-
[show abstract]
[hide abstract]
ABSTRACT: We have developed a new detection method of blood remifentanil concentration using a gas chromatography-mass spectrometry(GC-MS) with fentanyl as the internal standard(IS). The detection was performed at m/z 168 and 245 for remifentanil and fentanyl, respectively. In addition, the retention times of remifentanil and fentanyl were 5 min 45 s and 6 min 51 s, respectively. The standard curve of relationship between remifentanil concentration and the ratio of the peak area of remifentanil to fentanyl was satisfactorily fitted as linear regression (R (2) = 0.998, p < 0.01). Intra- and inter-assay CV was 10.5 and 11.5 %, respectively. In the clinical setting, 21 adult patients undergoing elective surgery under propofol-remifentanil TIVA were enrolled. To determine blood remifentanil concentrations, arterial blood was obtained at 0-30 min after cessation of remifentanil infusion at 0.2 μg/kg/min. Blood samples were given into sample tubes(chilled on ice) containing citric acid 50 % 60 μl which inactivates all esterase, and then stored at -20 °C until assay. Measured blood remifentanil concentration was 3.59 ± 0.74 ng/ml at the end of remifentanil infusion, and the ime for a decrease in blood remifentanil concentration by half was ~2 min. Remifentanil concentration was below the detection limit 30 min after the cessation. Thus, we have confirmed that this new method is clinically applicable.
Journal of Anesthesia 01/2013; · 0.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A rectus sheath block can provide postoperative analgesia for midline incisions. However, information regarding the pharmacokinetics of local anesthetics used in this block is lacking. In this study, we detail the time course of ropivacaine concentrations after this block. Thirty-nine patients undergoing elective lower abdominal surgery were assigned to 3 groups receiving rectus sheath block with 20 mL of different concentrations of ropivacaine. Peak plasma concentrations were dose dependent, and there were no significant differences in the times to peak plasma concentrations. The present data also suggested a slower absorption kinetics profile for ropivacaine after rectus sheath block than other compartment blocks.
Anesthesia and analgesia 01/2012; 114(1):230-2. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neurotropin is a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, and used for treatment of neuropathic pain. In the present study, we have determined whether neurotropin could exert antinociceptive action using the central neuropathic pain model that we recently established. Rats were randomly allocated to 3 groups: Sham group (n=20), DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine] group (50mg/kg ip, n=18), and DSP-4+5,7-DHT [5,7-dihydroxytryptamine] group (ip DSP-4 50mg/kg+icv 5,7-DHT 200μg, n=18). In Sham, DSP-4 and DSP-4+5,7-DHT groups, the effects of ip neurotropin (100NU/Kg) on hot-plate latency in rats with no lesion, noradrenergic neuron depletion and both noradrenergic and serotonergic neuronal depletion were studied, respectively. Rats in each group were subdivided equally to 2 subgroups: saline and neurotropin. After completion of the hot-plate tests, each rat was decapitated, the cerebral cortex was dissected from its internal structure for measurement of norepinephrine contents. Hot-plate latency significantly decreased by ∼40% 10 days after ip DSP-4 or after ip DSP-4 and 5,7-DHT. Norepinephrine contents in DSP-4 treated rats (55.6±6.3ng/ng tissue) and DSP-4+5,7-DHT treated rats (35.3±6.3ng/ng tissue) were significantly lower than those in intact rats (131.6±5.7ng/ng tissue, p<0.01). Neurotropin significantly increased the area under the curve (AUC) of the hot-plate latency in the DSP-4 and DSP-4+5,7-DHT groups but not in the Sham group. There was a significant correlation between AUC and norepinephrine contents in saline subgroup (p<0.01, r=0.597) but not in neurotropin subgroup in DSP-4 group. Neurotropin exerted an antinociceptive effect in DSP-4 induced central neuropathic pain. The present data suggest neuronal pathways other than descending inhibitory noradrenergic and serotonergic systems may be involved in neurotropin mediated antinociception.
