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K Hirota

Publications and source records attributed to K Hirota.

At least 181 records · Page 10Linked to original sources
PubMed1997

Adult T cell leukemia (ATL)-derived factor/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion: possible involvement of thiol-mediated redox regulation in apoptosis caused by pro-oxidant state.

Thiol compounds, such as L-cysteine and glutathione (GSH), play crucial roles in the regulation of lymphocyte proliferation. In this study, we analyzed the effect of L-cystine and GSH depletion on lymphocyte survival and investigated the regulatory roles of adult T cell leukemia (ATL)-derived factor (ADF)/human thioredoxin (hTRX) in relation to these low m.w. thiols. MT-1, MT-2, and Jurkat cells underwent apoptosis when cultured in the L-cystine- and GSH-free medium within 18 to 24 h. Dichlorofluorescin oxidation assay indicated that the apoptosis in MT-1 and MT-2 cells was preceded by an increase in the level of intracellular hydrogen peroxide (H2O2). The addition of catalase and recombinant ADF/hTRX (rADF) partially blocked the apoptosis in a dose-dependent manner. rADF has been also shown to enhance the internalization of L-cystine into MT-2 cells in a dose-dependent manner, whereas oxidized rADF or mutated rADF that has no insulin-reducing activity failed to do so. Furthermore, culture in the L-cystine- and GSH-free medium lowered the cellular GSH content of PHA blasts, which was restored dose-dependently by rADF. These data suggest that the inability to neutralize oxidative stress results in the apoptosis of lymphoid cells under L-cystine- and GSH-depleted conditions. The protective effects of rADF may be explained by direct scavenging action on H2O2 (catalase-like activity) or by indirect neutralizing effects on the pro-oxidant status through enhancing the L-cystine internalization and elevating the intracellular GSH content.

Apoptosis↗
PubMed1997

A comparative study of L-type voltage sensitive Ca2+ channels in rat brain regions and cultured neuronal cells.

Radioligand binding studies using the L-type voltage sensitive Ca2+ channel (VSCC) antagonist (+)-[3H]PN200-110 revealed the following rank order channel density in rat brain and cultured neuronal cell homogenates: striatum > or = cerebrocortex > > cerebellum = brainstem > SH-SY5Y cell line > NG108-15 cell line > 1321N1 cell line > PC12 cell line. There were no significant differences in the equilibrium dissociation constant, Kd for (+)-[3H]PN200-110 or pK50 for nifedipine. K+ depolarization in SH-SY5Y cells and NG108-15 cells evoked a biphasic and monophasic increase in [Ca2+]i. The L-type Ca2+ channel antagonist nifedipine (1 microM) produced a 66 and 87% inhibition of the K(+)-evoked rise in the peak and plateau phase [Ca2+]i in SH-SY5Y cells and abolished the monophasic response in NG108-15 cells. The L-channel activator S(-)Bay K 8644 (1 microM) enhanced the K(+)-evoked increase in [Ca2+]i in both cell lines. These data demonstrate a comparatively low density of L-VSCC in undifferentiated SH-SY5Y cells, NG108-15 cells, 1321N1 cells and PC12 cells that are functionally active in at least SH-SY5Y cells and NG108-15 cells.

Animals↗
PubMed1997

Molecular cloning and characterization of a putative neural calcium channel alpha1-subunit from squid optic lobe.

The complete amino acid sequence of a putative calcium channel alpha1-subunit, SQCC1, from the optic lobe of the squid Loligo bleekeri has been deduced by cloning and sequence analysis of the complementary DNA. The open reading frame encodes 2206 amino acids, which corresponds to a molecular weight of 251,451. The deduced amino acid sequence shares general structural features with the other voltage-dependent calcium channels; it consists of four repeated units of homology. Each motif has five hydrophobic segments and one positively charged segment. The transcriptional products were detected in all nervous systems examined; optic lobe, cerebral ganglia and giant stellate ganglia. However, it was not detected in the mantle muscle, heart and stomach, indicating SQCC1 is a calcium channel alpha1-subunit specific for squid nervous system. SQCC1 is more closely related in its amino acid sequence patterns to dihydropyridine-insensitive calcium channels rather than dihydropyridine-sensitive ones.

