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H Ishihara

Publications and source records attributed to H Ishihara.

At least 163 records · Page 9Linked to original sources
PubMed1998

Type I phosphatidylinositol-4-phosphate 5-kinases synthesize the novel lipids phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 5-phosphate.

Inositol phospholipids regulate a variety of cellular processes including proliferation, survival, vesicular trafficking, and cytoskeletal organization. Recently, two novel phosphoinositides, phosphatidylinositol-3,5-bisphosphate (PtdIns-3,5-P2) and phosphatidylinositol- 5-phosphate (PtdIns-5-P), have been shown to exist in cells. PtdIns-3,5-P2, which is regulated by osmotic stress, appears to be synthesized by phosphorylation of PtdIns-3-P at the D-5 position. No evidence yet exists for how PtdIns-5-P is produced in cells. Understanding the regulation of synthesis of these molecules will be important for identifying their function in cellular signaling. To determine the pathway by which PtdIns-3,5-P2 and Ptd-Ins-5-P might be synthesized, we tested the ability of the recently cloned type I PtdIns-4-P 5-kinases (PIP5Ks) alpha and beta to phosphorylate PtdIns-3-P and PtdIns at the D-5 position of the inositol ring. We found that the type I PIP5Ks phosphorylate PtdIns-3-P to form PtdIns-3,5-P2. The identity of the PtdIns-3,5-P2 product was determined by anion exchange high performance liquid chromatography analysis and periodate treatment. PtdIns-3,4-P2 and PtdIns-3,4,5-P3 were also produced from PtdIns-3-P phosphorylation by both isoforms. When expressed in mammalian cells, PIP5K Ialpha and PIP5K Ibeta differed in their ability to synthesize PtdIns-3,5-P2 relative to PtdIns-3,4-P2. We also found that the type I PIP5Ks phosphorylate PtdIns to produce PtdIns-5-P and phosphorylate PtdIns-3,4-P2 to produce PtdIns-3,4,5-P3. Our findings suggest that type I PIP5Ks synthesize the novel phospholipids PtdIns-3,5-P2 and PtdIns-5-P. The ability of PIP5Ks to produce multiple signaling molecules indicates that they may participate in a variety of cellular processes.

Animals↗
PubMed1998

Antibodies to protease-activated receptor 3 inhibit activation of mouse platelets by thrombin.

Recent studies of mice deficient in the thrombin receptor, protease-activated receptor 1 (PAR1), provided definitive evidence for the existence of a second thrombin receptor in mouse platelets. We recently identified a new thrombin receptor designated protease-activated receptor 3 (PAR3). The mRNA encoding a mouse homologue of PAR3 was highly expressed in mouse splenic megakaryocytes, making it a good candidate for the missing mouse platelet thrombin receptor. We now report that PAR3 protein is expressed on the surface of mouse platelets and that PAR3 antibodies partially inhibit activation of mouse platelets by thrombin but not U46619, a thromboxane receptor agonist. These observations suggest that PAR3 contributes to mouse platelet activation by thrombin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Involvement of heat shock protein 90 in the degradation of mutant insulin receptors by the proteasome.

We previously reported three families with type A insulin-resistant syndrome who had mutations, either Asp1179 or Leu1193, in the kinase domain of the insulin receptor. The extreme insulin resistance of these patients was found to be caused by the decreased number of insulin receptors on the cell surface, due to the intracellular rapid degradation (Imamura, T., Takata, Y., Sasaoka, T., Takada, Y., Morioka, H., Haruta, T., Sawa, T., Iwanishi, M., Yang, G. H., Suzuki, Y., Hamada, J., and Kobayashi, M. (1994) J. Biol. Chem. 269, 31019-31027). In the present study, we first examined whether these mutations caused rapid degradation of unprocessed proreceptors, using the exon 13 deleted mutant insulin receptors (DeltaEx13-IR), which were accumulated in the endoplasmic reticulum as unprocessed proreceptors. The addition of Asp1179 or Leu1193 mutation to DeltaEx13-IR caused accelerated degradation of the unprocessed DeltaEx13-IR in the transfected COS-7 cells. Next, we tested whether these mutant receptors were degraded by the proteasome. Treatment with proteasome inhibitors Z-Leu-Leu-Nva-H (MG-115) or Z-Leu-Leu-Leu-H (MG-132) prevented the accelerated degradation of these mutant receptors, resulting in increased amounts of the mutant receptors in the COS-7 cells. Essentially the same results were obtained in the patient's transformed lymphocytes. Finally, we found that these mutant receptors bound to heat shock protein 90 (Hsp90). To determine whether Hsp90 played an important role in the accelerated receptor degradation, we examined the effect of anti-Hsp90 antibody on the mutant receptor degradation. The microinjection of anti-Hsp90 antibody into cells prevented the accelerated degradation of both Asp1179 and Leu1193 mutant insulin receptors. Taken together, these results suggest that Hsp90 is involved in dislocation of the mutant insulin receptors out of the endoplasmic reticulum into the cytosol, where the mutant receptors are degraded by the proteasome.