Neuroscience Letters 08/2011; 503(1):20-2. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Major physiological stress occurs during cardiac surgery with cardiopulmonary bypass. This is related to hypothermia and artificial organ perfusion. Thus, serious gastrointestinal complications, particularly upper gastrointestinal bleeding, sometimes follow cardiac surgery. We have compared the antisecretory effects of a preanesthetic H(2) antagonist (roxatidine, cardiopulmonary bypass-H(2) group, n = 15) and a proton pump inhibitor (rabeprazole, cardiopulmonary bypass-PPI group, n = 15) in patients undergoing cardiac surgery with cardiopulmonary bypass, and also compared in patients undergoing a off-pump coronary artery bypass graft surgery (off-pump cardiopulmonary bypass-H(2) group, n = 15). Gastric pH (5.14 ± 0.61) and gastric fluid volume (13.2 ± 2.4 mL) at the end of surgery in off-pump cardiopulmonary bypass-H(2) groups was significantly lower and higher than those in both cardiopulmonary bypass-H(2) (6.25 ± 0.54, 51.3 ± 8.0 mL) and cardiopulmonary bypass-PPI (7.29 ± 0.13, 63.5 ± 14.8 mL) groups, respectively although those variables did not differ between groups after the induction of anesthesia. Plasma gastrin (142 ± 7 pg/mL) at the end of surgery and maximal blood lactate levels (1.50 ± 0.61 mM) in off-pump cardiopulmonary bypass-H(2) group were also significantly lower than those in both cardiopulmonary bypass-H(2) (455 ± 96 pg/mL, 3.97 ± 0.80 mM) and cardiopulmonary bypass-PPI (525 ± 27 pg/mL, 3.15 ± 0.44 mM) groups, respectively. In addition, there was a significant correlation between gastric fluid volume and maximal blood lactate (r = 0.596). In conclusion, cardiopulmonary bypass may cause an increase in gastric fluid volume which neither H(2) antagonist nor PPI suppresses. A significant correlation between gastric fluid volume and maximal blood lactate suggests that gastric fluid volume may predict degree of gastrointestinal tract hypoperfusion.
Journal of Clinical Biochemistry and Nutrition 07/2011; 49(1):16-9. · 1.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neuropeptide S (NPS) and its receptor (NPSR) is a novel neuropeptide system that regulates arousal and anxiety. A link between natural sleep and general anesthesia has been suggested. Therefore, we hypothesized that the NPS neuronal system may also modulate general anesthesia.
The effects of intracerebroventricular NPS and [D-Cys(tBu)(5)]NPS, a peptide NPSR antagonist, on ketamine and thiopental anesthesia time were measured in rats. Anesthesia time was defined as the interval between the loss of righting reflex and its recovery.
Intracerebroventricular NPS 1 to 30 nmol significantly reduced ketamine anesthesia time, showing a bell-shaped dose-response curve. [D-Cys(tBu)(5)]NPS 20 nmol antagonized NPS 1 nmol effects and was per se able to increase ketamine anesthesia time. Similar results were obtained investigating thiopental anesthesia time that was significantly reduced by NPS and prolonged by [D-Cys(tBu)(5)]NPS.
NPS via selective NPSR activation stimulates the wakefulness-promoting pathway, thus reducing anesthesia duration. The endogenous NPS/NPSR system seems to tonically control these pathways.
Anesthesia and analgesia 02/2011; 112(4):845-9. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Massage therapy promotes psychosocial relaxation, reduces stress and has been reported to improve the immune function. As such, massage therapy is currently used in palliative care for the relief of anxiety and pain. Although psychosocial status has been evaluated using subjective psychological tests, such as State-Trait Anxiety Inventory (STAI), subjective psychological tests are of limited value if the subjects fail to report reliably. Salivary biomarkers have been recently suggested as useful objective markers for assessing psychosocial status. To determine whether salivary biomarkers are useful objective indices for assessing the effects of back massage on the mental status of 25 young healthy female volunteers, we measured heart rate and salivary biomarkers (α-amylase activity, cortisol, and chromogranin A) and assessed the STAI score before and after the back massage. Back massage significantly reduced the heart rate and STAI; however, salivary amylase and cortisol levels did not change. In contrast, the level of salivary chromogranin A significantly increased. We therefore conclude that changes in the salivary biomarkers tested here may not indicate changes in psychological status following massage therapy. However, the increase in chromogranin A release may contribute to the immunologically beneficial effects of massage therapy as chromogranin A has antibacterial and antifungal activity.
