Biomedical subjects

T Furukawa

Publications and source records attributed to T Furukawa.

At least 19 recordsLinked to original sources

PubMed2006

Mismatch of minor histocompatibility antigen contributes to a graft-versus-leukemia effect rather than to acute GVHD, resulting in long-term survival after HLA-identical stem cell transplantation in Japan.

We determined the alleles of five polymorphic molecules including HA-1 and four adhesion molecules for 106 patients transplanted with HLA-identical stem cell grafts and investigated the association of mismatches as correlates of relapse and graft-versus-host disease (GVHD). All 106 recipients underwent stem cell transplantation (SCT) after myeloablative conditioning between 1985 and 2002. Risk status of disease at SCT was standard (n=63) and high (n=42). After SCT, 36, 49 and 33 developed acute GVHD, chronic GVHD and relapsed, respectively. Our patients relapsed at rates of 16.7 and 38.6% with one or more and without incompatibilities (P=0.013). The relapse rates of patients with CD62L, CD31 codon 563, CD31 codon 125, HA-1 and CD49b incompatibilities were 5.9, 11.8, 15.4, 16.0 and 33.3%, respectively. The frequency of acute GVHD did not differ regardless of incompatibilities. In standard-risk group, the accumulated relapse rates of 19 and 44 patients with and without minor histocompatibility antigen incompatibility were 22% and unexpectedly 66%, respectively (P=0.02). The probability of 12-year survival was 88% in the former and 66% in the latter patients (P=0.03). Our data suggest that incompatibility of CD62L, CD31 codon 563 and CD31 codon 125 contributes to a graft-versus-leukemia effect rather than to GVHD, resulting in prolonged survival after HLA-identical SCT.

Acute Disease↗

PubMed2006

Multicentre prospective study of perinatal depression in Japan: incidence and correlates of antenatal and postnatal depression.

A multicentre study on the epidemiology of perinatal depression was conducted among Japanese women expecting the first baby (N = 290). The incidence rate of the onset of the DSM-III-R Major Depressive Episode during pregnancy (antenatal depression) and within 3 months after delivery (postnatal depression) were 5.6% and 5.0%, respectively. Women with antenatal depression were characterised by young age and negative attitude towards the current pregnancy, whereas women with postnatal depression were characterised by poor accommodation, dissatisfaction with sex of the newborn baby and with the emotional undermining. Antenatal depression was a major risk factor for postnatal depression.

Adult↗

PubMed2006

AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer.

DUSP6/MKP-3, a specific inhibitor of MAPK1/ERK2, frequently loses its expression in primary pancreatic cancer tissues. This evidence suggests that constitutive activation of MAPK1 synergistically induced by frequent mutation of KRAS2 and the loss of function of DUSP6 plays key roles in pancreatic carcinogenesis and progression. By profiling of gene expressions associated with downregulation of MAPK1 induced by exogenous overexpression of DUSP6 in pancreatic cancer cells, we found that AURKA/STK15, the gene encoding Aurora-A kinase, which plays key roles in cellular mitosis, was among the downregulated genes along with its related genes, which included AURKB, TPX2 and CENPA. An association of expression and promoter activity of AURKA with MAPK activity was verified. Knockdown of ETS2 resulted in a reduction of AURKA expression. These results indicate that AURKA is a direct target of the MAPK pathway and that its overexpression in pancreatic cancer is induced by hyperactivation of the pathway, at least via ETS2.

Aurora Kinase A↗

PubMed2006

Measurement of a long electronic spin relaxation time of cesium atoms in superfluid helium.

The longitudinal electronic spin relaxation time of Cs atoms optically polarized in superfluid helium (He II, 1.5 K) has been measured with special care to cope with a serious decrease in the number of Cs atoms in the observation region. This decrease, mainly caused by helium convection in introducing the atoms into He II by laser sputtering, was significantly reduced using a new atom implantation method. Combined with a careful correction for the number of atoms, we have determined the relaxation time to be 2.24(19) s or longer, roughly twice as long as that in solid He.

Journal Article↗

PubMed2006

Cloning, functional expression and promoter analysis of xylanase III gene from Trichoderma reesei.