Animals↗
PubMed1998

Familial predisposition for lumbar degenerative disc disease. A case-control study.

STUDY DESIGN: A case-control study using magnetic resonance imaging and plain radiography to evaluate whether a family history of lumbar disc herniation is a risk factor for disc degeneration. OBJECTIVES: To evaluate the significance of a family history of operated lumbar disc herniation in the development of lumbar disc degeneration and lumbar disc herniation. SUMMARY OF BACKGROUND DATA: There are only a few epidemiologic studies indicating that a family history of intervertebral disc herniation is a risk factor for juvenile disc herniation. Recently, similarities in degenerative findings of the lumbar spine between identical twins have been reported. METHODS: In the case group, 24 patients who were the immediate relatives of patients who had undergone surgery for disc herniation and who presented or had a history of low back pain and/or unilateral leg pain were included. Control individuals included 72 age- and gender-matched outpatients who reported low back pain and/or leg pain without a family history of operated disc herniation. The incidence, level, and topographic location of disc herniation/diffuse bulge; the incidence and grade of disc degeneration observed on magnetic resonance images; and degenerative changes suggesting disc degeneration observed on plain radiographs were compared between the relatives of patients with disc herniation (cases) and the controls. RESULTS: The incidence of disc degeneration at L4-L5 and L5-S1 in cases (L4-L5, 18/24; L5-S1, 18/24) and controls (L4-L5, 45/72; L5-S1, 43/72) was similarly high. However, the grade of disc degeneration according to magnetic resonance imaging signal intensity on the T2-weighted sagittal image using Schneiderman's four-grade classification was significantly more severe in cases (L4-L5: Grade 1, 6/24; Grade 2, 4/24; Grade 3, 13/ 24; Grade 4, 1/24; L5-S1: Grade 1, 6/24; Grade 2: 3/24, Grade 3: 12/24, Grade 4: 3/24) than in controls (L4-L5: Grade 1, 27/72; Grade 2, 24/72; Grade 3, 20/72; Grade 4, 1/72; P = 0.034; L5-S1: Grade 1, 29/72; Grade 2, 23/72; Grade 3, 13/72; Grade 4, 7/72; P = 0.023; Mann-Whitney U test). The incidence of disc herniation/diffuse bulge at L4-L5 (16/24) and L5-S1 (11/24) in cases was higher than that in controls (L4-L5, 33/72; P = 0.07; L5-S1, 17/ 72; P = 0.04; chi-square test). CONCLUSION: The current study provided evidence that a family history of operated lumbar disc herniation has a significant implication in lumbar degenerative disc disease. There may be a genetic factor in the development of lumbar disc herniation as an expression of disc degeneration.

Adolescent↗
PubMed1998

Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family.