Journal of Anesthesia 12/2010; 24(6):955-8. · 0.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Central orexinergic and noradrenergic neurons are involved in the control of sleep and wakefulness. In addition, previous reports suggest that both neurons may have an important role to play in general anesthesia. In the present study, we have determined whether general anesthesia would affect plasma orexin A (OXA) and norepinephrine concentrations. Twelve patients scheduled for elective ophthalmic surgery under general anesthesia with sevoflurane, fentanyl and vecuronium were studied. Arterial blood was collected before and 1 and 2h after induction of anesthesia and at emergence to measure plasma OXA, cortisol, norepinephrine and epinephrine concentrations. During anesthesia the inhalational concentration of sevoflurane was changed to maintain the bispectral index between 40 and 50. Plasma OXA, cortisol, norepinephrine and epinephrine did not change during anesthesia but significantly increased after emergence compared to pre-anesthesia (from 14.8+/-1.7 to 21.4+/-1.7 pM, p<0.01, from 26.5+/-5.2 to 52.8+/-6.0 pM, p<0.01, from 263+/-46 to 513+/-89 pM, p<0.01, and from 1239+/-120 to 1631+/-203 pM, p<0.01, respectively). There were significant correlations of plasma OXA with cortisol (r=0.334, p<0.05) and epinephrine (r=0.292, p<0.05) but not with norepinephrine. In conclusion we found that plasma OXA significantly increased at emergence from sevoflurane-fentanyl anesthesia and this was probably via activation of the hypothalamic-pituitary-adrenal axis.
Neuroscience Letters 10/2010; 482(3):212-5. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with cancer suffer a wide range of physical symptoms coupled with psychological stress. Moreover, cancer chemotherapy induces immunosuppression and consequently causes respiratory infections. Massage therapy has been reported to reduce symptoms in cancer patients via an increase in psychosocial relaxation and to enhance and/or improve immune function.
In the present study, we determined whether leg massage could induce psychosocial relaxation and activate the first line of the host defense system. To assess effects of rest and leg massage, 15 healthy volunteers rested on a bed for 20 min on the first day, and 3 days later the subjects received a standardized massage of the legs for 20 min with nonaromatic oil. Twenty-nine cancer patients also received the same standardized massage of the legs. Anxiety/stress was assessed before and just after the rest or the massage using the State-Trait Anxiety Inventory (STAI-s) and visual analogue scale (VAS). To evaluate oral immune function, salivary chromogranin A (CgA) and secretory immunoglobulin A (sIgA) levels were measured.
In healthy volunteers, rest significantly reduced VAS by 34% and increased sIgA by 61%. In contrast, leg massage significantly reduced both STAI-s and VAS by 24% and 63%, and increased both sIgA and CgA by 104% and 90%, respectively. In cancer patients, leg massage significantly decreased both STAI-s and VAS by 16% and 38%, and increased both salivary CgA and sIgA by 33% and 35%, respectively.
Leg massage may promote psychosocial relaxation and reinforce a first-line host defense with an increase in secretion of antimicrobial peptides.
Journal of Anesthesia 10/2010; 24(6):827-31. · 0.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neuropathic pain models are classified as central and peripheral pain models. Although various peripheral neuropathic pain models are established, central pain models are based only on spinal cord injury. DSP-4 is a competitive inhibitor of norepinephrine uptake that selectively degenerates the locus coeruleus (LC)-noradrenergic neurons projection to the cerebral cortex and hippocampus. In the present study, we have tested whether lesion of LC-noradrenergic neurons by ip DSP-4 (0, 10, 30, 50 mg/kg, n=7 each) could provide a new central neuropathic pain model in rats using a hot-plate and tail-flick tests. DSP-4 significantly reduced the hot-plate latency and norepinephrine contents especially in the coerulean regions. However, DSP-4 did not change tail-flick latency. There are significant correlations of the latency in the hot-plate test with norepinephrine contents in the cerebral cortex (r=0.432, p=0.022), the hippocampus (r=0.465, p=0.013) and the pons (r=0.400, p=0.035) but not with those in the hypothalamus and the spinal cord. As response to hot-plate and tail-flick implies supra-spinal process and spinal reflex, respectively, central neuropathic pain may be facilitated by DSP-4 depleting LC-noradrenergic neurons although the present data are preliminary.
