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Biomedical subjects

A Nagata

Publications and source records attributed to A Nagata.

At least 37 records · Page 2Linked to original sources
PubMed2000

Localization of oxidized HDL in atheromatous plaques and oxidized HDL binding sites on human aortic endothelial cells.

We examined the localization of oxidized high-density lipoprotein (HDL) in atheromatous plaques and the oxidized HDL binding sites on endothelial cells. Histochemical analysis using CuSO4-oxidized HDL-specific 9F5-3a antibody indicated the presence of oxidized HDL in the intima of atheromatous plaques in human abdominal aortae. The cell surface binding of 125I-oxidized HDL to cultured human aortic endothelial cells (HAEC) was saturable, with an apparent dissociation constant (Kd) of 1.43 micromol/L. Competition for 125I-oxidized HDL binding was strong for oxidized HDL, moderate for native HDL and low for acetylated low-density lipoprotein (LDL) or oxidized LDL. Using oxidized HDL as a ligand for blotting, a major 130-kDa band was detected in HAEC. These results suggest that oxidized HDL and its putative binding protein are present in atheromatous plaques and endothelial cells, respectively.

Antibodies, Monoclonal↗
PubMed1999

Oncogenic stimulation recruits cyclin-dependent kinase in the cell cycle start in rat fibroblast.

The rat fibroblast NRK cells are transformed reversibly by a combination of growth factors. When stimulated with serum, NRK cells rely on cyclin-dependent kinase 4 (Cdk4) for their S phase entry. However, when stimulated with serum containing oncogenic growth factors, they come to rely on either Cdk4 or Cdk6, and their S phase entry cannot be blocked unless both Cdk4 and Cdk6 are immunodepleted. Such change of dependence does not occur in the NRK cell mutants defective in an oncogenic signal pathway and, therefore, deficient in anchorage-independent cell cycle start ability, correlating Cdk6 dependence with this remarkable, cancer-associated phenotype. However, both Cdk4 and Cdk6 are activated upon serum stimulation, and neither the amounts of Cdk6, Cdk4, cyclin D1, and cyclin-dependent kinase inhibitors nor the activities or subcellular localization of Cdk6 and Cdk4 are significantly influenced by oncogenic stimulation. Thus, oncogenic stimulation invokes Cdk6 to participate in a critical step of the cell cycle start in a rat fibroblast, but by a mechanism seemingly unrelated to the regulation of the kinase. Given that many hematopoietic cells employ predominantly Cdk6 for the cell cycle start and perform anchorage-independent growth by nature, our results raise the possibility that the oncogenic stimulation-induced anchorage-independent cell cycle start of NRK is elicited by a mechanism similar to the one used for hematopoietic cell proliferation.

Animals↗
PubMed1999

Basic study on gene therapy of human malignant glioma by use of the cationic multilamellar liposome-entrapped human interferon beta gene.

For gene therapy of human malignant glioma, we adopted positively charged multilamellar liposomes entrapping the human interferon beta (hIFN-beta) gene. One week after the transplantation of human malignant glioma U251-SP cells to produce glioma in nude mouse brain, the liposomes entrapping the gene (500 ng of DNA per 25 nmol of lipids per 2 microl) were injected into the same site of the cell transplantation once every second day for a total of five injections; and by this means the tumor completely disappeared. To confirm the antiproliferative effect of hIFN-beta, we performed an in vitro study using a plasmid containing a secretion signal sequence-deleted hIFN-beta gene and one containing the hIFN-beta gene inserted in reverse. In both cases, there was no hIFN-beta release into the medium and no growth inhibition effect. On addition of anti-hIFN-beta antibody to the medium, the growth inhibition effect was abolished. As this cell line expresses IFN-alpha/beta receptor, the hIFN-beta produced in the transfected cells could be released and acted in a paracrine manner. For 120 days the body weight change of normal mice treated by the same procedure as used in the curing experiment was not significant among the groups injected with empty liposomes, plasmid only, and liposomes entrapping the gene. In all of these three groups, death, abnormal behavior, and significant histological changes were not observed.

Animals↗
PubMed1999

Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice.