Amino Acid Sequence↗
PubMed1997

Continuous haemodiafiltration during and after cardiopulmonary bypass in renal failure patients.

PURPOSE: Continuous haemodiafiltration (CHDF) is a technique enhancing the efficiency of solute clearance of haemofiltration by infusing dialysis fluid through the haemofilter. It has been reported to control water and electrolyte balance continuously without haemodynamic instability in critically ill patients with renal failure, Therefore, we used CHDF during and after cardiopulmonary bypass (CPB) in two renal failure patients, and discuss its efficacy. CLINICAL FEATURES: The first patient undergoing aortic valve replacement had dialysis-dependent renal failure. Chronic renal failure in the second patient undergoing mitral valve replacement and coronary revascularization was controlled preoperatively with diuretics. In both cases, CHDF was performed not only during CPB but also in the post-CPB period. Serum concentrations of potassium, urea and creatinine were well-controlled in spite of large amount of blood transfused in the post-CPB period (1000 ml fresh blood and 400 ml fresh frozen plasma in the fist patient, and 1400 ml fresh blood in the second patient). There was no difficulty in haemostasis during the use of nafamostat mesilate as an anticoagulant to keep activated clotting time at about 150 sec for CHDF in the post-CPB period. CONCLUSION: Our initial experiences of CHDF during and after CPB suggest that the technique provides excellent electrolyte, metabolite and fluid management for the cardiac patients with chronic renal failure. Combined with nafamostat mesilate for anticoagulation, CHDF was simple and safe and did not increase the risk of bleeding.

Adult↗
PubMed1997

Midazolam reverses histamine-induced bronchoconstriction in dogs.

PURPOSE: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. METHODS: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. RESULTS: Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. CONCLUSION: Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.

Anesthetics, Intravenous↗
PubMed1997

Pituitary folliculo-stellate-like cell line produces a cytokine-induced neutrophil chemoattractant.

In previous studies, we reported that cytokine-induced neutrophil chemoattractant (CINC) was produced in the pituitary gland. Here we investigated the possibility of detection of CINC immunoreactivity in the pituitary folliculo-stellate (FS)-like cell line (TtT/GF). Intense immunoreactivity was observed by immunocytochemistry in the cytoplasm and cell processes of TtT/GF cells. CINC immunoreactivity was detected by an enzyme-linked immunosorbent assay in as little as 3 h after conditioning the medium with TtT/GF cells, and it increased significantly in a time-dependent manner during the first 24 h of the culture. This immunoreactivity could be induced by lipopolysaccharide and tumor necrosis factor-alpha in a time- and dose-dependent manner. We also observed the expression of CINC mRNA in TtT/GF cells and LPS increased CINC mRNA accumulation in TtT/GF cells. These findings indicate that CINC produced by FS cells may play a role as a paracrine factor of the anterior pituitary gland, and TtT/GF will provide a useful model system for studying the regulation of CINC secretion by FS cells.

Animals↗
PubMed1997

Characterization of serotype II polysaccharide antigen of group E streptococci using a monoclonal antibody.

A Monoclonal antibody (MAb II-T) specific for serotypes II and V Group E streptococci (GES) was prepared by fusing myeloma cells with spleen cells of mice immunized with whole cells of a serotype II strain. MAb II-T reacted in an enzyme immunoassay (EIA) with whole cells of both serotypes and reacted in gel diffusion test with autoclaved-saline extraction of serotypes II and V. The extract was purified by DEAE-Sephadex A-25, followed by treatment with proteinase K, and further by chromatography with a Sephadex G-200 column. The purified polysaccharide (PS) antigen contained 98.6% carbohydrate and 1.4% protein, but no detectable phosphorus. In hapten inhibition tests using various sugars, D-mannosamine markedly inhibited the precipitin reaction. These results indicated that the antigenic determinant might have a structure similar to D-mannosamine.

Antibodies, Bacterial↗
PubMed1997

The effects of recombinant rat mu-opioid receptor activation in CHO cells on phospholipase C, [Ca2+]i and adenylyl cyclase.