Type I phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinases (PIP5K) catalyze the synthesis of phosphatidylinositol 4, 5-bisphosphate, an essential lipid molecule in various cellular processes. Here, we report the cloning of the third member (PIP5Kgamma) and the characterization of members of the type I PIP5K family. Type I PIP5Kgamma has two alternative splicing forms, migrating at 87 and 90 kDa on SDS-polyacrylamide gel electrophoresis. The amino acid sequence of the central portion of this isoform shows approximately 80% identity with those of the alpha and beta isoforms. Northern blot analysis revealed that the gamma isoform is highly expressed in the brain, lung, and kidneys. Among three isoforms, the beta isoform has the greatest Vmax value for the PtdIns(4)P kinase activity and the gamma isoform is most markedly stimulated by phosphatidic acid. By analyzing deletion mutants of the three isoforms, the minimal kinase core sequence of these isoforms were determined as an approximately 380-amino acid region. In addition, carboxyl-terminal regions of the beta and gamma isoforms were found to confer the greatest Vmax value and the highest phosphatidic acid sensitivity, respectively. It was also discovered that lysine 138 in the putative ATP binding motif of the alpha isoform is essential for the PtdIns(4)P kinase activity. As was the case with the alpha isoform reported previously (Shibasaki, Y., Ishihara, H., Kizuki, N., Asano, T., Oka, Y., Yazaki, Y. (1997) J. Biol. Chem. 272, 7578-7581), overexpression of either the beta or the gamma isoform induced an increase in short actin fibers and a decrease in actin stress fibers in COS7 cells. Surprisingly, a kinase-deficient substitution mutant also induced an abnormal actin polymerization, suggesting a role of PIP5Ks via structural interactions with other molecules.

Amino Acid Sequence↗
PubMed1998

Alternative promoters regulate transcription of the mouse GATA-2 gene.

Transcription factor GATA-2 has been shown to be a key regulator in hematopoietic progenitor cells. To elucidate how the expression of the GATA-2 gene is controlled, we isolated the mouse GATA-2 (mGATA-2) gene. Transcription of mGATA-2 mRNAs was found to initiate from two distinct first exons, both of which encode entirely untranslated regions, while the remaining five exons are shared by each of the two divergent mRNAs. Reverse transcriptase-polymerase chain reaction analysis revealed that GATA-2 mRNA initiated at the upstream first exon (IS) in Sca-1+/c-kit+ hematopoietic progenitor cells, whereas mRNA that initiates at the downstream first exon (IG) is expressed in all tissues and cell lines that express GATA-2. While the structure of the IG exon/promoter shows high similarity to those of the Xenopus and human GATA-2 genes, the IS exon/promoter has not been described previously. When we examined the regulation contributing to IS transcription using transient transfection assays, we found that sequences lying between -79 and -61 are critical for the cell type-specific activity of the IS promoter. DNase I footprinting experiments and electrophoretic mobility shift assays demonstrated the binding of transcription factors to this region. These data indicate that the proximal 80 base pair region of IS promoter is important for the generation of cell type-specific expression of mGATA-2 from the IS exon.

Animals↗
PubMed1998

Significance of sciatic scoliotic list in operated patients with lumbar disc herniation.

STUDY DESIGN: The authors retrospectively reviewed the relation between the location of disc herniation and pre- and postoperative changes in sciatic scoliotic list in 40 patients with surgically confirmed lumbar disc herniation who had sciatic scoliotic list with postoperative recovery. Clinical factors associated with scoliosis also were included. OBJECTIVES: To evaluate the significance and pathomechanism of sciatic scoliotic list. SUMMARY OF BACKGROUND DATA: The proposed causes of lumbar sciatic scoliosis mainly imply an alleviation of nerve root irritation in relation to the anatomic location of disc herniation relative to the nerve root. METHODS: The pre- and postoperative serial Cobb angle between L1 and L5 in anteroposterior lumbar radiographs in the standing position were measured. The relation between the convex side of scoliosis and clinical parameters in terms of the side of symptoms, age, gender, duration of low back pain or leg pain, the angle of a positive straight leg raising test, and the time required for recovery of sciatic scoliosis were investigated. In addition, magnetic resonance imaging also was performed in five recent cases from 40 patients. RESULTS: The average Cobb angle decreased from 10.7 degrees to 2.7 degrees within an average of 7.5 months after surgery. The preoperative Cobb angle of patients with disc herniation medial to the nerve root was significantly higher than that just beneath or lateral to the nerve root. Thirty-two of 40 patients (80.0%) had a lumbar disc herniation at the convex side of scoliosis, irrespective of the transverse location of the herniation. The time required for scoliosis disappearance in disc herniation located lateral to the nerve root tended to be longer than that for other types of disc herniation. Magnetic resonance imaging through the paramedian planes showed enlargement of the intervertebral foramen at the convex side of scoliosis, compared with that at the concave side in five recent cases from the current study. CONCLUSION: These results suggest that sciatic scoliotic list is not a predictive factor of the anatomic location of disc herniation; rather, it is only suggestive of the side of disc herniation. The location of disc herniation may aide in the preoperative estimation of the recovery of the scoliosis.