Prostaglandin (PG) D2 is the most abundant prostanoid produced in the central nervous system of mammals and has been implicated in the modulation of neural functions such as sleep induction, nociception, regulation of body temperature, and odor responses. We generated gene-knockout mice for lipocalin-type PGD2 synthase (L-PGDS) and found that the intrathecal administration of PGE2, an endogenous pain-producing substance, failed to elicit allodynia (touch-evoked pain), which is one typical phenomenon of neuropathic pain, whereas it evoked thermal hyperalgesia, in L-PGDS-/- mice. We also found that the allodynic response induced by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline was selectively abolished in the L-PGDS-/- mice, among excitatory and inhibitory agents that induced allodynia in wild-type mice. Interestingly, simultaneous injection of a femtogram amount of PGD2 with PGE2 or bicuculline induced allodynia in L-PGDS-/- mice to the same extent as in wild-type mice. The PGE2- or bicuculline-evoked allodynia in wild-type and in PGD2-supplemented L-PGDS-/- mice was blocked by a PGD2 receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD2 is essential for both PGE2- and bicuculline-induced allodynia.

Anesthesia↗
PubMed1999

Polyethylene glycol augments thyroid cAMP responses by fragments from protease-digested TSAb or TSBAb-IgG.

In the previous reports, we have demonstrated (1) that polyethylene glycol (PEG)(5%) augmented TSAb (thyroid stimulating antibody)-stimulated cAMP responses of porcine thyroid cells, and (2) that fragments from papain-digested TSBAb (thyroid stimulation blocking antibody) could stimulate thyroid cAMP synthesis. Thus, we studied the effect of 5% PEG on cAMP responses stimulated by the protease-digested TSAb- or TSBAb-fragments. Stimulatory effect of 5% PEG on cAMP production by Fab fragment (Mr 50 KDa) and the retarded fraction (Mr 20 KDa) from the gel-filtration on Sephadex G-100 using papain-digested TSAb-IgG unbound to Protein A-Sepharose was observed. Similar stimulatory effect of 5% PEG on the second fraction (Fc with trace amounts of Fab) in the gel-filtration on Sephadex G-100 using papain digested TSAb-IgG bound to Protein A-Sepharose was observed. Stimulatory effect of PEG on the second fraction was derived from Fab fragment. PEG (5%) also showed stimulatory effect on cAMP production by F(ab')2 fragment (Mr 100 KDa) from the gel-filtration on Sephadex G-100 using pepsin-digested TSAb-IgG unbound to Protein A-Sepharose. PEG (5%) augmented cAMP responses by both Fab and the retarded fractions from the gel-filtration using papain-digested TSBAb-IgG unbound to Protein A when these fractions could stimulate cAMP synthesis. In conclusion, PEG (5%) augments cAMP responses stimulated by F(ab')2, Fab and the smaller molecular components (Mr 20 KDa) separated from protease-digested TSAb-IgG. PEG also augments cAMP responses stimulated by Fab and the smaller molecular components with thyroid stimulating activity separated from papain-digested TSBAb-IgG.

Autoantibodies↗
PubMed1999

Effects of nitrous oxide on haemodynamic and electroencephalographic responses induced by tetanic electrical stimulation during propofol anaesthesia.

We studied the effect of nitrous oxide on haemodynamic and electroencephalographic responses caused by noxious stimulation during propofol anaesthesia. Thirty-four patients (ASA I-II) were anaesthetised with propofol 3 mg x kg(-1) and were randomly allocated to receive either 60% nitrous oxide in oxygen or 40% oxygen in air. Anaesthesia was maintained using propofol infusion of 10 mg x kg(-1) x h(-1) for the first 10 min, 8 mg x kg(-1) x h(-1) for the next 10 min and 6 mg x kg(-1) x h(-1) thereafter. Thirty minutes after the induction of anaesthesia, tetanic electrical stimulation (80 mA, 100 Hz) was applied to the ulnar nerve. Tetanic stimulation significantly increased blood pressure and heart rate in both groups (p < 0.005 or less), but did not induce any arousal pattern on the electroencephalograph. Nitrous oxide significantly attenuated the tetanic stimulation-induced increase in blood pressure (p < 0.05 or less), but not the heart rate.

Adult↗
PubMed1999

Electroencephalographic arousal response during tracheal intubation and laryngeal mask airway insertion after induction of anaesthesia with propofol.