1. The rat mu-opioid receptor has recently been cloned yet its second messenger coupling remains unclear. The endogenous mu-opioid receptor in SH-SY5Y cells couples to phospholipase C (PLC), increases [Ca2+]i and inhibits adenylyl cyclase (AC). We have examined the effects of mu-opioid agonists on inositol(1,4,5)trisphosphate (Ins(1,4,5)P3), [Ca2+]i and adenosine 3':5'-cyclic monophosphate (cyclic AMP) formation in Chinese hamster ovarian (CHO) cells transfected with the cloned mu-opioid receptor. 2. Opioid receptor binding was assessed with [3H]-diprenorphine ([3H]-DPN) as a radiolabel. Ins(1,4,5)P3 and cyclic AMP were measured by specific radioreceptor assays. [Ca2+]i was measured fluorimetrically with Fura-2. 3. Scatchard analysis of [3H]-DPN binding revealed that the Bmax varied between passages. Fentanyl (10 pM 1 microM) dose-dependently displaced [3H]-DPN, yielding a curve which had a Hill slope of less than unity (0.6 +/- 0.1), and was best fit to a two site model, with pK1 values (% of sites) of 9.97 +/- 0.4 (27 +/- 4.8%) and 7.68 +/- 0.07 (73 +/- 4.8%). In the presence of GppNHp (100 microM) and Na+ (100 mM), the curve was shifted to the right and became steeper (Hill slope = 0.9 +/- 0.1) with a pK1 value of 6.76 +/- 0.04. 4. Fentanyl (0.1 nM-1 microM) had no effect on basal, but dose-dependently inhibited forskolin (1 microM)-stimulated, cyclic AMP formation (pIC50 -7.42 +/- 0.23), in a pertussis toxin (PTX; 100 ng ml-1 for 24 h)-sensitive and naloxone-reversible manner (K1 = 1.7 nM). Morphine (1 microM) and [D-Ala2, MePhe4, gly(ol)5]-enkephalin (DAMGO, 1 microM) also inhibited forskolin (1 microM)-stimulated cyclic AMP formation, whilst [D-Pen2, D-Pen5], enkephalin (DPDPE, 1 microM) did not. 5. Fentanyl (0.1 nM-10 microM) caused a naloxone (1 microM)-reversible, dose-dependent stimulation of Ins(1,4,5)P3 formation, with a pEC50 of 7.95 +/- 0.15 (n-5), PTX (100 ng ml-1 for 24 h) abolished, whilst Ni2 (2.5 mM) inhibited (by 52%), the fentanyl-induced Ins(1,4,5)P3 response. Morphine (1 microM) and DAMGO (1 microM), but not DPDPE (1 microM), also stimulated Ins(1,4,5)P3 formation. Fentanyl (1 microM) also caused an increase in [Ca2+]i (80 +/- 16.4 nM, n-6), reaching a maximum at 26.8 +/- 2.5 s. The increase in [Ca2+]i remained elevated until sampling ended (200 s) and was essentially abolished by the addition of naloxone (1 microM). Pre-incubation with naloxone (1 microM, 3 min) completely abolished fentanyl-induced increases in [Ca2+]i. 6. In conclusion, the cloned mu-opioid receptor when expressed in CHO cells stimulates PLC and inhibits AC, both effects being mediated by a PTX-sensitive G-protein. In addition, the receptor couples to an increase in [Ca2+]i. These findings are consistent with the previously described effector-second messenger coupling of the endogenous mu-opioid receptor.

Adenylyl Cyclases↗
PubMed1997

Sevoflurane modulates both GABAA and GABAB receptors in area CA1 of rat hippocampus.