Adolescent↗
PubMed1998

Repetitive mitochondrial Ca2+ signals synchronize with cytosolic Ca2+ oscillations in the pancreatic beta-cell line, MIN6.

We examined the relationship between cytosolic Ca2+ concentration ([Ca2+]c) and mitochondrial matrix Ca2+ concentration ([Ca2+]m) in the pancreatic beta-cell line, MIN6. [Ca2+]c was monitored in a single or a group (30 cells) of fura-2-loaded MIN6 cells, and [Ca2+]m was measured in a group (1 x 10[6] cells) of MIN6 cells stably transfected with aequorin targeted at the mitochondria. Exogenous ATP (0.25 mmol/l) produced a single transient increase in [Ca2+]c whereas 22 mmol/l KCl produced a sustained plateau increase. ATP and KCl evoked transient increases in [Ca2+]m but with distinct time courses of [Ca2+]m decline: the [Ca2+]m increase induced by ATP decreased more rapidly than that induced by KCl. Nitrendipine (3 micromol/l), a blocker of L-type Ca2+ channels, inhibited both [Ca2+]c and [Ca2+]m signals in response to KCl and tolbutamide, but not those to ATP. Peak levels of [Ca2+]m increase (around 2 micromol/ l) exceeded those of [Ca2+]c increase (around 500 nmol/l). A rise in glucose concentration from 3 to 30 mmol/l induced oscillations of [Ca2+]c that overlay the sustained increases in [Ca2+]c in single cells. An oscillatory increase in [Ca2+]m was similarly observed in response to glucose. Addition of 10 mmol/l 2-ketoisocaproic acid at 20 mmol/l glucose further increased the plateau level of [Ca2+]c and the frequency of [Ca2+]c oscillations, which were correlated with a further increase in [Ca2+]m. In response to pulsatile exposure to KCl, [Ca2+]c and [Ca2+]m increased synchronously. These data suggest that an oscillatory increase in [Ca2+]m in beta cells, the signal which is thought to be necessary for continuous stimulation of mitochondrial metabolism, is produced synchronously with the [Ca2+]c oscillations.

Adenosine Triphosphate↗
PubMed1998

Role of JTT-501, a new insulin sensitiser, in restoring impaired GLUT4 translocation in adipocytes of rats fed a high fat diet.

JTT-501 is an insulin-sensitising compound with an isoxazolidinedione rather than a thiazolidionedione structure. Sprague-Dawley rats fed a high fat diet for 2 weeks were used as an animal model of insulin resistance, and JTT-501 was administered for the final week of the diet. An euglycaemic glucose clamp study showed that the glucose infusion rate (GIR) required to maintain euglycaemia was 57% lower in rats fed a high fat diet than in control rats, and that JTT-501 treatment restored the reduction in GIR produced by the high fat diet. To explain the mechanisms underlying the effects of a high fat diet and JTT-501 treatment, epididymal fat pads were excised and used in the analysis of insulin action. The high fat diet caused: (1) a 58% decrease in insulin receptor substrate-1 (IRS-1) content with a 58% decrease in IRS-1 tyrosine phosphorylation; (2) reductions of 56% and 73% respectively in insulin-induced maximal PI 3-kinase activation in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates; (3) a 46% reduction in the glucose transporter protein, GLUT4 content and, consequently, (4) severely impaired insulin-induced GLUT4 translocation to the plasma membrane and glucose uptake in adipocytes. JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Insulin-stimulated PI 3-kinase activation was also restored in anti-phosphotyrosine and anti-IRS-1 antibody immunoprecipitates. As reflected by these improvements in insulin signalling, JTT-501 treatment improved considerably insulin-induced GLUT4 translocation to the plasma membrane as well as insulin-induced glucose uptake. However, JTT-501 had no effect on the decrease in GLUT4 content produced by the high fat diet. These observations suggest that JTT-501 enhances insulin signalling and may be effective in reducing insulin resistance.

Adipocytes↗
PubMed1998

Overexpression of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase does not correct glucose-stimulated insulin secretion from diabetic GK rat pancreatic islets.