Laryngoscopy and tracheal intubation, or insertion of a laryngeal mask airway may lead to an arousal response on the electroencephalogram. We studied whether more intense stimulation (laryngoscopy and tracheal intubation) causes a greater arousal response than less intense stimulation (laryngeal mask airway insertion). Thirty-four patients (ASA I-II) were anaesthetised with propofol 3 mg.kg-1, followed by vecuronium 0.15 mg.kg-1 and a propofol infusion of 10 mg.kg-1.h-1. Three minutes after induction of anaesthesia, either laryngoscopy and tracheal intubation (n = 18), or laryngeal mask airway insertion (n = 16) was performed. Laryngoscopy and tracheal intubation caused a significantly greater increase in blood pressure (but not heart rate) than laryngeal mask airway insertion (p < 0.05). Electroencephalogram responses were not different. More intense stimulation does not cause a greater arousal response during propofol anaesthesia.

Adult↗
PubMed1999

Mechanism of the augmentative effect of high polyethylene glycol (PEG) concentrations on the thyroid stimulating activity in TSAb-IgG using a porcine thyroid cell assay.

We previously demonstrated that high polyethylene glycol (PEG) concentrations (5% PEG) significantly augmented cAMP production in response to TSAb-IgG using the porcine thyroid cell (PTC) assay. The mechanism of the stimulatory effect of 5% PEG on cAMP production was examined by a two-step incubation with PTC. TSAb-IgG was preincubated with or without addition of 5% PEG in the PTC assay for 2.5 hr (1st incubation) and separated PTC was re-incubated with fresh Hank's buffer for 5 hr (2nd incubation). cAMP production in the 1st incubation medium by co-incubation of TSAb-IgG and 5% PEG for 2.5 hr was significantly increased (3.3-fold) compared to that without 5% PEG. When the cAMP content in PTC and the incubation medium were compared in the same volume of incubation medium after co-incubation of TSAb-IgG and 5% PEG for 2.5 hr, cAMP contents in PTC were about 7-fold higher than that in the incubation medium, and this ratio did not change in the incubation medium of TSAb-IgG without 5% PEG. Similar increases in cAMP contents in PTC (6.6-fold) compared to the incubation medium were also observed with bTSH, although there was no augmentative effect of 5% PEG on cAMP production by bTSH in either the incubation medium or PTC. When PTC, which had been preincubated with normal-IgG and 5% PEG in the 1st incubation, was re-incubated with TSAb-IgG in the 2nd incubation medium, cAMP production by TSAb-IgG was not stimulated by 5% PEG. The augmentative effect of 5% PEG on cAMP production by TSAb-IgG was observed whenever 5% PEG and TSAb-IgG were co-incubated in either the 1st or 2nd incubation. However, no stimulatory effect of 5% PEG on bTSH was observed. These results suggested the stimulatory effect of 5% PEG on TSAb-IgG-stimulated cAMP production may be due to the increase of binding or incorporation of TSAb-IgG into the membranes of PTC compared to TSH.

Animals↗
PubMed1999

Augmentation of thyroid-stimulating antibody-stimulated cyclic adenosine monophosphate response by polyethylene glycol, polyvinyl alcohol, and dextran; highly sensitive porcine thyroid cell thyroid-stimulating antibody assay.

Previously, we reported that 5% polyethylene glycol (PEG) (6000) augmented thyroid-stimulating antibody (TSAb)-stimulated cyclic adenosine monophosphate (cAMP) production in porcine thyroid cell (PTC) assay. This augmentation by PEG was specific to TSAb-stimulation. In this study we examined the effects of nonionic hydrophilic polymers such as PEG, polyvinyl alcohol (PVA), and dextran (DEX) on TSAb-stimulated cAMP production. We demonstrated that graded doses of PEG, PVA, and DEX augmented TSAb-stimulated cAMP productions; the prominent augmentations were observed with 5% PEG (20,000), 5% PEG (6000), 6% PEG (4000), 10% PVA, 14% DEX T-250, and 14% DEX T-70. PVA did not augment thyrotropin (TSH)-stimulated cAMP synthesis. Five percent PEG (20,000), 14% DEX T-250, and 14% DEX T-70 augmented TSH-stimulated cAMP synthesis very slightly. PEG, PVA, and DEX had no effects on the cAMP synthesis stimulated by GTPgammaS, forskolin, or pituitary adenylate cyclase activating polypeptide (PACAP), which stimulated adenylate cyclase. We also demonstrated that PEG, PVA, and DEX augmented the cAMP responses stimulated by small amounts (50 microL) of sera from Graves' patients; small amounts (50 microL) of sera could be used instead of purified immunoglobulin G (IgG). This may simplify the TSAb assay. We developed a highly sensitive simplified TSAb assay. PEG weakly augmented TSAb binding to isolated TSH receptor (thyrotropin-binding inhibitor immunoglobulin [TBII] increased slightly). The mechanisms of the augmentations of TSAb-stimulated cAMP productions by PEG, PVA, and DEX is not simply explained by increased binding of TSAb to the receptors. Some factors that enhance TSAb action at the receptor site are suggested.

