Search PubMed⌕ Search

Biomedical subjects

A Shigematsu

Publications and source records attributed to A Shigematsu.

At least 55 records · Page 3Linked to original sources
PubMed1999

Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro.

UNLABELLED: The production of proinflammatory cytokines, such as tumor necrosis factor (TNF) a, interleukin (IL)-6, and IL-8, increases in patients with sepsis; marked production causes organ failure and septic shock. We previously reported that ketamine suppressed lipopolysaccharide (LPS)-induced TNF-alpha production in mice. However, there are no reports on the effect of ketamine on cytokine production in human whole blood. Therefore, in this study, we investigated the efficacy of ketamine on LPS-induced TNF-alpha, IL-6, and IL-8 production and recombinant human (rh) TNF-a-induced IL-6 and IL-8 production in human whole blood. After adding different doses of ketamine to whole blood, the blood was stimulated with LPS or rhTNF. After incubation, the plasma TNF-alpha activity and IL-6 and IL-8 concentrations were measured using the L929 cell cytotoxic assay or an enzyme-linked immunoassay. Ketamine significantly suppressed LPS-induced TNF-alpha production at concentrations >20 microg/mL. At concentrations >100 microg/mL, ketamine also significantly suppressed both LPS-induced and rhTNF-induced IL-6 and IL-8 production. In this study, we demonstrated that ketamine directly inhibits the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-8 in human whole blood. IMPLICATIONS: We found that ketamine suppressed lipopolysaccharide-induced tumor necrosis factor alpha, interleukin (IL)-6, and IL-8 production and recombinant human tumor necrosis factor-induced IL-6 and IL-8 production in human whole blood. Ketamine directly suppresses proinflammatory cytokine production.

Anesthetics, Dissociative↗
PubMed1999

The mechanism of inhibitory actions of propofol on rat supraoptic neurons.

BACKGROUND: In the perioperative period, plasma osmotic pressure, systemic blood pressure, and blood volume often change dramatically. Arginine vasopressin is a key factor in the regulation of these parameters. This study was performed to evaluate the direct and the mechanism of the actions of propofol on arginine vasopressin release from magnocellular neurosecretory neurons in the rat supraoptic nucleus. METHODS: Somatodendritic arginine vasopressin release from supraoptic nucleus slice preparations was measured by radioimmunoassay. Ionic currents were measured using the whole-cell mode of the patch-clamp technique in supraoptic nucleus slice preparations or in single dissociated supraoptic nucleus neurons of the rat. RESULTS: Propofol at concentrations greater than 10(-5) M inhibited the arginine vasopressin release stimulated by potassium chloride (50 mM). This inhibition by propofol was not reversed by picrotoxin, a gamma-aminobutyric acid(A)(GABA(A)) receptor antagonist, whereas arginine vasopressin release induced by glutamate (10(-3) M) was also inhibited by propofol at a clinically relevant concentration (10(-6) M). The latter effect was reversed by picrotoxin. Propofol evoked Cl- currents at concentrations ranging 10(-6) to 10(-4) M. Propofol (10(-6) M) enhanced the GABA (10(-6) M)-induced current synergistically. Moreover, propofol (10(-6) M) prolonged the time constant of spontaneous GABA-mediated inhibitory postsynaptic currents. Furthermore, propofol (10(-5) M and 10(-4) M) reversibly inhibited voltage-gated Ca2+ currents, whereas it did not affect currents induced by glutamate (10(-3) M). CONCLUSIONS: Propofol inhibits somatodendritic arginine vasopressin release from the supraoptic nucleus, and the enhancement of GABAergic inhibitory synaptic inputs and the inhibition of voltage-gated Ca2+ entry are involved in the inhibition of arginine vasopressin release.

Anesthetics, Intravenous↗
PubMed1999

Carrageenan primes leukocytes to enhance lipopolysaccharide-induced tumor necrosis factor alpha production.

We have previously reported that pretreatment with carrageenan (CAR) enhances lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production in and lethality for mice. Whole blood cultured in vitro was used to show that CAR pretreatment results in about a 200-fold increase in LPS-induced TNF-alpha production. CAR by itself did not induce TNF-alpha production. However, CAR-treated cultured medium sensitized whole blood to make more LPS-induced TNF than did saline-treated cultured medium in vitro. It was also demonstrated that CAR pretreatment increases TNF-alpha mRNA levels of both blood cells and peritoneal exudate cells, but not of bone marrow cells. Immunoelectron microscopic analysis revealed that polymorphonuclear leukocytes and macrophages are TNF-alpha-producing cells in CAR-treated mice. In CAR-treated mice, TNF-alpha was seen early after LPS injection in leukocytes in hepatic sinusoids and on the surfaces of endothelial cells. TNF-alpha was also detected late after LPS injection in hepatocytes which become edematous. These results suggest that CAR primes leukocytes to produce TNF-alpha in response to LPS and that they play an important role in the pathogenesis of liver injury.