It has been suggested that volatile anaesthetics enhance synaptic inhibition via gamma-aminobutyric acid (GABA) in the central nervous system. We have examined the effects of sevoflurane on GABAA and GABAB receptors in rat hippocampus in vitro. Extracellular recordings were used to record field potentials in rat CA1 pyramidal neurones of transverse hippocampal slices, stimulated electrically via stratum radiatum input. Sevoflurane 0.4-5.0 vol% decreased the amplitudes of population spikes (PS) of CA1 neurones in a concentration-dependent (calculated ED50 = 6.31 vol%) and reversible manner. The GABAA antagonist, bicuculline methiodide 5 x 10(-5) mol litre-1, induced oscillations (multiple spikes) and blocked the inhibitory actions of sevoflurane in the initial component (up to 24.8 ms) of the oscillation. The latter portion of the oscillation (greater than 24.8 ms) was depressed by sevoflurane. The GABAB antagonist, phaclofen 5 x 10(-4) mol litre-1 partially blocked the effects of sevoflurane on the latter portion of the bicuculline-induced oscillation. Sevoflurane 2.0 vol% significantly enhanced paired-pulse (PS2/PS1) facilitation (from 128.4% to 155.5% at an inter-stimulus interval of 37.9 ms); this enhancement was blocked by phaclofen. Stimulus-response relationships revealed that 2.0 vol% sevoflurane increased the intensity of threshold for PS generation to 109.8% of control. Both the GABAA agonist, muscimol 2 x 10(-5) mol litre-1 and the GABAB agonist, (+/-)-baclofen 10(-5) mol litre-1, potentiated the effects of sevoflurane. Sevoflurane enhanced thresholds by 137.1% and 138.5% of control in the presence of muscimol and (+/-)-baclofen, respectively. The results demonstrate that sevoflurane at clinical concentrations activated both GABAA- and GABAB-mediated inhibitions in area CA1 of the hippocampus, and that sevoflurane and GABA agonists (muscimol and baclofen) acted on different domains on the GABAA and GABAB receptors, respectively.

Anesthetics, Inhalation↗
PubMed1997

Do local anaesthetics interact with dihydropyridine binding sites on neuronal L-type Ca2+ channels?

We have examined the interaction of procaine, prilocaine, lignocaine, bupivacaine, amylocaine and R(+) and S(-) ropivacaine with L-type voltage-sensitive Ca2+ channels in rat cerebrocortical membranes. Membranes were prepared in Tris HCl 50 mmol litre-1, pH 7.4, by homogenization and centrifugation. Binding assays were performed in 1-ml volumes of Tris HCl 50 mmol litre-1, pH 7.4, for 90 min at room temperature using approximately 200 micrograms of protein. Non-specific binding was defined in the presence of nifedipine 10(-5) mol litre-1, and bound and free radioactivity were separated by vacuum filtration. The effects of local anaesthetics were determined by displacement of [3H]PN200-110 (approximately 0.2 nmol litre-1), a radiolabelled 1,4- dihydropyridine (DHP) L-channel antagonist. The concentration of displacer producing 50% displacement was corrected for the competing mass of [3H]PN200-110 to yield the affinity constant, K50. All local anaesthetics displaced [3H]PN200-110 in a dose-dependent manner with a rank order potency of (K50, mmol litre-1) bupivacaine (0.48), amylocaine (0.74), lignocaine (1.09), prilocaine (2.06) and procaine (2.09). Ropivacaine enantiomers did not show stereo-selective displacement, with K50 values of 0.99 and 0.92 mmol litre-1 for R(+) and S(-) ropivacaine, respectively. There was a significant correlation between pK50 and p (octanol:buffer partition coefficient) (r2 = 0.872, P = 0.020), pK50 and p (local anaesthetic potency) (r2 = 0.816, P = 0.036), pK50 and p (relative conduction blocking potency) (r2 = 0.843, P = 0.028) and between pK50 and p (IC50 for inhibition of cardiac output) (r2 = 0.897, P = 0.015). These data suggest that DHP binding sites may be involved in both the mechanism of local anaesthesia and the cardiotoxicity of these agents.

Anesthetics, Local↗
PubMed1997

In vivo assessment of droperidol-induced bronchial relaxation in dogs using a superfine fibreoptic bronchoscope.