Animals↗
PubMed1999

A double-strand break repair component is essential for S phase completion in fission yeast cell cycling.

Fission yeast rad22(+), a homologue of budding yeast RAD52, encodes a double-strand break repair component, which is dispensable for proliferation. We, however, have recently obtained a cell division cycle mutant with a temperature-sensitive allele of rad22(+), designated rad22-H6, which resulted from a point mutation in the conserved coding sequence leading to one amino acid alteration. We have subsequently isolated rad22(+) and its novel homologue rti1(+) as multicopy suppressors of this mutant. rti1(+) suppresses all the defects of cells lacking rad22(+). Mating type switch-inactive heterothallic cells lacking either rad22(+) or rti1(+) are viable, but those lacking both genes are inviable and arrest proliferation with a cell division cycle phenotype. At the nonpermissive temperature, a synchronous culture of rad22-H6 cells performs DNA synthesis without delay and arrests with chromosomes seemingly intact and replication completed and with a high level of tyrosine-phosphorylated Cdc2. However, rad22-H6 cells show a typical S phase arrest phenotype if combined with the rad1-1 checkpoint mutation. rad22(+) genetically interacts with rad11(+), which encodes the large subunit of replication protein A. Deletion of rad22(+)/rti1(+) or the presence of rad22-H6 mutation decreases the restriction temperature of rad11-A1 cells by 4-6 degrees C and leads to cell cycle arrest with chromosomes incompletely replicated. Thus, in fission yeast a double-strand break repair component is required for a certain step of chromosome replication unlinked to repair, partly via interacting with replication protein A.

Amino Acid Sequence↗
PubMed1999

Clinical usefulness of TSAb assay with high polyethylene glycol concentrations.

We previously demonstrated the stimulatory effect of polyethylene glycol (PEG) on thyroid-stimulating antibody (TSAb)-IgG-stimulated cAMP production (thyroid stimulating (TS) index) in porcine thyroid cell (PTC) assay. In the present study the clinical usefulness of the practical method using high PEG concentrations was examined. TS activity using PEG 22.5% precipitated fraction (PF) was significantly higher compared to standard TSAb activity using 12.5% PF from TSAb-positive serum, but the maximum TS activity was observed with PEG 12.5% PF + 4% PEG or PEG 22.5% PF + 2% PEG. In all cases of untreated Graves' patients, TSAb activity determined by PEG 22.5% PF was higher compared to standard TSAb activity using PEG 12. 5% PF from test serum, but the highest TSAb activity was observed by PEG 12.5% PF + 4% PEG without increased cAMP production to normal serum. TSAb was positive in 85% (40/47), 98% (46/47) and 100% (47/47) of untreated Graves' patients by the method of PEG 12.5% PF, PEG 22.5% PF and PEG 12.5% + 4% PEG, respectively. Increased TSAb activity by PEG 12.5% PF + 4% PEG method was also observed even if the standard TSAb activity using PEG 12.5% PF method was negative in the euthyroid states of Graves' patients during antithyroid drug therapy. The stimulatory effect of PEG on TS activity was not found in other thyroidal diseases [thyroiditis chronica (with high serum TSH), thyroid stimulation-blocking antibody (TSBAb)-positive sera (with low serum TSH), adenomatous goiter, subacute thyroiditis, and thyroid cancer]. The stimulatory effect of 5% PEG on TS activity produced directly by small amounts of Graves' serum (50 microl) was also found, although the sensitivity was lower than with PEG-precipitated IgG from 0.2 ml serum. The clinical usefulness of the sensitive TSAb assay using PEG-precipitated IgG or direct serum assay in the presence of high PEG concentrations was demonstrated.

Biological Assay↗
PubMed1999

Clinical significance of a sensitive assay for thyroid-stimulating antibodies in Graves' disease using polyethylene glycol at high concentrations and porcine thyroid cells.