Neuroscience Letters 09/2010; 481(2):102-4. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Noradrenaline in the central nervous system plays an important role in regulating physiological functions, and is a key mechanistic component of general anesthesia. The purpose of this present study was to determine if nitrous oxide and xenon modulate noradrenaline release in the cerebral cortex. We performed a series of in vivo and in vitro experiments in rats. For the in vivo experiments, noradrenaline release was measured by microdialysis in the prefrontal cortex with exposure to 0, 30 or 60% nitrous oxide. For the in vitro experiments, noradrenaline release was measured from cerebrocortical slices before and after incubation with 0, 15, 30, or 60% nitrous oxide in Ca(2+)-containing buffer, Ca(2+)-free buffer, or in Ca(2+)-containing buffer with 10(-6)M tetrodotoxin (TTX). For the in vivo and in vitro experiments 60% xenon was also used. In the in vivo experiment, following exposure to nitrous oxide, noradrenaline release concentration-dependently increased. In the in vitro experiment, under Ca(2+)-containing conditions, noradrenaline release from cerebrocortical slices increased significantly during exposure to nitrous oxide in a concentration-dependent manner. Under Ca(2+)-free conditions, 60% nitrous oxide produced a significant release of noradrenaline. There were no significant differences in nitrous oxide-increased noradrenaline release between with and without TTX. Xenon also significantly increased noradrenaline release in the prefrontal cortex and from the cerebrocortical slices. The nitrous oxide-induced increase in noradrenaline release may be due to both excitation of the locus coeruleus-noradrenergic neuron and direct stimulation of its axon terminals.
Neuroscience Letters 12/2009; 469(2):199-203. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Urotensin II (UII) and its receptor (UT) are implicated in mood disorders, such as stress and anxiety, and this may result, at least in part, from increased norepinephrine release from the cerebral cortex. Benzodiazepines have been widely used as hypnotics and anxiolytics, producing a decrease in cerebrocortical norepinephrine release. We hypothesized that there was some interaction between benzodiazepines and the UII system in the cerebral cortex.
In the present study, we have examined the effects of benzodiazepines on UII-increased norepinephrine release from rat cerebrocortical slices and intracellular Ca(2+) concentrations ([Ca(2+)]i) in HEK293 cells expressing rat UT receptor (HEK293-rUT cells).
Midazolam, diazepam and flunitrazepam concentration-dependently inhibited UII-evoked norepinephrine release but did not affect [Ca(2+)]i. The IC(50) of midazolam for inhibition of UII-evoked norepinephrine release (0.32 microM, P < 0.01) was significantly lower than that of diazepam (187 microM) or flunitrazepam (40 microM). The inhibitory effects of midazolam on UII-evoked norepinephrine release were significantly attenuated by flumazenil, a benzodiazepine site antagonist.
The present study suggests that midazolam, at clinically relevant concentration, significantly inhibited UII-evoked norepinephrine release. This inhibitory effect may be partially mediated via central benzodiazepine receptors.
Anesthesia and analgesia 04/2009; 108(4):1177-81. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The H(2) receptor antagonist roxatidine is routinely used as an oral pre-anesthetic medication in surgical patients at night and 2 h before surgery. In the present study, we have compared the effects of roxatidine, rabeprazole and lansoprazole given singly at night as an alternative to the standard double roxatidine medication.
120 adult patients undergoing urological surgery were randomly assigned to three groups: roxatidine, rabeprazole and lansoprazole (n = 40 each). Following induction of anesthesia, gastric fluid was obtained by aspiration using a syringe to measure pH and volume of gastric contents.
Gastric volume (14.1 +/- 1.9 mL) in the lansoprazole group was significantly larger than that in roxatidine (8.6 +/- 1.7 mL) and rabeprazole (7.5 +/- 1.1 mL) groups (P < 0.05). Gastric pH in lansoprazole group (4.10 +/- 0.38) was also significantly lower than that in the roxatidine group (5.41 +/- 0.31, P < 0.05). The numbers of patients with critical factors for acid aspiration pneumonia (gastric pH < 2.5 or volume > 25 mL) in the lansoprazole group was significantly higher than in the roxatidine group (P < 0.05). Gastric pH and volume in all groups were constant even in the afternoon.