In this study, the xyn3 gene from the filamentous mesophilic fungus Trichoderma reesei (Hypocrea jecorina) PC-3-7 was cloned and sequenced. Analysis of the deduced amino acid sequence of XYN III revealed considerable homology with xylanases belonging to glycoside hydrolase family 10. These results show that XYN III is distinguishable from XYN I and XYN II, two other T. reesei xylanases that belong to the glycosidase family 11. When xyn3 was expressed in Escherichia coli, significant activity was observed in the cell-free extract, and higher activity (13.2 U/ml medium) was recovered from the inclusion bodies in the cell debris. The sequence of the 5'-upstream region of the gene in the parent strain QM9414 is identical to that of PC-3-7, although the expression level of xyn3 in PC-3-7 has been reported to be at least 1,000 times greater than in QM9414. These results suggest that xyn3 expression in T. reesei QM9414 is silenced. The consensus sequences for ACEI, ACEII, CREI, and the Hap2/3/5 protein complex are all present in the upstream region of xyn3. Deletion analysis of the upstream region revealed that two regions containing consensus sequences for the known regulatory elements play important roles for xyn3 expression.

Amino Acid Sequence↗

PubMed2006

PTOV1: a novel testosterone-induced atherogenic gene in human aorta.

There are gender differences in the development of atherosclerosis, possibly owing to differences in sex steroid hormone action and/or metabolism. One of the atherogenic effects of testosterone is thought to be androgen receptor (AR)-mediated vascular smooth muscle cell (VSMC) proliferation. However, the detailed mechanism of this effect, particularly the identity of the genes associated with VSMC proliferation, remains largely unknown. Therefore, we first employed microarray analysis and, subsequently, quantitative RT-PCR to analyse RNA expression in AR-positive human VSMCs treated with testosterone in order to detect testosterone-induced genes associated with cell proliferation. We further examined whether the genes identified were involved in cell proliferation using small interfering RNA (siRNA) transfection. Expression of the gene products was then evaluated in human aorta with various degrees of atherosclerosis in order to evaluate the clinical relevance of the findings. Both microarray and quantitative RT-PCR analyses demonstrated marked induction of the human prostate overexpressed protein 1 (PTOV1) gene by testosterone in the cell lines: this gene was recently identified as a novel androgen-induced gene involved in prostate tumour cell proliferation. Inhibition of PTOV1 by transfection of its corresponding siRNA suppressed testosterone-induced cell proliferation. In human aorta, PTOV1 immunoreactivity in the nuclei of neointimal VSMCs was abundantly detected in male aorta with mild atherosclerotic changes compared with female aorta or male aorta with severe atherosclerotic changes. These findings indicate that the PTOV1 gene is androgen-responsive in VSMCs and that it may play an important role in androgen-related atherogenesis in the human aorta, particularly early atherosclerosis in the male aorta, through regulating proliferation of neointimal VSMCs.

Androgen Antagonists↗

PubMed2006

Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.

BACKGROUND: In order to establish efficient gammadelta T-cell based tumor immunotherapy, we explored a method to enhance the cytotoxicity of gammadelta T cells against leukemia cells by stimulating gammadelta T cells with type I IFN. METHODS: Gammadelta T cells were expanded from normal PBMC by culturing with zoledronate and a low concentration of IL-2 for 2 weeks. For the activation of gammadelta T cells, gammadelta T cells were cultured with type I IFN (HLBI, IFN-alpha2b and IFN-beta) for 1-3 days. The cytotoxicity of HLBI-activated gammadelta T cells against leukemia cell lines and fresh leukemia cells was evaluated by 51Cr-release assay. RESULTS: Gammadelta T cells, which were expanded and purified with magnetic beads using an anti-gammadelta TCR MAb, were demonstrated to be cytotoxic against leukemia cell lines of both lymphoid and myeloid origin and fresh myeloid leukemia cells. By culturing expanded gammadelta T cells with type I IFN, the expression of the activation marker CD69 was increased and the cytometric bead array showed an elevated production of IFN-gamma by gammadelta T cells. In addition, the cytotoxicity of gammadelta T cells against leukemia cells was definitely enhanced by culturing gammadelta T cells with HLBI. DISCUSSION: The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gammadelta T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated gammadelta T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma.