Glucose-stimulated insulin secretion is impaired in GK (Goto-Kakizaki) rats, perhaps because of abnormalities in glucose metabolism in pancreatic islet beta cells. The glycerol phosphate shuttle plays a major role in glucose metabolism by reoxidizing cytosolic NADH generated by glycolysis. In the pancreatic islets of GK rats, the activity of mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mGPDH), the key enzyme of the glycerol phosphate shuttle, is decreased and this abnormality may be responsible, at least in part, for impaired glucose-stimulated insulin secretion. To investigate this possibility, we overexpressed mGPDH in islets isolated from GK rats via recombinant adenovirus-mediated gene transduction, and examined glucose-stimulated insulin secretion. In islets isolated from diabetic GK rats at 8 to 10 weeks of age, glucose-stimulated insulin secretion was severely impaired, and mGPDH activity was decreased to 79 % of that in non-diabetic Wistar rats. When mGPDH was overexpressed in islets from GK rats, enzyme activity and protein content increased 2- and 6-fold, respectively. Basal (3 mmol/l glucose) and glucose-stimulated (20 mmol/l) insulin secretion from the Adex1CAlacZ-infected GK rat islets were, respectively, 4.4 +/- 0.7 and 8.1 +/- 0.7 ng. x islet(-1) x 30 min(-1), and those from mGPDH-overexpressed GK rat islets 4.7 +/- 0.3 and 9.1 +/- 0.8 ng x islet(-1) x 30 min(-1), in contrast to those from the AdexlCAlacZ-infected non-diabetic Wistar rat islets (4.7 +/- 1.6 and 47.6 +/- 11.9 ng x islet(-1) x 30 min(-1)). Thus, glucose-stimulated insulin secretion is severely impaired in GK rats even in the stage when mGPDH activity is modestly decreased, and at this stage, overexpression of mGPDH cannot restore glucose-stimulated insulin secretion. We conclude that decreased mGPDH activity in GK rat islets is not the defect primarily responsible for impaired glucose-stimulated insulin secretion.

Adenoviridae↗
PubMed1998

Mammalian Polycomb group genes are categorized as a new type of early response gene induced by B-cell receptor cross-linking.

Polycomb group (PcG) genes were initially described in Drosophila melanogaster as regulators of the homeobox gene. Four mammalian homologues, mel-18, bmi-1, M33 and rae-28, are analyzed in this study. They not only regulate mammalian homeotic genes by analogy with their Drosophila counterparts, but also have some influence on the growth and differentiation of B lymphocytes. Here we report that these four mammalian PcG genes are rapidly induced after antigen-receptor cross-linking in B cells. Thus we would like to propose that mammalian PcG genes can be categorized as a new type of immediate early gene.

Animals↗
PubMed1998

Detection of capillary protein leakage by glucose and indocyanine green dilutions during the early post-burn period.

Overestimation of the plasma volume determined by the indocyanine green (ICG) dilution method (PV-ICG) may occur after burns, since this dye has the potential of extravasation in the presence of the capillary protein leakage. Assuming that the initial distribution volume of glucose (IDVG) consistently indicates the extracellular fluid volume of highly perfused organs including plasma, overestimation of the PV-ICG can be detected by a higher PV-ICG/IDVG ratio. The present study was designed to test whether a higher PV-ICG/IDVG ratio is observed within 24 h post-burn compared to the subsequent days. Ten severely burned adult patients admitted to the ICU were studied through the 2nd post-burn day. The daily IDVG and PV-ICG were calculated using a one compartment model by simultaneous administration of glucose, 5 g, and ICG, 25 mg. Although the IDVG increased on the 1st post-burn day (p < 0.05), the PV-ICG remained unchanged. The PV-ICG/IDVG ratio within 24 h post-burn was significantly higher than that on the 1st post-burn day (p < 0.01). Results indicate that overestimation of the PV-ICG can occur within 24 h post-burn and suggest that simultaneous measurement of the IDVG and the PV-ICG would help predict the generalized capillary protein leakage after burns.

