [OR = 2.16; p = 0.005], younger age at diagnosis [OR 0.89 per 5 years of age; p = 0.006] and presence of extraintestinal manifestations [EIM] [OR 2.30; p < 0.001] were risk factors for undergoing colectomy. We did not observe a significant protective effect of smoking on colectomy risk [OR 0.64; p = 0.106]. The majority of colectomies were performed within first 10 years of disease onset, with a rapidly decreasing colectomy rate after 15 years. In patients diagnosed after 2003, colectomy was performed much earlier during and individual's disease course. Nevertheless, we found a significantly decreasing trend in yearly colectomy rates over time after 2005. CONCLUSIONS: Crude and adjusted colectomy rates in Swiss UC patients were lower than those reported previously in the literature, and decreased over time.

A randomised controlled trial of placebo, droperidol or ondansetron to prevent nausea and vomiting after tonsillectomy in children receiving dexamethasone.

We tested whether prophylactic droperidol and ondansetron, in combination with a moderate dose of dexamethasone, were equally effective in reducing nausea and vomiting after tonsillectomy in children and that both were superior to saline with dexamethasone. We randomly allocated 300 children to intravenous saline, droperidol 10 µg.kg-1 or ondansetron 150 µg.kg-1 , after induction of anaesthesia and the administration of intravenous dexamethasone 250 µg.kg-1 . The rates (95%CI) of nausea or vomiting within 24 postoperative hours were: 42/91 after saline, 46% (36%-57%); 43/87 after droperidol, 49% (39%-60%); reduced to 18/84 by ondansetron, 21% (13%-32%), p < 0.001. There were no differences in the rates of side-effects between groups. We conclude that ondansetron is more effective than saline in preventing nausea or vomiting after paediatric tonsillectomy when given with a moderate dose of dexamethasone, whereas droperidol was not.

Reduced hemidiaphragmatic paresis with extrafascial compared with conventional intrafascial tip placement for continuous interscalene brachial plexus block: a randomized, controlled, double-blind trial.

BACKGROUND.: The incidence of hemidiaphragmatic paresis with continuous interscalene brachial plexus block (CISB) can approach 100%. We tested the hypothesis that extrafascial placement of the catheter tip reduces the rate of hemidiaphragmatic paresis compared with intrafascial tip placement for CISB while providing effective analgesia. METHODS.: Seventy patients undergoing elective major shoulder surgery under general anaesthesia were randomized to receive an ultrasound-guided CISB plexus block for analgesia with the catheter tip placed either within (intrafascial group) or immediately outside (extrafascial group) the brachial plexus sheath midway between the levels of C5 and C6. Catheters were bolus dosed with ropivacaine 0.5% 20 ml before surgery, followed by an infusion of ropivacaine 0.2% at 4 ml h -1 for the first 2 days after surgery. The primary outcome was hemidiaphragmatic paresis measured by M-mode ultrasonography on postoperative day (POD) 1. Secondary outcomes included forced vital capacity, forced expiratory volume in 1 s, and rest pain scores. RESULTS.: The incidence of hemidiaphragmatic paresis on POD 1 was significantly reduced in the extrafascial group {intrafascial, 41% [95% confidence interval (CI) 25-59%]; extrafascial, 15% (95% CI 5-32%); P =0.01}. We were unable to detect a difference between groups in any of the functional respiratory outcomes or in rest pain scores [numerical rating scale (1-10): intrafascial, 3 (95% CI 2-3); extrafascial, 3 (95% CI: 2-4); P =0.93] on POD 1. CONCLUSIONS.: Placement of the catheter tip immediately outside of the brachial plexus sheath reduced the incidence of hemidiaphragmatic paresis on POD 1 associated with ultrasound-guided CISB while providing effective analgesia after major shoulder surgery. Our results do not support the routine placement of the catheter tip within the brachial plexus sheath for CISB. CLINICAL TRIAL REGISTRATION.: NCT02433561.

A systematic review of ultrasound-guided methods for brachial plexus blockade.