Single rabeprazole (but not lansoperazole) medication may be a suitable alternative to standard roxatidine for prophylaxis of acid aspiration pneumonia.
Journal of Gastroenterology and Hepatology 04/2009; 24(7):1244-7. · 2.87 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Orexins (OXs) regulate wakefulness, and a lack of OX Type-I receptors cause narcolepsy. OX selectively increases norepinephrine (NE) release from rat cerebral cortical slices, and brain noradrenergic neurons are involved in the sleep-wakefulness cycle. Ketamine increases NE release from the rat cerebral cortex. We hypothesized that OX would affect ketamine anesthesia's interactions with brain noradrenergic neuronal activity.
We used Sprague Dawley rats. We studied 1) in vivo effects of orexin A (OXA) and SB-334867-A (Orexin-1 receptor antagonist) on ketamine-induced anesthesia time, 2) in vivo effects of OXA on ketamine-induced increase in NE release from the frontal cortex assessed using microdialysis, and 3) in vitro effects of ketamine on OXA-evoked NE release from rat cerebrocortical slices.
1) Intracerebroventricular OXA 1 nmol significantly decreased ketamine anesthesia time by 20%-30% at 50, 100, and 125 mg/kg intraperitoneal (IP) ketamine. SB-334867-A fully reversed the decrease produced by OXA. 2) OXA also decreased the release of NE induced by ketamine even though OXA increased the release of NE in rat prefrontal cortex. Maximum NE release in Group OX + K (intracerebroventricular OXA 1 nmol + IP ketamine 100 mg/kg) was 271% and was significantly smaller than that in Group K (ketamine 100 mg/kg IP, 390% of baseline, P = 0.029). 3) Ketamine inhibited OX-evoked NE release with clinically relevant IC(50) values.
Orexinergic neurons may be an important target for ketamine. OXA antagonized ketamine anesthesia via Orexin-1 receptor with noradrenergic neurons.
Anesthesia and analgesia 03/2009; 108(2):491-5. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Orexin A and B, recently identified in the rat hypothalamus are endogenous neuropeptide agonists for the G-protein coupled orexin-1 (OX1) and orexin-2 (OX2) receptors.In the present study, we have examined the effects of orexin A, B and raised extracellular K+ on noradrenaline release from the rat cerebrocortical slice. We have compared this with other sleep – wake-related (excitatory) neurotransmitters; dopamine, glutamate, serotonin and histamine.Neurotransmitter release studies were performed in rat cerebrocortical slices incubated in modified Krebs buffer (with and without Ca2++EGTA 1 mM) with various concentrations of orexin A, B and K+ for various times.Orexin A and B-evoked (10−7 M) noradrenaline release was time-dependent reaching a maximum some 10 min after stimulation. K+ (40 mM) evoked release was also time dependent but reached a maximum after 6 min. Orexin A, B and K+ stimulation of release was concentration dependent with pEC50 and Emax (% of basal) values of 8.74±0.32 (1.8 nM) and 263±14% and 8.61±0.38 (2.4 nM) and 173±7% and 1.43±0.02 (37 mM) and 1430±70%, respectively. Orexin-evoked release was partially extracellular Ca2+ dependent.Of the other transmitters studied there was a weak orexin A and B stimulation of glutamate release. In contrast K+ evoked dopamine, glutamate, histamine and serotonin release with pEC50 and Emax (% of basal) values of 1.47±0.05 (34 mM) and 3430±410%, 1.38±0.04 (42 mM) and 1240±50%, 1.47±0.02 (34 mM) and 480±10% and 1.40±0.05 (40 mM) and 560±60% respectively.We conclude that the neuropeptides orexin A and B evoke noradrenaline release from rat cerebrocortical slices.British Journal of Pharmacology (2001) 134, 1461–1466; doi:10.1038/sj.bjp.0704409
British Journal of Pharmacology 01/2009; 134(7):1461 - 1466. · 4.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Several studies suggest that NMDA glutamate receptors may play an important role in the activation of a number of brain regions by orexin (OX). We hypothesized that OX and NMDA receptors may interact with cerebrocortical noradrenergic neuron originating from the locus coeruleus (LC). To test this hypothesis, using rats as experimental animals, we examined (i) in vitro effects of MK801 on OXA-evoked norepinephrine release from rat cerebrocortical slices, (ii) in vivo interaction between OXA and the NMDA receptor antagonist, MK801 on norepinephrine release from the prefrontal cortex assessed using microdialysis and (iii) MK801 and OXA-modulation of the electroencephalogram (EEG). We have found that MK801 produced a concentration-dependent inhibition of OXA-evoked norepinephrine release from rat cerebrocortical slices with the IC(50) of 0.9 microM. Moreover, we have also found that icv OXA dose-dependently stimulated norepinephrine release from the rat prefrontal cortex saturating at 213% of baseline. In addition, ip MK801 0.1 mg/kg also significantly increased norepinephrine release in prefrontal cortex to 213%. However, these increases in norepinephrine release were significantly reduced by approximately 70% by simultaneous administration of icv OXA 1 nmol and ip MK801 0.1 mg/kg. Both OXA and MK801 decreased sleep and increased wakefulness, but co-administration caused a return to base-line sleep state. These findings strongly indicate that there is a significant interaction between orexinergic neurons and NMDA receptors in the control of LC-cerebrocortical noradrenergic activity.