Antigens, CD↗

PubMed2005

Fluoxetine versus other types of pharmacotherapy for depression.

BACKGROUND: Depression is common in primary care and it is associated with marked personal, social and economic morbidity, and creates significant demands on service providers in terms of workload. Treatment is predominantly pharmaceutical or psychological. Fluoxetine, the first of a group of antidepressant (AD) agents known as selective serotonin reuptake inhibitors (SSRIs), has been studied in many randomised controlled trials (RCTs) in comparison with tricyclic (TCA), heterocyclic and related ADs, and other SSRIs. These comparative studies provided contrasting findings. In addition, systematic reviews of RCTs have always considered the SSRIs as a group, and evidence applicable to this group of drugs might not be applicable to fluoxetine alone. The present systematic review assessed the efficacy and tolerability profile of fluoxetine in comparison with TCAs, SSRIs and newer agents. OBJECTIVES: To determine the efficacy of fluoxetine, compared with other ADs, in alleviating the acute symptoms of depression, and to review its acceptability. SEARCH STRATEGY: Relevant studies were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (1966-2004) and Embase (1974-2004). Non-English language articles were included. SELECTION CRITERIA: Only RCTs were included. For trials which have a crossover design only results from the first randomisation period were considered. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers using a standard form. Responders to treatment were calculated on an intention-to-treat basis: drop-outs were always included in this analysis. When data on drop-outs were carried forward and included in the efficacy evaluation, they were analysed according to the primary studies; when dropouts were excluded from any assessment in the primary studies, they were considered as treatment failures. Scores from continuous outcomes were analysed including patients with a final assessment or with the last observation carried forward. Tolerability data were analysed by calculating the proportion of patients who failed to complete the study and who experienced adverse reactions out of the total number of randomised patients. The primary analyses used a fixed effects approach, and presented Peto Odds Ratio (PetoOR) and Standardised Mean Difference (SMD). MAIN RESULTS: On a dichotomous outcome fluoxetine was less effective than dothiepin (PetoOR: 2.09, 95% CI 1.08 to 4.05), sertraline (PetoOR: 1.40, 95% CI 1.11 to 1.76), mirtazapine (PetoOR: 1.64, 95% CI 1.01 to 2.65) and venlafaxine (Peto OR: 1.40, 95% CI 1.15 to 1.70). On a continuous outcome, fluoxetine was more effective than ABT-200 (Standardised Mean Difference (SMD) random effects: - 1.85, 95% CI - 2.25 to - 1.45) and milnacipran (SMD random effects: - 0.38, 95% CI - 0.71 to - 0.06); conversely, it was less effective than venlafaxine (SMD random effect: 0.11, 95% CI 0.00 to 0.23), however these figures were of borderline statistical significance. Fluoxetine was better tolerated than TCAs considered as a group (PetoOR: 0.78, 95% CI 0.68 to 0.89), and was better tolerated in comparison with individual ADs, in particular than amitriptyline (PetoOR: 0.64, 95% CI 0.47 to 0.85) and imipramine (PetoOR: 0.79, 95% CI 0.63 to 0.99), and among newer ADs than ABT-200 (PetoOR: 0.21, 95% CI 0.10 to 0.41), pramipexole (PetoOR: 0.20, 95% CI 0.08 to 0.47) and reboxetine (PetoOR: 0.61, 95% CI 0.40 to 0.94). AUTHORS' CONCLUSIONS: There are statistically significant differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain, and no definitive implications for clinical practice can be drawn. From a clinical point of view the analysis of antidepressants' safety profile (adverse effect and suicide risk) remains of crucial importance and more reliable data about these outcomes are needed. Waiting for more robust evidence, treatment decisions should be based on considerations of clinical history, drug toxicity, patient acceptability, and cost. We need for large, pragmatic trials, enrolling heterogeneous populations of patients with depression to generate clinically relevant information on the benefits and harms of competitive pharmacological options. A meta-analysis of individual patient data from the randomised trials is clearly necessary.

Antidepressive Agents↗

PubMed2005

Very close relationship of the chloroplast genomes among Saccharum species.