The Inui and Ochi group recently reported that cAMP production by porcine thyroid cells (PTC) was augmented more by polyethylene glycol (PEG) 22.5% precipitated fractions from almost all Graves' sera than those of PEG 12.5%. In the present study, thyroid stimulating immunoglobulin (TSI) activity was determined with PTC and prepared crude Ig fractions precipitated by two different concentrations of PEG (final concentrations 13.5% and 22.5%) from sera obtained from 117 Graves' patients. The activity of TSI determined by the PEG 13.5% assay and activity determined by the PEG 22.5% assay were designated as thyroid-stimulating antibody (TSAb) and sTSAb, respectively. At first we studied 55 TSAb-positive patients with untreated hyperthyroid Graves' disease and classified them according to the TSAb activity-below 500% (group 1) and above 500% (group 2). The positive stimulatory effect, arbitrarily defined as the ratio of sTSAb to TSAb, being more than 1.2, was observed in 85% of patients, and group 1 had a significantly (P<0.025) greater stimulatory effect (34/35, 97.1%) than group 2 (13/20, 65%). Subsequently, in 29 TSAb-negative patients, sTSAb was measured and detected in 26 (89.7%). Finally, sTSAb, TSAb and TBII were compared between patients presenting with recurrent Graves' disease and those with silent thyroiditis after withdrawal of antithyroid drug treatment for Graves' disease. sTSAb was detected in all 14 relapsed patients, but none of the 9 patients with silent thyroiditis had detectable sTSAb. In contrast, TSAb and TBII activities were found in only 7 (50.0%) of the 14 relapsed cases. The present paper demonstrated that the assay with a higher PEG concentration was found to be sensitive, specific and useful for the diagnosis and follow-up of Graves' disease after drug withdrawal, although the underlying mechanism remains unclear.

Adolescent↗
PubMed1999

[Sex differences in subjective well-being and related factors in elderly people in the community aged 75 and over].

Sex differences in factors related to subjective well-being were evaluated in people in their late old age by interviewing individuals aged 75 years and over living in 2 regions of Enzan City, Yamanashi Prefecture. The 17-item revised "Philadelphia Geriatric Center (PGC) Morale Scale" was used for evaluation of subjective well-being. Factors related to family status, employment, health related factors, activities of daily living, and results of physical examinations were each classified into two or more categories, and PGC Morale Scale points were compared among the categories for all subjects and separately for males and females using the Mann-Whitney test and the Kruskal-Wallis test. 1) Although the mean age of males (80.0 +/- 4.4 years) and females (80.4 +/- 4.3 years) was no significantly difference, PGC Morale Scale points were significantly higher in males than in females (p < 0.05), indicating a sex difference in subjective well-being. 2) In elderly females, subjective well-being was related to many factors, and there was a particularly strong relationship between subjective well-being and both health related factors and activities of daily living. 3) In elderly males, the factors related to subjective well-being were fewer than in females, consisting only of "social opportunities", "hobbies", and "grip strength". Since factors related to subjective well-being differ between the sexes, these differences must be taken into account when evaluating subjective QOL of the elderly.

Aged↗
PubMed1999

Disruption of cholecystokinin (CCK)-B receptor gene did not modify bile or pancreatic secretion or pancreatic growth: a study in CCK-B receptor gene knockout mice.

Pancreatic exocrine function and bile secretion were examined in cholecystokinin (CCK)-B receptor gene-targeted mice and compared among different genotypes [i.e., CCK-B receptor gene: (+/+), wild-type; (+/-), heterozygous; and (-/-), homozygous deficient]. The histology and protein concentrations in the pancreas also were examined. Amylase release from the dispersed acini was examined in vitro by using the various doses of CCK-8, carbachol, and secretin. In vivo, the bile and pancreatic juice were collected, and the concentrations of amylase and bile acid were measured in anesthetized mice. The responses to CCK (100 pmol/kg) or acetyl-beta-methylcholine (500 nmol/kg) were examined. In vitro studies showed that the maximal effective concentrations of CCK-8 (10(-l0) M), carbachol (10(-5) M), and secretin (5 x 10(-7) M) were comparable for all genotypes. Fluid, amylase, and bile acid outputs in vivo also were comparable for all genotypes. Pancreatic wet weight and protein concentrations were not significantly different, and no abnormal findings were observed on histologic examination in any genotype. These results indicated that the CCK-B receptor has no role in pancreatic growth, exocrine secretion, or bile secretion in adult mice.

Aging↗
PubMed1998

Increase of thyroid stimulating activity in Graves' immunoglobulin-G by high polyethylene glycol concentrations using porcine thyroid cell assay.