Brain research 11/2008; 1250:81-7. · 2.46 Impact Factor
-
Tomoko Ono,
Yoko Kawaguchi, Mihoko Kudo,
Tetsuya Kushikata,
Eiji Hashiba,
Hitoshi Yoshida,
Tsuyoshi Kudo,
Kenichi Furukawa,
Stephen A Douglas,
Remo Guerrini,
Girolamo Calo,
Kazuyoshi Hirota
[show abstract]
[hide abstract]
ABSTRACT: Urotensin II (UII) has been reported to modulate rapid eye movement (REM) sleep via activation of brainstem cholinergic neurons and REM sleep is regulated by locus coerleus (LC)-cerebrocortical noradrenergic neurons. We hypothesized that UII may activate LC-cerebrocortical noradrenergic neurons. To test this hypothesis, we have examined the effects of UII on norepinephrine release from rat cerebrocortical slices. In addition, the effect of the putative UT receptor antagonist [Pen(5), DTrp(7), Dab(8)]UII(4-11) (UFP-803) was assessed. We have compared this with other wakefulness-promoting neurotransmitters such as dopamine, glutamate, serotonin and histamine. We also studied the effects of UII and UFP-803 on intracellular Ca(2+) ([Ca(2+)]i) in HEK293 cells stably expressing rat UT receptor (HEK293-rUT cells). UII produced a time- (peaking at approximately 10 min following stimulation with 10nM) and concentration-dependent increase in norepinephrine release with pEC(50) and E(max) (% of basal) values of 8.78+/-0.17 (1.65 nM) and 138+/-2%, respectively. UII also evoked dopamine, serotonin and histamine release with similar pEC(50) values. UII increased glutamate release but only at high concentrations (<100 nM) and this failed to saturate. UII markedly increased [Ca(2+)](i) in HEK293-rUT cells in a concentration-dependent manner with pEC(50) of 8.26+/-0.24. The UT antagonist UFP-803 reversed both UII-increased norepinephrine release from the cerebrocortical slices (pK(B)=8.98) and [Ca(2+)](i) (pK(B)=8.87) in HEK293-rUT cells. Collectively these data suggest that UII evokes the release of norepinephrine via UT receptor activation and produces similar effects on other wakefulness-promoting neurotransmitters: these neurochemical actions of UII may be important for the control of the sleep-wake cycle.