Animals↗
PubMed1999

[Prolonged effects of vecuronium in a patient with Crow-Fukase syndrome].

We gave anesthesia to a patient with the Crow-Fukase syndrome. A patient with this syndrome shows polyneuropathy, endocrinological symptoms, skin change, hypertrichosis, organomegaly and osteosclerotic change. We monitored the effects of vecuronium using a neuromuscular blockade monitor. The patient with this syndrome was hypersensitive to vecuronium and its effects lasted longer than usual. It is important to monitor neuromuscular blockade carefully in patients with this syndrome.

Anesthesia, General↗
PubMed1999

[Effects of various lidocaine compounds on cuff pressure of a reinforced tracheal tube].

Effects of various lidocaine compounds on cuff pressure of a tracheal tube were studied. Thirty reinforced tracheal tubes (Mallinckrodt Medical, Ireland) were divided into five groups and the cuffs were treated with normal saline, 2% lidocaine jelly, plain lubricant jelly, 4% lidocaine solution or 8% lidocaine pump spray. The cuff pressures of each tube was measured with 5, 10, 15, and 20 ml of air at the time of 0, 30, 60, 90, and 120 min after the treatment. The cuff pressures with 20 ml of air (P20) were compared among the groups. Thirty min after the treatment on the cuffs, P20 of the tubes with lidocaine spray significantly decreased than that of the control tubes with normal saline. In 2 of 10 tubes on which lidocaine had been sprayed, the cuffs were damaged 90 min after the treatment. Any jelly or solution on the cuffs did not influence the cuff pressure-volume relationship. We conclude that lidocaine pump spray should not be used as a lubricant on the cuff of a reinforced tracheal tube.

Aerosols↗
PubMed1998

[Basic life support skills of the first aid course II/standard first aid course ambulance personnel].

This study was undertaken to evaluate thirteen elements of basic life support skills of the First Aid Course II/Standard First Aid Course (FAC II/SFAC) ambulance personnel and to determine the effects of FAC II/SFAC education and basic life support instructor courses. Ninety-eight FAC II/SFAC ambulance personnel were enrolled in this study. It was found that only half of the personnel possessed the skills required for assessing respiration, mask holding and producing adequate tidal volume by the bag-valve-mask devices at the acceptable levels. Regarding the effect of the time that had passed following FAC II/SFAC education, we did not find any correlation between the time and the levels of skills. However, there was a tendency in which the skills for assessing mental status/respiration and for manual airway control were less adequately possessed by FAC II/SFAC personnel who did not take basic life support instructor courses, particularly those who had completed FAC II/SFAC education more than four years prior to this study. Since airway control and respiratory management play a key role in saving patients in life-threatening conditions, we need to critically reevaluate how the initial FAC II/SFAC education and continuing education programs can best be implemented.

Ambulances↗
PubMed1998

C-type natriuretic peptide inhibits rat mesangial cell proliferation by a phosphorylation-dependent mechanism.

We studied the effects of C-type natriuretic peptide (CNP) on rat cultured mesangial cell proliferation. (1) Exposure to CNP (10 nM-1 microM for 72 h) inhibited [3H]thymidine incorporation into mesangial cells in a concentration-dependent manner. Atrial natriuretic peptide (1 nM-1 microM), a peptide related to CNP, also decreased [3H]thymidine incorporation into these cells in a concentration-dependent manner. (2) Both CNP (10 nM- microM) and atrial natriuretic peptide (10 nM-1 microM) also decreased mesangial cell number. (3) The cyclic GMP analog, 8-bromo-cyclic GMP (100 microM and 1 microM), mimicked the inhibitory effects of CNP and atrial natriuretic peptide on [3H]thymidine incorporation into mesangial cells, whereas inhibitors of protein kinase C, protein kinase A, and protein kinase G reduced the effect of both natriuretic peptides. Moreover, the phosphatase inhibitor, calyculin A, increased [3H]thymidine incorporation into mesangial cells. (4) CNP and atrial natriuretic peptide decreased interleukin-1-, interleukin-6-, platelet derived growth factor-, angiotensin II-induced [3H]thymidine incorporation into mesangial cells. These results suggest that CNP exerts inhibitory effects on mesangial cell proliferation and that this effects depend on protein phosphorylation pathways.