Droperidol has been reported to cause bronchodilatation but its mechanism(s) of action is unknown. We have evaluated the spasmolytic effect of droperidol on histamine- and serotonin (5-HT)-induced bronchoconstriction in dogs. Bronchial cross-sectional area was assessed with a superfine fibreoptic bronchoscope. Twenty-eight mongrel dogs were allocated randomly to one of two groups (histamine and 5-HT) to receive either histamine or 5-HT to induce bronchoconstriction. Changes in bronchial cross-sectional area were presented as percentage of basal bronchial cross-sectional area. Continuous i.v. infusion of histamine 500 micrograms kg-1 h-1 or 5-HT 500 micrograms kg-1 h-1 decreased percentage bronchial cross-sectional area by 46.4 (14.3)% or 68.9 (13.7)%, respectively. In both groups, droperidol reversed bronchoconstriction in a dose-dependent manner. In the histamine but not in the 5-HT group, plasma adrenaline and noradrenaline concentrations increased significantly after i.v. droperidol. In addition, propranolol antagonized droperidol-induced relaxation in the histamine but not in the 5-HT group. Our data indicate that the spasmolytic effect of droperidol on canine airway was caused, at least in part, by both catecholamine releases and 5-HT receptor antagonism.

Animals↗
PubMed1997

Measurement of bronchodilatation using a superfine fibreoptic bronchoscope.

In this study, we report the development and accuracy of a direct technique to measure airway calibre using a superfine fibreoptic bronchoscope. Ten mongrel dogs were anaesthetized with pentobarbitone and the trachea intubated with a tracheal tube; the small lumen of the tube allowed passage of a superfine fibreoptic bronchoscope (od 2.2 mm). Bronchial cross-sectional area and airway pressure were recorded continuously and dynamic pulmonary compliance and airway resistance calculated. The dogs were allocated to one of two groups. In the first group (six dogs), bronchoconstriction was induced with histamine 10 micrograms kg-1 i.v. and 500 micrograms kg-1 h-1 c.i.v. Thirty minutes later, adrenaline 0-0.4 mg kg-1 was given i.v. Bronchial cross-sectional area, dynamic pulmonary compliance and airway resistance were assessed simultaneously. In the second group, 0.9% saline was given 30 min after placement of the superfine fibreoptic bronchoscope and 10 min later atropine 0.1 microgram kg-1 was administered. In the first group, histamine decreased mean percentage bronchial cross-sectional area by 49.2 (SD 11.5) %, reduced dynamic pulmonary compliance from 32.1 (12.6) to 22.3 (5.2) ml cm H2O-1 and increased airway resistance from 39.1 (11.6) to 57.2 (10.2) cm H2O litre-1 s-1. Adrenaline produced a dose-dependent increase in percentage bronchial cross-sectional area and dynamic pulmonary compliance to 119.4 (31.3)% and 27.4 (5.5) ml cm H2O-1, respectively, and a decrease in airway resistance to 43.9 (7.2) cm H2O litre-1 s-1. There were significant correlations between percentage bronchial cross-sectional area and dynamic pulmonary compliance (r = 0.720, P < 0.0001) and airway resistance (r = 0.727, P < 0.0001). Atropine 0.1 mg kg-1 increased basal bronchial cross-sectional area to 137.5 (16.9) %. These data indicate that adrenaline reversed histamine- and pentobarbitone-induced bronchoconstriction.

Airway Resistance↗
PubMed1997

Studies on the binding of [3H]amethocaine to rat cerebrocortical membranes.

We have examined the binding of the local anaesthetic agent [3H]amethocaine to rat cerebrocortical membranes. All studies were performed in Tris buffer 50 mmol litre-1 at pH 7.4. Bound and free radioligand were separated by rapid vacuum filtration. [3H]Amethocaine binding at room temperature was dose-dependent and saturable, with mean Kd and Bmax values of 153 (SEM 18) nmol litre-1 and 9.4 (1.6) pmol/mg protein, respectively. [3H]Amethocaine binding was displaced in a dose-dependent manner (pIC50) by unlabelled amethocaine (6.89), procaine (5.20), lignocaine (3.46) and prilocaine (2.81). Ropivacaine and bupivacaine did not produce 50% displacement at the highest concentrations used (10(-4) and 10(-3) mol litre-1, respectively). We examined the nature of the binding site further with a range of ion channel antagonists (nifedipine, verapamil, diltiazem, omega-conotoxin, tetrodotoxin, tetraethylammonium and 4-aminopyridine) and ion channel coupled receptor ligands (L-glutamate, MK801, GABA, glycine and nicotine). With the exception of tetraethylammonium (pIC50 3.07) and 4-aminopyridine (pIC50 3.68), all non-anaesthetic agents failed to displace [3H]amethocaine. Collectively our data suggest that it is unlikely that there is a single target site for all local anaesthetic agents.