Neuroscience Letters 09/2008; 440(3):275-9. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Orexins (OXs) stimulate sympathetic nerve activity to increase arterial pressure (AP) and heart rate (HR). We have previously reported that the OX(1)-receptor antagonist SB-334867 reversed the sympathomimetic actions of orexin A (OXA). In the present study we have investigated the role(s) of the orexinergic system in sympathetic activation during haemorrhage in rats. Sixteen Wistar rats, anaesthetised with pentobarbital, were assigned to 2 groups: saline i.p. (group S) and SB-334867 30 mg/kg i.p. (group SB) n=8 each. Haemorrhagic shock was established by acute withdrawal of 10 ml/kg of blood via an arterial catheter three times with a 30 min interval between each withdrawal. Haemodynamics were assessed 30 min after 10, 20, and 30 ml/kg of blood withdrawal. In addition, plasma orexin A and catecholamine concentrations in the shed blood were determined. In both groups, mean AP (MAP) and HR decreased significantly. Plasma catecholamine concentrations significantly increased following blood withdrawal. The reduction in MAP/HR and elevation of catecholamine levels were dependent on the total amount of shed blood. There were no differences between the groups. Plasma OXA concentrations increased to a greater extent in group SB than group S in response to haemorrhage. There was a significant correlation between plasma catecholamines and %change in MAP (epinephrine: r=0.553, p=0.0001, norepinephrine: r=0.374, p=0.0087) and HR (epinephrine: r=0.403, p=0.005, norepinephrine: r=0.436, p=0.002). There was no correlation with plasma orexin A levels. These data suggest that despite a weak activation the orexinergic system is unlikely to make a major contribution to the response to haemorrhage.
Neuroscience Letters 03/2008; 432(2):162-6. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous reports suggest that complete tolerance to H2 receptor antagonists (H2RAs) in patients with regular H2RA medication may be due to hypergastrinemia-increased histamine synthesis or upregulation of H2 receptors. As proton pump inhibitors (PPIs) have been reported to induce hypergastrinemia (similar to H2RAs), patients receiving long-term medication with PPIs may show tolerance to preanesthetic H2RA. Therefore, we studied the efficacy of an H2RA, roxatidine, in patients receiving long-term PPI medication.
Effects of H2RA in 15 surgical patients receiving a regular PPI for more than 4 weeks (PPI+H2RA group) were compared with those in 30 patients not receiving regular PPIs or H2RAs (None+H2RA group and None+None group, n = 15 each). Oral roxatidine was given to both PPI+H2RA and None+H2RA group patients as an anesthetic premedication, while it was not given to None+None group patients. Gastric volume and pH were measured after induction of anesthesia.
Gastric pH and volume (ml) in the PPI+H2RA group (5.79 +/- 1.61 and 9.1 +/- 16.7, respectively) were both similar to those in the None+H2RA group (5.54 +/- 2.20 and 9.7 +/- 10.8, respectively) but were significantly higher (gastric pH) and lower (volume) than in the None+None group (2.29 +/- 1.84 and 29.3 +/- 22.8, respectively, P < 0.01).
These data suggest that long-term PPI medication may not induce a tolerance to H2RAs.
Journal of Gastroenterology 04/2007; 42(4):275-8. · 4.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: As orexinergic (OXergic) neurons have been reported to mediate emotional changes, benzodiazepines might interact with OXergic neurons.
We examined the interactions between OXergic neurons and benzodiazepine receptors in orexin-A (100 nM) and K+ (25 mM)-evoked norepinephrine release from rat cerebrocortical slices.
Midazolam, diazepam, and flunitrazepam concentration-dependently inhibited both OX-A- and K+-evoked norepinephrine release. The IC50 of midazolam for orexin-A-evoked release (0.87 microM, P < 0.01), which was insensitive to flumazenil, was significantly lower than that of diazepam and flunitrazepam (around 60 microM), whereas the IC50s for K+-evoked release were not different among the benzodiazepines.
There may be no interaction between OXergic neurons and central benzodiazepine receptors.
Anesthesia and analgesia 03/2007; 104(2):338-40. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Measurement of stress hormones is a common objective method for assessment of mental stress. However, the stress of blood sampling alone may also increase stress hormone levels. In the present study, we sampled salivary biomarkers from healthy volunteers under noninvasive conditions and determined their efficacy to assess mental stress. Specifically, we examined the relationship between State Anxiety Inventory score (STAI-s) in subjects exposed to arithmetic stress and salivary chromogranin-A, alpha-amylase, or cortisol. The STAI-s was significantly correlated to salivary alpha-amylase (r = 0.589; P < 0.01) but not to salivary chromogranin-A or cortisol. Therefore, salivary alpha-amylase is a useful indicator of psychosocial stress.
Anesthesia & Analgesia 12/2005; 101(6):1873-6. · 3.29 Impact Factor
