Investigation of the anxiolytic effects of xanthohumol, a component of humulus lupulus (Hops), in the male Sprague-Dawley rat.

The purpose of this study was to investigate the anxiolytic effects of xanthohumol, a component of Humulus lupulus (hops), and its potential interaction with the benzodiazepine binding site on the y-aminobutyric acid (GABAA) receptor in the male Sprague-Dawley rat. This was a prospective, randomized, between-subjects experimental study. Fifty-five rats were assigned to 1 Sof 5 groups with 11 rats per group: control (vehicle), xanthohumol, midazolam, midazolam with xanthohumol, and flumazenil with xanthohumol. In this study the elevated plus maze measured the behavioral components of anxiety and motor movements. A 2-tailed multivariate analysis of variance and least significant difference post hoc test was used to determine if a significant difference existed. Our data suggest that xanthohumol does not produce anxiolysis by modulation of the GABAA receptor; however, there may be a possible interaction between xanthohumol and midazolam, or xanthohumol may influence the modulation of another neurotransmitter site in the central nervous system. Alone, xanthohumol does not show significant modulation of the benzodiazepine receptor. Additional research should investigate if xanthohumol acts as a benzodiazepine GABAA partial agonist or antagonist or if it modulates another neurotransmitter system in the central nervous system.

Comparison of tibial intraosseous, sternal intraosseous, and intravenous routes of administration on pharmacokinetics of epinephrine during cardiac arrest: a pilot study.

The purpose of this study was to determine and compare the maximum concentration (C(max)) and time to maximum concentration (T(max)) of epinephrine administered via tibial intraosseous (IO), sternal IO, and intravenous (i.v.) routes in a porcine model of cardiac arrest during cardiopulmonary resuscitation. Five pigs each were randomly assigned to 3 groups: tibial IO, sternal IO, and i.v. Cardiac arrest was induced with i.v. potassium chloride. After 2 minutes, cardiopulmonary resuscitation was initiated. Epinephrine was administered to each animal, and serial blood samples were collected over the next 3 minutes. Enzyme-linked immunosorbent assay was used to determine the epinephrine concentration. Multivariate analysis of variance helped determine if there were statistically significant differences between groups. There were significant differences in Cmax between the sternal IO and i.v. (P = .009) and tibial IO and i.v. (P = .03) groups but no significant difference between tibial and sternal IO groups (P = .75). Significant differences existed in Tmax between the tibial IO and i.v. (P = .04) and between tibial IO and sternal IO (P = .02) groups but no difference between the sternal IO and i.v. groups (P = .56). Intravenous administration of 1 mg of epinephrine resulted in a serum concentration 5.87 and 2.86 times greater than for the tibial and sternal routes, respectively.

Investigation of the anxiolytic effects of naringenin, a component of Mentha aquatica, in the male Sprague-Dawley rat.

This was a prospective, randomized, between-subjects experimental study to investigate the anxiolytic effects of naringenin, a component of mentha aquatica, and its potential interaction with the benzodiazepine binding site on the γ-aminobutyric acid (GABAA) receptor in the rat. Fifty-five rats were assigned to one of 5 groups with 11 rats per group: control, naringenin, midazolam, midazolam with naringenin, and flumazenil with naringenin. The elevated plus maze measured the behavioral components of anxiety and motor movements. Our data suggest that naringenin does not produce anxiolysis by modulation of the GABAA receptor; however, the findings indicate that naringenin decreases motor movements (P < .05).

Evaluation of the anxiolytic properties of myristicin, a component of nutmeg, in the male Sprague-Dawley rat.

The purpose of this study was to investigate the anxiolytic effects of myristicin, a major compound found in nutmeg, and its potential interaction with the gamma-aminobutyric acid (GABA(A)) receptor in male Sprague-Dawley rats. Nutmeg has traditionally been used as a spice in food preparation and as an herbal remedy in the treatment of many medical conditions, including anxiety. Fifty-five rats were divided equally into 5 groups: control (vehicle); myristicin; midazolam (positive control); flumazenil and myristicin; and midazolam and myristicin. The behavioral component of anxiety was examined by using the elevated plus-maze (open-arm and closed-arm times) along with analysis of gross and fine motor movements. Data analysis was performed using a 2-tailed multivariate analysis of variance (MANOVA) and least significant difference post-hoc test. Our data suggest that myristicin does not decrease anxiety by modulation of the GABA(A) receptor but may promote anxiogenesis. When myristicin was combined with midazolam, an antagonist-like effect similar to the flumazenil and myristicin combination was exhibited by a decrease in anxiolysis compared with the midazolam-only group. Myristicin may antagonize the anxiolytic effects of midazolam, increase anxiety, and affect motor movements.

Evaluation of the anxiolytic properties of tetrahydropalmatine, a Corydalis yanhusuo compound, in the male Sprague-Dawley rat.