We systematically reviewed 25 randomised controlled trials of ultrasound-guided brachial plexus blockade that recruited 1948 participants: either one approach vs another (axillary, infraclavicular or supraclavicular); or one injection vs multiple injections. There were no differences in the rates of successful blockade with approach, relative risk (95% CI): axillary vs infraclavicular, 1.0 (1.0-1.1), p = 0.97; axillary vs supraclavicular, 1.0 (1.0-1.1), p = 0.68; and infraclavicular vs supraclavicular, 1.0 (1.0-1.1), p = 0.32. There was no difference in the rate of successful blockade with the number of injections, relative risk (95% CI) 1.0 (1.0-1.0), p = 0.69, for one vs multiple injections. The rate of procedural paraesthesia was less with one injection than multiple injections, relative risk (95% CI) 0.6 (0.4-0.9), p = 0.004.

Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn's disease.

BACKGROUND: The impact of early treatment with immunomodulators (IM) and/or TNF antagonists on bowel damage in Crohn's disease (CD) patients is unknown. AIM: To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. METHODS: Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. RESULTS: The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio (HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery (HR 0.322, P = 0.005), and perianal surgery (HR 0.361, P = 0.042), as well as developing any complication (HR 0.567, P = 0.006). CONCLUSIONS: Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

BACKGROUND: Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. AIM: To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. METHODS: Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. RESULTS: A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. CONCLUSIONS: Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent.

The gap between scientific evidence and clinical practice: 5-aminosalicylates are frequently used for the treatment of Crohn's disease.

BACKGROUND: There is uncertain evidence of effectiveness of 5-aminosalicylates (5-ASA) to induce and maintain response and remission of active Crohn's disease (CD), and weak evidence to support their use in post-operative CD. AIM: To assess the frequency and determinants of 5-ASA use in CD patients and to evaluate the physicians' perception of clinical response and side effects to 5-ASA. METHODS: Data from the Swiss Inflammatory Bowel Disease Cohort, which collects data since 2006 on a large sample of IBD patients, were analysed. Information from questionnaires regarding utilisation of treatments and perception of response to 5-ASA were evaluated. Logistic regression modelling was performed to identify factors associated with 5-ASA use. RESULTS: Of 1420 CD patients, 835 (59%) were ever treated with 5-ASA from diagnosis to latest follow-up. Disease duration >10 years and colonic location were both significantly associated with 5-ASA use. 5-ASA treatment was judged to be successful in 46% (378/825) of treatment episodes (physician global assessment). Side effects prompting stop of therapy were found in 12% (98/825) episodes in which 5-ASA had been stopped. CONCLUSIONS: 5-Aminosalicylates were frequently prescribed in patients with Crohn's disease in the Swiss IBD cohort. This observation stands in contrast to the scientific evidence demonstrating a very limited role of 5-ASA compounds in the treatment of Crohn's disease.

Amygdala kindling disrupts trace and delay fear conditioning with parallel changes in Fos protein expression throughout the limbic brain.

Amygdala kindling is well known to increase unconditioned fear and anxiety. However, relatively little is known about whether this form of kindling causes functional changes within the neural circuitry that mediates fear learning and the retrieval of fear memories. To address this issue, we examined the effect of short- (i.e., 30 stimulations) and long-term (i.e., 99 stimulations) amygdala kindling in rats on trace and delay fear conditioning, which are aversive learning tasks that rely predominantly on the hippocampus and amygdala, respectively. After memory retrieval, we analyzed the pattern of neural activity with Fos, the protein product of the immediate early gene c-fos. We found that kindling had no effect on acquisition of the trace fear conditioning task but it did selectively impair retrieval of this fear memory. In contrast, kindling disrupted both acquisition and retrieval of fear memory in the delay fear conditioning task. We also found that kindling-induced impairments in memory retrieval were accompanied by decreased Fos expression in several subregions of the hippocampus, parahippocampus, and amygdala. Interestingly, decreased freezing in the trace conditioning task was significantly correlated with dampened Fos expression in hippocampal and parahippocampal regions whereas decreased freezing in the delay conditioning task was significantly correlated with dampened Fos expression in hippocampal, parahippocampal, and amygdaloid circuits. Overall, these results suggest that amygdala kindling promotes functional changes in brain regions involved in specific types of fear learning and memory.

Topical therapy is underused in patients with ulcerative colitis.