Anesthetics, Local↗
PubMed1997

Thioredoxin expression in the human endometrium during the menstrual cycle.

Human thioredoxin, a cellular disulphide reducing protein, is known to be secreted by some types of cells and to display unique extracellular activities including modulation of cytokine actions and protection of the cell against damage from oxidative stress. This study has been undertaken to investigate the pattern of expression and tissue distribution of thioredoxin in human endometrium during the menstrual cycle. Immunohistochemical studies showed increased thioredoxin immunoreactivity in the glands of the secretory phase compared to those of the proliferative phase. Although the staining of thioredoxin was relatively intense in predecidual stromal cells, the most prominent staining of thioredoxin was present in both glands and stroma of the endometrium in the early secretory phase of the menstrual cycle. Northern hybridization analyses revealed that expression of thioredoxin mRNA in the endometrium of the early secretory phase was approximately 3-fold compared to the other phases of the menstrual cycle, consistent with the results of the immunohistochemical studies. These results suggest that both protein and gene expression of thioredoxin in the endometrium are menstrual cycle phase-specific and highly active in the phase of endometrial differentiation which occurs in preparation for implantation (early secretory phase of the menstrual cycle). Thioredoxin expressed in the early secretory phase of the menstrual cycle may be advantageous for blastocyst implantation.

Endometrium↗
PubMed1997

The relaxant effect of ketamine on guinea pig airway smooth muscle is epithelium-independent.

Airway epithelial cells and vascular endothelial cells modulate the tone of the underlying smooth muscle by releasing relaxing factors such as prostanoids and nitric oxide (NO). In the present study, we investigated whether the relaxant effect of ketamine depends on any of the epithelium-derived relaxing factors. Tracheae of female guinea pigs were cut spirally into strips (15 x 3 mm) and mounted in water-jacketed organ baths filled with Krebs-bicarbonate buffer aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. Changes in the tension of the strips were measured isometrically with a force displacement transducer and recorded with a polygraph. In the first set of experiments, we examined the effect of ketamine on the concentration-response curves for histamine and carbachol in strips in which the epithelium was kept intact and in strips with denuded epithelium. In the second and third set of experiments, we studied the effect of indomethacin, a cyclooxygenase inhibitor, and N-omega-nitro-L-arginine methylester(L-NAME), a NO synthase inhibitor, on the relaxant activity of ketamine on tracheal strips contracted by histamine or carbachol. The following results were obtained: 1. Mechanical denudation of the tracheal epithelium shifted the concentration-response curve for histamine to the left (the 50% effective concentration [EC50] value of histamine decreased from 3.5 +/- 0.02 x 10(-6) M in the intact strips to 0.98 +/- 0.01 x 10(-6) M in denuded strips, P < 0.001). However, removal of the tracheal epithelium did not change the response to carbachol (the EC50 for carbachol was 1.1 +/- 0.02 x 10(-7) M in intact strips versus 0.88 +/- 0.01 x 10(-7) M after epithelial removal, P > 0.05). 2. Ketamine shifted to the right the concentration-response curves for histamine and carbachol in both intact and denuded tracheae. 3. Indomethacin did not alter the relaxant effect of ketamine on the tracheae contracted by either histamine (the concentration that inhibits 50% [IC50] of ketamine = 1.5 +/- 0.01 x 10(-3) M in control strips and 1.3 +/- 0.04 x 10(-3) M in strips pretreated with indomethacin, P > 0.05) or carbachol (the IC50 of ketamine was 2.5 +/- 0.02 x 10(-4) M in control strips and 2.4 +/- 0.01 x 10(-4) M in strips pretreated with indomethacin, P > 0.05). 4. L-NAME did not influence the relaxant effect of ketamine on tracheae contracted by either histamine (the IC50 of ketamine = 1.6 +/- 0.05 x 10(-3) M in control strips and 1.6 +/- 0.05 x 10(-3) M in strips pretreated with L-NAME, P > 0.05) or carbachol (the IC50 of ketamine = 2.6 +/- 0.04 x 10(-4) M in control strips and 2.3 +/- 0.01 x 10(-4) M in trips pretreated with L-NAME, P > 0.05). These results indicate that neither the mechanical removal of the tracheal epithelium nor the blockade of the release of potent mediators from tracheal epithelial cells influence the relaxant effect of ketamine on guinea pig tracheal strips contracted by histamine or carbachol. We conclude that ketamine relaxes the airway smooth muscle by an epithelium-independent mechanism.