The purpose of this study was to investigate the anxiolytic effects of tetrahydropalmatine (THP) and its potential interaction with the benzodiazepine binding site on the gamma-aminobutyric acid (GABAA) receptor in the male Sprague-Dawley rat. Tetrahydropalmatine (THP), an active component isolated from the Chinese herbal plant Corydalis yanhusuo, is used in Asia for its analgesic, sedative, and hypnotic properties during herbal therapy. Fifty-five rats were assigned to 1 of 5 groups with 11 rats per group: 1) control (vehicle), 2) THP, 3) midazolam, 4) midazolam with THP, and 5) flumazenil with THP. In this study, the elevated plus-maze measured the behavioral components of anxiety and motor movements. The data were analyzed using a 2-tailed multivariate analysis of variance to determine if a significant difference existed followed by the least significant difference post hoc test. The findings suggest that THP, 25 mg/kg, given via intraperitoneal injection, results in significant anxiolysis and decreased motor movements. Furthermore, flumazenil, 3 mg/kg, does not fully antagonize the effects of THP.

Investigation of the anxiolytic effects of luteolin, a lemon balm flavonoid in the male Sprague-Dawley rat.

The purpose of this study was to investigate the anxiolytic effects of luteolin and its potential interaction with the gamma-aminobutyric acid (GABAA) receptor in male Sprague-Dawley rats. Lemon balm has traditionally been used as an herbal remedy in the treatment of many medical conditions, including anxiety. Luteolin is a major component of the essential oil lemon balm. We divided 55 rats into 5 groups: (1) control (negative control), (2) luteolin, (3) midazolam (positive control), (4) flumazenil and luteolin, and (5) midazolam and luteolin. The behavioral component of anxiety was examined by using the elevated plus-maze (open arm time/total time) and motor movements. Data analyses were performed using a 2-tailed multivariate analysis of variance and Sheffé post hoc test. Our data suggest that luteolin does not produce anxiolysis by modulation of the GABAA receptor; however, luteolin may modulate motor movements and locomotion.

Anxiolytic effects of L-theanine--a component of green tea--when combined with midazolam, in the male Sprague-Dawley rat.

The purpose of the study was to investigate the anxiolytic effects of L-theanine and its potential interaction with the GABAA receptor in Sprague-Dawley rats. L-theanine is a major component of green tea, which has traditionally been used as an herbal remedy in the treatment of many medical conditions, including anxiety. Herbals and supplements and their potential interactions perioperatively are a concern to anesthetists. Fifty-five rats were divided into 5 groups: control (saline); L-theanine (positive control); flumazenil (a known benzodiazepine receptor antagonist) and L-theanine; and midazolam and L-theanine. The behavioral component of anxiety was evaluated using the elevated plus-maze and calculated by the time spent in the open arm of the maze divided by total time in the maze. Data were analyzed using a 2-tailed multivariate analysis of variance and Sheffé posthoc test. The data suggest that L-theanine does not produce anxiolysis by modulation of the GABAA receptor; however, in combination with midazolam, a synergistic or additive effect was demonstrated by decreased anxiety and both fine and basic motor movements. These data may provide direction for further studies examining L-theanine and its effects on anxiety and motor activity.

Investigation of the anxiolytic effects of linalool, a lavender extract, in the male Sprague-Dawley rat.

The purpose of our study was to investigate the anxiolytic effects of linalool and its potential interaction with the GABAA receptor in Sprague-Dawley rats. Lavender has been used traditionally as an herbal remedy in the treatment of many medical conditions, including anxiety. Linalool is a major component of the essential oil of lavender. Forty-four rats were divided into 4 groups: control, linalool, midazolam (positive control), and flumazenil and linalool. The behavioral and the neurohormonal/physiological components of anxiety were evaluated. The behavioral component was examined by using the elevated plus maze (open arm time/total time) and the neurohormonal/physiological component by measuring serum catecholamine and corticosterone levels. Data analysis was performed using a 2-tailed Multivariate Analysis of Variance and Sheffe post-hoc test. Our data suggest that linalool does not produce anxiolysis by modulation of the GABAA receptor; however, linalool may modulate motor movements and locomotion.

Evaluation of the anxiolytic effects of chrysin, a Passiflora incarnata extract, in the laboratory rat.