The availability of new topical preparations for the treatment of left sided ulcerative colitis offers a therapy optimization for many patients. Rectal application of steroids and 5-aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in left-sided colitis as compared to a systemic therapy. Therefore, we were interested in the use of topical therapy in patients with ulcerative colitis. The key question was whether topical treatment is more frequently used than oral therapy in patients with proctitis and left sided colitis. Data of 800 patients of the Swiss IBD cohort study were analyzed. Sixteen percent of patients of the cohort had proctitis, 21% proctosigmoiditis and 41% pancolitis. Topical therapy with 5-ASA or corticosteroids was given in 26% of patients with proctitis, a combined systemic and topical treatment was given in 13%, whereas systemic treatment with 5-ASA without topical treatment was given in 29%. Proportion of topical drug use decreased with respect to disease extension from 39% for proctitis to 13.1% for pancolitis (P=0.001). Patients with severe colitis received a significantly higher dose of topical 5-ASA than patients in remission. Side effects of topical or systemic 5-ASA or budesonide treatment were less frequently seen compared to other medications. Topical treatment was frequently stopped over time. The quality of life was the same in patients with limited disease compared to patients with pancolitis. Topical treatment in proctitis patients was underused in Switzerland. Since topical treatment is safe and effective it should be used to a larger extend.

Measurement of the binding energies of the organic-metal perylene-teracarboxylic-dianhydride/Au111 bonds by molecular manipulation using an atomic force microscope.

Based on single molecule manipulation experiments in a combined scanning tunneling microscope/frequency modulated atomic force microscope, we quantify the individual binding energy contributions to an organic-metal bond experimentally. The method allows the determination of contributions from, e.g., local chemical bonds, metal-molecule hybridization, and van der Waals interactions, as well as the total adsorption energy.

The effect of amygdala kindling on hippocampal neurogenesis coincides with decreased reelin and DISC1 expression in the adult dentate gyrus.

Temporal lobe seizures can induce the proliferation and abnormal migration of newly generated dentate granule cells, but little is known about the molecular mechanisms that govern these pathological events. Reelin and DISC1 (disrupted-in-schizophrenia 1) are proteins that play a regulatory role in the maturation and integration of new neurons in the developing and adult brain. In this study, we examined whether amygdala kindling results in aberrant neurogenesis and altered expression of reelin and DISC1 in the adult dentate gyrus. Using doublecortin immunohistochemistry, we found that short-term kindling (i.e., 30 electrical stimulations) significantly increased the number of immature neurons in the dentate subgranular zone (SGZ), whereas long-term kindling (i.e., 99 electrical stimulations) did not. However, doublecortin-labeled neurons in long-term kindled rats showed greater dendritic complexity than they did in short-term kindled or control rats. We also found that long-term kindling decreased the number of reelin-positive cells and decreased DISC1 expression in the dentate granule cell layer and subgranular zone. Interestingly, kindling-induced changes in reelin and DISC1 expression coincided with the appearance of ectopically located Prox1-labeled granule cells in the hilus. These effects occurred independently of alterations in granule cell layer length, dentate volume, or the number of hilar neurons. Taken together, these findings suggest a novel role for DISC1 in the pathophysiology of temporal lobe epilepsy and further suggest that changes in reelin and DISC1 expression may contribute to aberrant neurogenesis in the kindling model.

[Trans fatty acids: effects on lipoprotein metabolism and cardiovascular risk]. / Acides gras trans : effets sur le métabolisme des lipoprotéines et le risque cardiovasculaire.

Dietary trans fatty acids (TFA) (mainly 18:1 isomers) have two sources: they are formed during the natural bacterial hydrogenation of unsaturated fatty acids in ruminants or they come from the industrial hydrogenation of unsaturated vegetable oils. Total trans fatty acids account for 1.3% of total energy intake in France compared to 2-3% in USA. Recent epidemiologic studies and meta-analyses of well-designed controlled trials clearly showed that trans fatty acids are associated with an increase of cardiovascular risk. It seems that TFA from industrial sources are responsible for the deleterious effects particularly on lipoprotein metabolism. Specifically the consumption of industrial TFA has been associated with high plasma concentrations of triacylglycerols, LDL-cholesterol and small dense LDL and lower HDL-cholesterol concentrations. The very recent interventional trials allowed for a comparison of TFAs from different sources suggest that the intake of natural TFA have no or neutral effects on plasma lipids and other cardiovascular risk factors. However, the mechanisms underlying the isomer-specific effects are not well understood and warrant further investigations.