Angiotensin II↗
PubMed1998

Ketamine interacts with the noradrenaline transporter at a site partly overlapping the desipramine binding site.

Effects of the intravenous anaesthetic ketamine on the desipramine-sensitive noradrenaline transporter (NAT) were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NAT (bNAT). Incubation (1-3 h) of adrenal medullary cells with ketamine (10-300 microM) caused an increase in appearance of catecholamines in culture medium. Ketamine (10-1000 microM) inhibited desipramine-sensitive uptake of [3H]noradrenaline (NA) (IC50=97 microM). Saturation analysis showed that ketamine reduced Vmax of [3H]NA uptake without changing Km, indicating a non-competitive inhibition. Other inhibitors of NAT, namely cocaine and desipramine, showed a competitive inhibition of [3H]NA uptake while a derivative of ketamine, phencyclidine, showed a mixed type of inhibition. Ketamine (10-1000 microM) also inhibited the specific binding of [3H]desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [3H]desipramine binding revealed that ketamine increased Kd without altering Bmax, indicating a competitive inhibition. In transfected Xenopus oocytes expressing the bNAT, ketamine attenuated [3H]NA uptake with a kinetic characteristic similar to that of cultured adrenal medullary cells. These findings are compatible with the idea that ketamine non-competitively inhibits the transport of NA by interacting with a site which partly overlaps the desipramine binding site on the NAT.

Adrenal Medulla↗
PubMed1998

Mechanism of initial distribution of blood-borne colon carcinoma cells in the liver.

BACKGROUND/AIMS/METHODS: The distribution characteristics of a human colon carcinoma cell line, KM12-HX cells, were examined. After intraportal vein (i.p.v.) or intravenous (i.v.) injection into rats, almost all the injected tumor cells are distributed to liver or lung, respectively, both after 30 s and 30 min. Our previous kinetic analysis of the fate of tumor cells revealed that the cumulative amount of tumor cells distributed in the liver is a factor determining the degree of metastasis. Thus, we examined the mechanism of initial efficient trapping of tumor cells by the liver in more detail. RESULTS: Thirty minutes after tumor cells were injected into the left ventricle of the heart, the distribution of tumor cells was more restricted in several tissues (kidney, small intestine, large intestine and spleen), as compared with the distribution of microspheres undergoing 100% extraction, indicating that the first-pass extraction of KM12-HX cells is incomplete in these organs. The hepatic first-pass distribution of these tumor cells was unaffected by pretreatment of liposomes, such that the preinjected amount was sufficient to saturate the phagocytotic function of macrophages. Thus, the mechanism of initial distribution of the tumor cells to the liver is different from the mechanism of liposome uptake by macrophages. Considering that the diameter of microvessels in sinusoid and KM12-HX cells is approximately 7 and 12 microm, respectively, it is possible that these tumor cells are trapped physically in hepatic microvessels. In fact, after i.p.v. injection of microspheres 5 microm in diameter, only 20% of the dose was distributed to liver and the rest to other tissues. In contrast, almost 100% of microspheres 10 microm in diameter were distributed to the liver. CONCLUSIONS: These results support the hypothesis that the initial organ distribution of blood-borne tumor cells is determined by mechanical and physical properties of the cells.

Animals↗
PubMed1998

Anesthetic management of a patient with myasthenia gravis during hypothermic cardiopulmonary bypass.

The anesthetic management of a patient with myasthenia gravis (MG) who underwent cardiac surgery with hypothermic cardiopulmonary bypass (CPB) is described. Using total intravenous anesthesia with propofol and a moderate dose fentanyl, the variations of neuromuscular function and serum anti-acetylcholine receptor antibody concentration were examined in relation to hypothermic CPB in the absence of muscle relaxants. The anesthetic technique used may have helped to avoid the risks incidental to muscle relaxants in this patient with MG undergoing hypothermic CPB.

Aged↗
PubMed1998

A novel method for measuring the hepatic first-pass effect and metabolic rate of L-3,4-dihydroxyphenylalanine (DOPA), diazepam and inulin in rat liver.