Adult↗
PubMed1998

mel-18 negatively regulates cell cycle progression upon B cell antigen receptor stimulation through a cascade leading to c-myc/cdc25.

mel-18 is a mammalian Polycomb group gene encoding a transcriptional repressor with tumor suppressive activity. Overexpression of mel-18 in mice results in cell cycle arrest of B cells upon B cell receptor stimulation with downregulation of c-myc. This phenotype is rescued in mel-18/c-myc double-transgenic mice, suggesting that c-myc locates downstream of mel-18. In mel-18 transgenic mice, the downregulation of cyclins D2 and E; CDK4, -6, and -7; and CDC25A causes the impairment in the activities of cyclin-dependent kinases, resulting in hypophosphorylation of the retinoblastoma protein. In contrast, the upregulation of c-Myc, CDC25, and CDC2/CDK2 kinase activities results in the augmentation of B cell proliferation in mel-18-deficient mice. We therefore propose that mel-18 negatively regulates the cell cycle through a c-myc/cdc25 cascade.

Animals↗
PubMed1998

Pharmacokinetics, metabolism and pharmacodynamics of a benzimidazole angiotensin II type 1 receptor antagonist in the beagle dog and cynomologus monkey.

1. The pharmacokinetics and disposition of E4177, an angiotensin II (Ang II) type 1 receptor antagonist, were studied in the beagle dog and cynomologus monkey following intravenous (i.v.) and oral (p.o.) administration. The relationship between the plasma concentrations of E4177 and Ang II receptor blockade were investigated in both species. 2. Single 0.3 mg/kg i.v. doses of E4177 in dog and monkey were eliminated rapidly. The elimination half-lives were 1.9 and 2.0 h, and the systematic plasma clearance values were 9.1 and 12.9 ml/min/kg respectively. 3. The oral bioavailability of single doses of 0.3-3 mg/kg of E4177 was > 60% in both dog and monkey. The absorption by both species was rapid, with peak plasma levels observed within 1 h, and the areas under the concentration versus time curve to infinity were proportional to the dose. 4. The apparent volumes of distribution at the steady-state were 1.0 and 1.2 l/kg in dog and monkey respectively. Tissue penetration was probably limited by the relatively high binding to plasma proteins (approximately 92.0 and 98.6% in the dog and monkey respectively). 5. Faecal excretion was the major elimination pathway for radioactivity (approximately 90% of the dose) in both species after 1 mg/kg p.o. administration of 14C-E4177. Unchanged E4177 was the major radioactive component in the urine and faeces (0-24 h) of both species, accounting for approximately 85% of dose. In monkey, a minor metabolite in excreta and plasma was identified as the phase 1 metabolite M1, which is produced from E4177 by methyl-hydroxylation. M1 was not detected in dog. 6. The unbound plasma concentration versus blockade of the exogenous Ang II-induced vasopressor response was also determined after an i.v. administration of E4177 to dog and monkey. The relationship between the unbound E4177 concentration and the effect was highly significant in both species. The IC50 of the dog and monkey were not significantly different: 2.6 and 2.7 ng/ml respectively.

Administration, Oral↗
PubMed1998

Ratio of indocyanine green and glucose dilutions detects capillary protein leakage following endotoxin injection in dogs.

This study was designed to determine whether endotoxin-induced generalized capillary protein leakage can be detected using the ratio of indocyanine green (ICG) and glucose dilutions. Plasma volume determined by the ICG dilution method (Vd-ICG) and the initial distribution volume of glucose (IDVG) were assessed simultaneously before and after either the administration of lipopolysaccharide (LPS) 0.3 mg kg-1 or equal amounts of isotonic saline in two groups of eight dogs, using a one-compartment model after simultaneous infusions of both ICG 0.5 mg kg-1 and glucose 100 mg kg-1. The IDVG has been shown to indicate the extracellular fluid volume of highly perfused organs including plasma. All post-treatment values decreased compared with the pre-treatment values (P < 0.05), except Vd-ICG in the LPS group, even though the post-treatment total plasma protein concentration of the LPS group decreased significantly compared with the pre-treatment value (P < 0.05). The post-treatment Vd-ICG/IDVG ratio of the saline group remained unchanged compared with that of the pre-treatment, and the post-treatment ratio of the LPS group increased significantly (P < 0.01). It can be concluded that overestimation of the Vd-ICG can occur after endotoxin injection, which can be detected by simultaneous measurements of the Vd-ICG and the IDVG.

Animals↗
PubMed1998

Effects of thiopental on airway calibre in dogs: direct visualization method using a superfine fibreoptic bronchoscope.