The definitive anxiolytic effects of Passiflora incarnata are unknown. We studied the potential anxiolytic effects of chrysin, a Passiflora extract, and the purported modulation of the benzodiazepine receptor on the GABA(A) receptor in laboratory rats. We hypothesized that chrysin decreases anxiety via interaction with the GABA(A) receptor in laboratory rats as measured by elevated plus-maze (EPM), corticosterone, and catecholamine assays. We randomized 44 male Sprague-Dawley rats in a double-blind, placebo-controlled, between-subjects experimental design. Each animal received an intraperitoneal injection of (1) vehicle (DMSO 4%), (2) chrysin, 2 mg/kg, (3) midazolam, 1.5 mg/kg, or (4) flumazenil, 3 mg/kg and chrysin, 2 mg/kg. The EPM was used to evaluate the behavioral component of anxiolysis, and catecholamine and corticosterone assays were examined to measure the neurohormonal effects of anxiety. No statistical difference was found among groups in catecholamine and corticosterone levels. Midazolam significantly decreased anxiety compared with control and flumazenil plus chrysin groups (P <.05); there was no significant difference compared with the chrysin group. These data suggest that chrysin may have anxiolytic properties similar to midazolam but to a lesser magnitude at the 2 mg/kg dose used in this study.

Cullin-5 is ubiquitous in the rat brain.

Cullin-5 (Cul-5), an E3 ubiquitin ligase that covalently binds ubiquitin to proteins targeted for degradation via the proteasome, was examined for its localization and distribution in the rat central nervous system (CNS). We showed cul-5 mRNA expression in rat neuronal, glial, and vascular endothelial cells by reverse transcription-polymerase chain reaction and corroborated these data by Cul-5 immunostaining in neurons, astrocytes, blood vessels, and choroid plexus of the laboratory rat. Widespread and ubiquitous expression of Cul-5 in the brain suggests that it may have a vital role(s) in cellular activities of the CNS.

Alterations of cullin-5 mRNA levels in the rat central nervous system following hemorrhagic shock.

Hemorrhagic shock is a clinical syndrome that manifests as hypoperfusion, hypoxia, and ischemia initiating various cellular stress responses involved in the synthesis and release of an assortment of pro-inflammatory molecules, cytokines, chemokines, and reactive oxidant species (ROS). The ROS have been shown to oxidize and damage proteins making them targets for ubiquitination and proteasomal degradation. Cullin-5 (cul-5), an E3 ligase that binds ubiquitin to proteins targeted for degradation via the proteasome, was investigated for its gene expression during hemorrhagic shock. Male Long-Evans rats were subjected to volume controlled (27 ml kg-1) hemorrhage over 10 min and kept in shock for 60 min. Quantitative realtime polymerase chain reaction showed cul-5 mRNA levels were significantly increased in the brainstem and cerebellum, and decreased in the hypothalamus of rats as a result of hemorrhagic shock (n = 6) compared to sham-treated rats (n = 6). Cul-5 mRNA levels in the cerebral cortex, small intestine, kidney, liver, lung, or pituitary gland did not significantly change after hemorrhagic shock. This is the first report of cul-5 mRNA regulation by hemorrhagic shock. Evidence indicates this protein may have a regulatory role in ubiquitin-proteasomal protein degradation in response to hemorrhagic shock.

Osmotic stress increases cullin-5 (cul-5) mRNA in the rat cerebral cortex, hypothalamus and kidney.

Cullin-5 (cul-5), a member of the cullin gene family, may have a role in proteolysis and cell cycle regulation. Our recent study demonstrated that cul-5 mRNA is ubiquitously expressed in the central nervous system and many peripheral organs. The present study used quantitative realtime polymerase chain reaction to measure changes in cul-5 mRNA expression as a consequence of osmotic stress in vivo. Cul-5 mRNA levels were significantly increased in the rat cerebral cortex, hypothalamus and kidney following 48 h of water deprivation. Water deprivation for a shorter time period (24 h) or rehydration (24 h access to water following 48 h of water deprivation) also elevated kidney cul-5 mRNA levels. Water deprivation did not significantly alter cul-5 mRNA levels in the brainstem, cerebellum, hippocampus, lung or liver. Since cul-5 appears to be linked to proteosome-mediated protein degradation, it may have a role in protein regulation under conditions of osmotic stress.

Etiology, mechanisms, and anesthesia implications of autoimmune myasthenia gravis.

Myasthenia gravis (MG) is the prototypical neurological autoimmune disease. It is characterized by muscle weakness that progressively worsens on repetition but improves with rest. Muscle weakness and fatigability arise from defective or decreased acetylcholine receptors at the neuromuscular junctions, where nerve signals from spinal motor neurons that innervate muscles cannot effectively induce muscle contraction. Several mechanisms of pathogenesis lead to the MG syndrome. The most prevalent cause of MG is an autoimmune disorder in which the patient produces antibodies that attack the nicotinic acetylcholine receptor at the neuromuscular junction. Anesthesia management of the patient with MG is challenging and requires specific management; however, safe and successful outcomes are achievable. This course emphasizes the autoimmune neuromuscular defect in MG, current treatments for this syndrome, contraindications of certain anesthetic drugs in this condition, and anesthetic management of a patient with MG in the operating room environment.