Profound hypothermia determines the anticonvulsant and neuroprotective effects of swim stress.

In contrast to most stressors that appear to be proconvulsant in nature, forced swimming (or swim stress) produces substantial anticonvulsant effects. Here we describe a series of experiments designed to identify the specific factors of swim stress (e.g., duration, swimming behavior, water temperature, and frequency of exposure) that are essential for the emergence of anticonvulsant effects in the rat. Our results revealed that the anticonvulsant effect of swim stress against lithium-pilocarpine convulsions occurred only when swim durations were at least 5 min in length and in water temperatures of 20 degrees C or less. Moreover, this anticonvulsant effect was not associated with habituation even after 10 days of repeated swimming. Treatment with lithium-pilocarpine coupled with 10 degrees C or 20 degrees C swim stress for 10 min caused pronounced hypothermia (10 to 15 degrees C reduction in body temperature) that required at least 12 h to return to baseline. One day after seizures were induced, swim stressed rats showed significantly fewer degenerating neurons in the hippocampus as revealed by Fluoro-Jade B staining. These results suggest that dramatically lowered body temperature could be the critical factor that produces the anticonvulsive and neuroprotective effects of swim stress.

Impaired social cognition 30 years after hemispherectomy for intractable epilepsy: the importance of the right hemisphere in complex social functioning.

Clinical research with individuals following hemispherectomy typically quantifies the success of surgical outcomes by focusing primarily on the achievement of seizure control and the preservation of general brain functions, such as movement, sensation, language, and memory. In addition to these outcomes, careful study of individuals following hemispherectomy also has the potential to contribute to our understanding of functional brain asymmetries involving other complex cognitive behaviors. In this study, we report preliminary evidence for the lateralization of social perception. We administered a series of neuropsychological tests that were developed to assess emotional recognition and the formation of social inferences and advanced social cognitive judgments, as they occur in everyday situations, to two adult participants who underwent complete anatomic left- or right-sided hemispherectomy. Our results show that despite a 30-year postsurgical period of recovery and consistent and high levels of family support and social engagement, distinct cognitive profiles are still evident between our right- and left-sided participants. In particular, participant S.M., who underwent an anatomic right hemispherectomy, showed the most severe impairments in identifying negative emotional expressions and conversational exchanges involving lies and sarcasm and in "mentalizing" the intent of others. In contrast, participant J.H., who underwent an anatomic left hemispherectomy was highly skilled interpersonally, despite evident language-related limitations, and showed only mild difficulties when asked to identify emotional expressions involving disgust and anger. These results suggest that the right hemisphere plays a particularly important role in social cognitive functioning and reasoning. Further examination of the extent of social perceptual difficulties prior to and following surgical intervention for epilepsy may guide the development of effective social skills training programs that can improve quality of life beyond seizure control.

Effect of pulp reduction and pasteurization on the release of aroma compounds in industrial orange juice.

Release of aroma compounds in orange juice according to pulp content and pasteurization was performed by headspace-solid phase microextraction (HS-SPME), HS-SPME-GC-olfactometry, and by the determination of partition coefficients of aroma compounds between the juice and the headspace. Orange juices with 12% and 6% pulp contents were collected from a processing line before and after pasteurization. HS-SPME revealed that the 6% pulp juice was the most affected by pasteurization, with an increase in the release of several aroma compounds that are generated by heat treatment (that is, alpha- and beta-terpinéol) and a decrease in the release of compounds sensitive to pasteurization (that is, neral and geranial). Principal component analysis of olfactometric data allowed discriminating fresh and pasteurized juices, regardless of the pulp content. The determination of the gas/liquid partition coefficients by the phase ratio variation method was possible for 7 aroma compounds. For the most hydrophobic ones, the release of aroma compounds in fresh juices was higher in the 6% pulp juice than in the 12% pulp juice. However, in pasteurized juices, the difference between their partition coefficients was less marked. Potential interactions between cloud proteins and hydrophobic aroma compounds may explain this phenomenon.

Sorption of aroma compounds in PET and PVC during the storage of a strawberry syrup.