Airway Resistance↗
PubMed1997

Uric acid excretion increases during propofol anesthesia.

We compared the effect of propofol with that of sevoflurane anesthesia on uric acid (UA) excretion in ASA physical status I and II patients with normal renal function. A propofol group (n = 11) received propofol-nitrous oxide-fentanyl after induction of anesthesia by propofol, while a sevoflurane group (n = 12) received sevoflurane-nitrous oxide-fentanyl after induction of anesthesia by thiamylal. UA, creatinine (Cr), and urea nitrogen concentrations in serum and urine were measured before induction of anesthesia, 1, 2, and 3 h after induction, and on Postoperative Day 1. N-acetyl-beta-D-glucosaminidase, beta2-microglobulin concentrations, and pH in urine were also examined. Plasma clearance of UA (CUA) and Cr (CCr) were calculated. The hourly concentration and excretion of urine UA were significantly higher than those of the sevoflurane group (P < 0.01). Significant correlations were noted between the hourly urine volume and UA concentration (r = 0.58, P < 0.01 for the propofol group; r = 0.51, P < 0.01 for the sevoflurane group). The CUA of the propofol group was significantly higher than that of the sevoflurane group (22.9 +/- 10.6 vs 5.9 +/- 3.4 mL/min, mean +/- SD, P < 0.05). There were no significant differences in other renal variables between the two groups. The present study demonstrated that the UA excretion increased during propofol anesthesia, while it remained stable during sevoflurane anesthesia.

Anesthetics, Combined↗
PubMed1997

The effects of sevoflurane on population spikes in CA1 and dentate gyrus of the rat hippocampus in vitro.

UNLABELLED: We studied the effects of sevoflurane on population spikes (PSs) in two synaptic pathways in rat hippocampal slices. Stimulating electrodes were placed on Schaffer collateral fibers or perforant path to activate inputs to CA1 pyramidal neurons or dentate gyrus (DG) neurons, respectively. Extracellular glass microelectrodes were used to record PSs. The paired-pulse stimulus was used to induce the paired-pulse facilitation (PPF). Sevoflurane (0.4-5.0 vol%) significantly decreased the amplitudes of PSs of CA1 and DG in a dose-dependent and reversible manner (25% effective dose values were 4.1 and 0.9 vol%, respectively). The stimulus-response relationships for PS amplitudes revealed that sevoflurane increased the threshold for PS generation in CA1 and DG. Sevoflurane (2.0 vol%) significantly enhanced PPF from 127% and 263% to 153% and 494% in CA1 and DG, respectively. The results imply that the effects of sevoflurane on PSs are greater in DG than in CA1 neurons, that sevoflurane enhances the PPF in both CA1 and DG, and that the actions of sevoflurane are not similar to those of other volatile or intravenous anesthetics previously reported in hippocampal preparations. IMPLICATIONS: The volatile anesthetic sevoflurane alters neural excitability of individual pathways in the hippocampus in a manner different from other general anesthetics. The results are consistent with a site-specific mechanism of action for general anesthesia.

Anesthetics, Inhalation↗