Induction of anaesthesia with thiopental sometimes causes bronchospasm. Although the mechanism by which thiopental induces bronchospasm may involve cholinergic stimulation, direct spastic effect and histamine release, the spastic effects of thiopental have not been comprehensively defined. In this study, we have assessed the effect of thiopental on in vivo airway smooth muscle tone using direct visualization method with a superfine fibreoptic bronchoscope as previously reported. Twenty-one mongrel dogs were anaesthetized with pentobarbital (30 mg kg-1) and paralysed with pancuronium (200 micrograms kg-1 h-1). The trachea was intubated with a tube that had a second lumen for insertion of the bronchoscope (od: 2.2 mm) to continuously measure bronchial cross-sectional area. The tip of the bronchoscope was placed between the second and third bronchial bifurcation of the right lung. The dogs were allocated to three groups of seven: group T, A+T, H+T. In group T, thiopental 0 (saline), 0.1, 1.0 and 10 mg kg-1 was given i.v. In group A+T, saline i.v., 5 min later atropine 0.1 mg kg-1 i.v., and 5 min later thiopental 10 mg kg-1 was administered. In group H+T, bronchoconstriction was produced with histamine 10 micrograms kg-1 i.v. followed by infusion at 500 micrograms kg-1 h-1. Thirty minutes later, thiopental 0, 1.0 and 10 mg kg-1 were given. Arterial blood sampling was performed for measurement of plasma catecholamines and histamine. In group T, thiopental significantly reduced bronchial cross-sectional area (maximally by 28.7 (5.6% at 0.5 min after thiopental 10 mg kg-1), which returned to the baseline in 3 min, while any changes in plasma concentrations of catecholamines and histamine were not observed except norepinephrine level at 1 min following thiopental 10 mg kg-1 i.v. Atropine pretreatment completely prevented thiopental-induced bronchospasm in group A+T. In group H+T, thiopental 10 mg kg-1 transiently but significantly decreases bronchial cross-sectional area. Therefore, the present study indicates that the mechanism of thiopental bronchospasm may result from cholinergic nerve stimulation.

Anesthetics, Intravenous↗
PubMed1998

Effect of carbamazepine on pain scores of unipolar depressed patients with chronic pain: a trial of off-on-off-on design.

OBJECTIVE: The purpose of this study was to evaluate the effect of carbamazepine on chronic pain in patients with major depression. DESIGN: Off-on-off-on carbamazepine treatment design. SETTING: Department of Anesthesiology, Hirosaki University Hospital, Japan. PATIENTS: Fifteen patients with a diagnosis of major depression and chronic pain. INTERVENTION: Depressed patients maintained on antidepressants that had failed to help depression or pain were initially placed on 450 mg carbamazepine at 150 mg three times per day. Carbamazepine was then increased until the patients experienced satisfactory relief of pain. This dose was then maintained for 3 weeks. Afterward, the medication was stopped, and a lactose placebo was administered orally three times per day for 3 weeks. Thereafter, carbamazepine was given for 3 additional weeks at the dose that previously produced satisfactory pain relief. OUTCOME MEASURE: Pain scores were assessed four times during the course of the study: before and after the first and the second treatments with carbamazepine, using a visual analog scale in which 0 represents no pain and 10 unbearable pain. The Hamilton Depression scale was used to judge improvement in the symptoms of depression. RESULTS: Carbamazepine produced a statistically significant reduction in the pain scores, from 8.2 +/- 2.3 to 4.0 +/- 1.1 after the first treatment. The pain score significantly increased to 8.0 +/- 1.0 after stopping carbamazepine, but it decreased significantly to 4.1 +/- 1.8 after the second treatment. The Hamilton scores significantly decreased from 27.4 +/- 7.2 to 20.2 +/- 6.1 after the carbamazepine treatment. CONCLUSIONS: These results may indicate that carbamazepine has both an antidepressive and an analgesic action in depressed patients. Thus, carbamazepine may offer an acceptable therapeutic option in depressed patients with chronic pain that is unresponsive to antidepressants. Alternatively, these results may indicate that carbamazepine appears to help depression in this group of pain patients because of its analgesic effect (i.e., helps depression as a result of helping pain or vice versa).

Adult↗