A method to analyze in vivo metabolites in blood obtained from the hepatic vein after the intraportal injection of a drug was established. This method includes cannulation into the portal vein, hepatic vein and bile duct, followed by TLC-autoradioluminography of a non-extracted sample. Either [14C]diazepam, L-3,4-dihydroxyphenyL[3-(14)C]alanine or [14C]inulin was administered on the day following the surgical operation to avoid the influence of anesthesia. Radioactive concentrations of [14C]DOPA decreased rapidly in the first 1 min, then decreased gradually. The concentrations of [14C]diazepam increased within the first 1 min and then decreased gradually. The concentration of [14C]inulin was approximately 10 times higher than that of [14C]DOPA, and both decreased gradually. These results show that the uptake levels of the drugs to the liver varied depending on the drugs. The metabolites of [14C]diazepam and [14C]DOPA were detected as early as 5 s after administration. These results suggest that the in vivo hepatic first pass effect of drugs in the early period of injection (5 s) can be studied using these techniques.

Animals↗
PubMed1998

Biodistribution and kinetics of holmium-166-chitosan complex (DW-166HC) in rats and mice.

UNLABELLED: The fate of 166Ho-chitosan complex, a radiopharmaceutical drug for cancer therapy, was determined by studying its absorption, distribution and excretion in rats and mice. METHODS: Holmium-166-chitosan complex [0.75 mg of Ho(NO3)3 x 5H2O and 1 mg chitosan/ head] was administered intrahepatically to male rats. Radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution in tissues were examined. To determine the effects of chitosan in 166Ho-chitosan complex, 166Ho alone [0.75 mg of Ho(NO3)3 x 5H2O/head] was intrahepatically administered to male rats, and radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution were examined. In B16 melanoma-transplanted nude mice, radioactive distribution after intratumoral administration of 166Ho-chitosan complex [0.075 mg of Ho(NO3)3 x 5H2O and 0.10 mg chitosan/head] was investigated also. RESULTS: After administration of 166Ho-chitosan complex, the radioactive concentrations in blood were low, and cumulative urinary and fecal excretions over a period of 0-72 hr were 0.53% and 0.54%, respectively. The radioactive concentrations in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administration site, and only slight radioactivity was detected from the liver, spleen, lungs and bones. On the other hand, results of intrahepatic administration of 166Ho alone showed high radioactive concentrations in the blood, and the whole-body autoradiographs showed that the administered radioactivity was distributed in many organs and tissues. These results strongly suggest that 166Ho is retained at the administration site only when it forms a chelate complex with chitosan. Autoradiographs after intratumoral administration of 166Ho-chitosan complex showed that radioactivity was localized at the site of administration without distribution to the other organs and tissues. CONCLUSION: Administered 166Ho-chitosan complex is retained at the administration site after either intrahepatic or intratumoral administration to rats or tumor-transplanted nude mice.

Animals↗
PubMed1997

Inhibitory effect of the intravenous anesthetic, ketamine, on rat mesangial cell proliferation.

We studied the effects of ketamine and propofol on rat cultured mesangial cell (MC) proliferation. The 72-h exposure to ketamine (1-100 microM) inhibited [3H]thymidine incorporation into the MC in a concentration-dependent manner. Propofol, however, was not effective at inhibition of MC proliferation at doses from 1 to 100 microM. Ketamine also decreased the cell number at clinically relevant concentrations and increased adenosine 3',5'-cyclic monophosphate (cAMP) levels in MC. We also studied the effects of ketamine on cytokine-induced [3H]thymidine incorporation into the cells. Ketamine decreased the tumor necrosis factor-alpha (TNF-alpha)-, interleukin 1 (IL-1)-, and interleukin 6 (IL-6)-induced [3H]thymidine incorporation into the cells. It also decreased angiotensin II (Ag II)-induced [3H]thymidine incorporation. These results suggest that ketamine has inhibitory effects on MC proliferation, but that propofol does not. Because ketamine inhibits TNF-alpha-, IL-1-, and IL-6-induced MC proliferation, it may be useful in suppressing the cell growth clinically.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Contribution of neutrophils to lipopolysaccharide-induced tumor necrosis factor production and mortality in a carrageenan-pretreated mouse model.

Carrageenan (CAR) pretreatment primes mice for lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in sera and increases their mortality rate. To study the contribution of neutrophils in this model, blood neutrophil count was regulated with cyclophosphamide. After LPS challenge, both serum TNF-alpha activity and mortality risk ratio were significantly higher in neutrophilic mice, but significantly lower in neutropenic mice. In vitro, CAR treatment primed for TNF-alpha production of blood neutrophils, but conversely, that of monocytes was suppressed. We suggest that neutrophils are the major cells to produce TNF-alpha and to determine mouse mortality after LPS challenge in the mouse CAR model.

Animals↗