We recently determined the complete sequence of the sugarcane chloroplast genome. Here, we have used the information for a comprehensive phylogenetic analysis of the genus Saccharum, using all six species (13 accessions). The polymorphisms between sugarcane and maize in 26 chloroplast genome regions were used for the analysis. In 18 of the 26 regions (a total of 5,381 bp), we found 41 mutations involving 17 substitutions, three inversions, six insertion/deletion mutations, and 15 simple sequence repeat length polymorphisms. Based on these results, we calculated a phylogenetic tree of the genus Saccharum, in which all six species are clearly separated. By the analysis, (1) S. sinense and S. barberi, which have identical sequences, belong to the same clade, whereas the other four species, S. officinarum, S. robustum, S. edule, and S. spontaneum, form an independent clade; (2) S. spontaneum has a paraphyletic relationship with the other five species; and (3) no or very low intraspecific variation was observed in S. officinarum, S. robustum, S. sinense, S. barberi, and S. edule, whereas higher intraspecific variation was observed in S. spontaneum. Based on the number of nucleotide substitutions, the divergence time between S. officinarum and S. spontaneum, and between S. officinarum and maize were calculated to be about 730-780 thousand years ago and about 5.9 million years ago, respectively. These results suggest that the cytoplasm of Saccharum species are very closely related.

Base Sequence↗

PubMed2005

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease.

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.

Adolescent↗

PubMed2005

Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder.

Psychostimulant use disorder and schizophrenia have a substantial genetic basis. Evidence from human and animal studies on the involvement of the gamma-aminobutyric acid (GABA) system in methamphetamine (METH) use disorder and schizophrenia is mounting. As we tested for the association of the human GABA(A) receptor gamma 2 subunit gene (GABRG2) with each diagnostic group, we used a case-control design with a set of 178 subjects with METH use disorder, 288 schizophrenics and 288 controls. First, we screened 96 controls and identified six SNPs in GABRG2, three of whom we newly reported. Next, we selected two SNPs, 315C>T and 1128+99C>A, as representatives of the linkage disequilibrium blocks for further case-control association analysis. Although no associations were found in either allelic or genotypic frequencies, we detected a haplotypic association in GABRG2 with METH use disorder, but not with schizophrenia. This finding partly replicates a recent case-control study of GABRG2 in METH use disorder, and thus indicates that GABRG2 may be one of the susceptibility genes of METH use disorder.

Adolescent↗

PubMed2005

Effect of prostaglandin E2, lipopolysaccharide, IFN-gamma and cytokines on the generation and function of fast-DC.

BACKGROUND: Recent reports have described a new strategy for differentiation and maturation of monocyte-derived DC within only 48 h of in vitro culture (fast-DC). We compared the ability of various maturation stimuli with the generation of Ag-specific T-cell responses and generation of functional fast-DC. METHODS: CD14+ cells were treated with GM-CSF and IL-4 for 1 day to generate immature DC, and were then matured with either inflammatory cytokines or a combination of lipopolysaccharide (LPS) and INF-gamma. Mature DC were then used to study the effect of prostaglandin E2 (PGE2) on the stimulatory function of fast-DC. RESULTS: fast-DC were CD14- and expressed mature DC surface markers, and maintained this phenotype after withdrawing the cytokine from culture. Treatment of fast-DC with a combination of LPS and INF-gamma promoted the maturation of highly uniform fast-DC. The T-cell proliferative response to DC was enhanced by inclusion of PGE2 in the MCM-mimic (TNF-a, IL-1 a, IL-6, PGE2) cocktail. DISCUSSION: fast-DC are very effective; they not only reduce the labor, cost and time required for in vitro DC development, but may also represent a model more closely resembling DC differentiation from monocytes in vivo.

Antineoplastic Agents↗

PubMed2005

A novel exopolysaccharide from a clinical isolate of Prevotella nigrescens: purification, chemical characterization and possible role in modifying human leukocyte phagocytosis.