The sorption of 14 aroma compounds into PET and PVC was monitored during storage of a strawberry syrup for 1 year. Concentrations in the syrup and in the polymer were determined during storage and compared with previously published results obtained with glass bottles. Apparent partition coefficients between the polymer and the syrup (noted K app) were estimated from experimental kinetics without reaching equilibrium K app values and optimally identified from the kinetic data obtained between 30 and 90 days. They exhibited a similar behaviour for both polymers with values were between 2 x 10(-5) and 2 x 10(-3), 4 x 10(-5) and 3 x 10(-2), respectively, for PET and PVC. The variation of K app values in PET was mainly correlated to the polarity of tested compounds as assessed by their log P values. By contrast, the variations in K app values for PVC were mainly related to their chain lengths. Due to slightly higher partition coefficients and diffusion coefficients in PVC compared with PET, the amount of absorbed aroma was four times higher in PVC than in PET; however, the amount of absorbed aroma compounds was less than 0.1% of the initial amount present into the syrup, except for octyl butanoate. The variation in concentration in the syrup was interpreted as a combination of a degradation process and a transport process into the packaging material. Both effects were particularly noticeable for both PET and unstable aroma compounds.

Comparison of different cellular models measuring in vitro the whole human serum cholesterol efflux capacity.

BACKGROUND: Fu5AH rat hepatoma cells and cAMP (cyclic AMP)-pretreated J774 mouse macrophages are commonly used as models for SR-BI (scavenger receptor class B type I) and ABCA1 (ATP binding cassette transporter 1)-mediated free cholesterol efflux to whole serum, respectively. However, the responsiveness of Fu5AH, control or cAMP pretreated J774 cells to the various lipids and HDL (high-density lipoprotein)-parameters from both normo- and dyslipidaemic subjects has never been compared within the same study. MATERIALS AND METHODS: Fifty-eight men were classified into four groups: type IIa hypercholesterolaemic (n = 12), type IIb dyslipidaemic (n = 13), type IV hypertriglyceridaemic (n = 18) and normolipidaemic (n = 15) were recruited. A complete lipid profile including prebeta-HDL was performed. Cholesterol efflux from Fu5AH cells as well as from control or cAMP pretreated J774 cells were measured; the difference between these two latter values being taken as the ABCA1-mediated efflux. RESULTS: The Fu5AH and the control J774 cells delivered cholesterol to mature HDLs, especially to phospholipid (PL)-rich HDL. Using cAMP pretreated cells, the ABCA1-dependent efflux was highly sensitive to prebeta-HDL, which appeared to be a factor in determining the efflux. Consistent with the dependence of the SR-BI-mediated efflux on HDL-PL levels, which are not different between groups, all sera displayed similar efflux capacities from the Fu5AH cells. Conversely, in accordance with their high prebeta-HDL levels, the ABCA1-dependent efflux highlighted the efficiency of type IV sera. CONCLUSION: Two complementary cellular models providing SR-BI and ABCA1-dependent efflux should be used to measure the capacity of a biological fluid which contains a wide variety of components to promote cholesterol efflux.

Alpha2-adrenergic inhibition prevents the accompanied anticonvulsant effect of swim stress on behavioral convulsions induced by lithium and pilocarpine.

There has been much debate regarding the potential influence of stress on epilepsy. Many studies have reported that stress can affect seizure susceptibility through eliciting either proconvulsant or anticonvulsant effects within the nervous system. In this study, we investigated the potential anticonvulsant effect of a 10-min swim stress on convulsions induced by a single systemic injection of lithium chloride followed 4 h later with pilocarpine. Rats pretreated with lithium chloride and exposed to a 10-min swim stressor prior to pilocarpine injection displayed a significant delay to seizure onset compared to unstressed rats or rats exposed to swim stress 10 min after lithium chloride, 2 h after lithium chloride, or immediately after pilocarpine injection. We then determined whether administration of a glucocorticoid antagonist (mifepristone; 10 or 50 mg/kg), an alpha(2)-adrenergic antagonist (yohimbine; 2 or 5 mg/kg), or a nonspecific opioid blocker (naloxone; 0.2 or 1 mg/kg) could prevent the anticonvulsant effect of swim stress. Only the high dose of yohimbine was capable of inhibiting the anticonvulsant effect of swim stress on lithium-pilocarpine seizures. Our findings highlight the importance of an endogenous noradrenergic-dependent anticonvulsant system in mediating the effects of swim stress on seizures. Further studies exploring the benefits of treatments with noradrenergic acting drugs in epilepsy is well warranted.