Cyclic adenosine monophosphate (cAMP) production during a 5-hour incubation using porcine thyroid cells (PTC) was stimulated significantly more by polyethylene glycol (PEG) 22.5% precipitated fractions (ppt frs) than by PEG 12.5% ppt frs from almost all Graves' sera. However, the thyrotropin (TSH) binding inhibition (TBI) activities of the PEG 12.5% and 22.5% ppt frs using porcine thyroid membranes were similar, and did not change in the 5-hour incubation. When the PEG 12.5% ppt fr from Graves' serum and the PEG 22.5% ppt fr from normal human serum (NHS) were coincubated, cAMP production was also stimulated as much as by the PEG 22.5% ppt fr from Graves' serum. When purified thyroid stimulating antibody (TSAb)-immunoglobulin G (IgG) and the PEG 22.5% ppt fr from NHS were coincubated, increased cAMP production was also observed, whereas bovine thyrotropin (bTSH) did not produce this effect. When purified TSAb-IgG and PEG solutions were coincubated, maximum increases in cAMP production (approximately 10-fold) with 5% PEG were found, whereas no increase was observed using bTSH. The stimulatory effect of high PEG concentrations on thyroid stimulating activity was observed by TSAb-IgG in salt-free or salt-containing medium (<0.15 mol/L NaCl concentration) but not by either TSAb-IgG conjugated to protein A-sepharose 4B or the inactivated TSAb-IgG by the treatment of 70 degrees C for 10 minutes. No stimulatory action by PEG was found with the thyroid stimulating substances such as GTPgammaS, forskolin, or pituitary adenylate-cyclase activating polypeptide (PACAP). The increased thyroid stimulating activity of Graves (IgG) at high PEG concentrations suggests the existence of some factors influencing the ability of TSAb to stimulate thyroid cells, although the exact mechanism remains to be clarified.

Animals↗
PubMed1998

The effects of the lateral position on cardiopulmonary function during laparoscopic urological surgery.

UNLABELLED: Laparoscopic urological surgery is usually performed transperitoneally with retroperitoneal insufflation of carbon dioxide (CO2) in the lateral position. We studied whether a difference in the side of lateral position affected hemodynamic and pulmonary functions during pneumoperitoneum. Fifteen patients (eight in the right and seven in the left lateral position) undergoing elective laparoscopic urological surgery were studied under general anesthesia. Hemodynamic variables and blood gas data were recorded. Before insufflation, mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) in the right lateral position were higher than those in the left lateral position. Pneumoperitoneum increased MAP, MPAP, CVP, PCWP, and cardiac index but decreased systemic vascular resistance in the right lateral position. Similar changes occurred during pneumoperitoneum in the left lateral position, but the changes were less than those in the right lateral position. The respiratory index (PaO2/PAO2), intrapulmonary shunt, and SpO2 did not change during pneumoperitoneum in either lateral position. Changing the side of the lateral position affected hemodynamic function but did not affect pulmonary oxygenation during pneumoperitoneum. IMPLICATIONS: The right and left lateral positions produced different hemodynamic changes during laparoscopic urological surgery. The increases in preload and cardiac index and the decrease in systemic vascular resistance were greater in the right than in the left lateral position. Respiratory changes were not affected differently between the right and left lateral positions.

Anesthesia, General↗
PubMed1998

Propofol inhibits ketamine-induced c-fos expression in the rat posterior cingulate cortex.

UNLABELLED: Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has psychotomimetic activity. NMDA receptor antagonists cause morphological damage in the posterior cingulate cortex, which may be the brain region responsible for their psychotomimetic effects. Benzodiazepines are effective in preventing these effects through gamma-aminobutyric acid A (GABA(A)) receptor activation. We investigated the effect of propofol, which has both GABAA receptor-activating and NMDA receptor-suppressing activity, on ketamine-induced c-fos expression in the rat posterior cingulate cortex. Propofol or vehicle was continuously infused IV. Fifteen minutes later, 100 mg/kg ketamine or isotonic sodium chloride solution was injected intraperitoneally. Two hours later, brain sections were prepared, and c-fos expression was detected using immunohistochemical methods. Propofol significantly inhibited ketamine-induced c-fos expression in the posterior cingulate cortex. Propofol itself did not induce c-fos expression in this brain region. We conclude that propofol may be able to inhibit ketamine-induced psychotomimetic activity and neuronal damage. IMPLICATIONS: In the present study, we demonstrated that the clinically relevant dose of propofol significantly inhibited ketamine-induced c-fos expression in the rat posterior cingulate cortex. This finding implies that propofol may inhibit ketamine-induced psychotomimetic activity and neuronal damage.

Anesthetics, Dissociative↗