Prevotella nigrescens, a gram-negative black-pigmented anaerobic rod, has frequently been isolated from periodontitis and periapical periodontitis lesions. We have isolated an exopolysaccharide-producing P. nigrescens, strain 22, from a chronic periodontitis lesion. The purpose of this study was to determine the chemical composition and function of the exopolysaccharide associated with this clinical isolate. The chemical composition and structure of the purified exopolysaccharide from strain 22 were determined by high performance liquid chromatography and methylation analysis. To define the biological function of this exopolysaccharide, a chemically induced exopolysaccharide nonproducing mutant, strain 328, which was derived from strain 22, was established. The biological effects of exopolysaccharide were determined by comparing the ability of strain 22, strain 328 or heat-killed strain 22 to form abscesses in mice and to interfere with the phagocytic activity of peripheral blood polymorphonuclear leukocytes. Chemical analysis showed that isolated exopolysaccharide consisted of mannose (521.6 microg/mg), glucose (25.6 microg/mg), fructose (65.8 microg/mg), galactose (12.5 microg/mg), arabinose (6.2 microg/mg), xylose (3.2 microg/mg), rhamnose (6.1 microg/mg), and ribose (0.6 microg/mg). Methylation analysis of exopolysaccharide indicated that the linkages of mannose were primarily (1-->2, 1-->6) (1-->2) (1-->6), and (1-->3). Strain 22 and, to a lesser extent, its heat-killed counterpart induced greater abscess formation in mice than strain 328, even though the enzymatic profile of strain 22 was similar to that of strain 328. The ability of strain 328 to induce abscess formation was restored by adding the purified exopolysaccharide isolated from strain 22 to the cell suspension of strain 328. Exopolysaccharide alone failed to induce abscess formation in mice. Further, strain 328 but not the untreated or heat-killed strain 22, was phagocytosed by polymorphonuclear leukocytes both in the presence and in the absence of opsonic factors. The results suggest that these polysaccharides isolated from strain 22, which primarily consisted of mannose, may play a key role in the development of the chronic inflammatory lesion from which this strain was isolated.

Abscess↗

PubMed2005

[The relationship between supraventricular arrhythmia after coronary artery bypass grafting and autonomic nerve system].

We evaluated the relationship between supraventricular arrhythmia after coronary artery bypass grafting (CABG) and autonomic nerve system. Holter electrocardiogram was recorded in 57 postoperative patients. The heart rate variability was analyzed in 25 premature atrial contraction (PAC) cases and 4 atrial fibrillation (AF) cases. Sixty minutes just before the onset of PAC/AF were devided into 12 equal parts, and NN 50, RMSSD, HF, LF/HF were measured respectively. NN 50, RMSSD and HF were each used as an indicator to show the parasympathetic nerve (PSN) activity, and LF/HF as an indicator to show the sympathetic nerve (SN) activity. The mean value of the former 6 parts was compared to that of the latter 6 parts. As for 25 PAC cases, PAC occurred under the dominance of PSN in 30% of the cases, under the dominance of SN in 10% of the cases and under the balanced condition of both nerves in 60% of the cases. As for 4 AF cases, AF occurred under the parasympathetic condition in 3 cases and under the sympathetic condition in 1 case. These results show that supraventricular arrhythmia after CABG is associated with PSN system.

Atrial Fibrillation↗

PubMed2004

Significant effects of diacylglycerol on body fat and lipid metabolism in patients on hemodialysis.

AIMS: The long-term effects of dietary diacylglycerol (DAG) on body fat and lipid metabolism were studied in patients undergoing hemodialysis (HD). METHODS: Ten patients (seven males, three females) ranging in age from 40 to 64 years were enrolled. During the test period, 9.8 g of DAG was ingested per day for 3 months. RESULTS: Body mass index did not change throughout the study. The abdominal fat area measured by CT scan decreased significantly at 3 months, and increased significantly 3 months after completion of the DAG ingestion period. The serum composition of very low-density lipoprotein (VLDL) decreased significantly at 3 months and high-density lipoprotein (HDL) increased significantly at 3 months; these were determined using polyacrylamide gel electrophoresis. Serum lipoprotein (a) decreased significantly at 3 months. CONCLUSIONS: Our study showed that 3-month ingestion of DAG reduced the amount of abdominal fat and improved serum lipid profiles in free-living HD patients.

Abdomen↗

PubMed2004

High-dose cytosine arabinoside and etoposide with total body irradiation as a preparatory regimen for allogeneic hematopoietic stem-cell transplantation in patients with acute lymphoblastic leukemia.

One approach to improving the outcome of allogeneic hematopoietic stem-cell transplantation for acute lymphoblastic leukemia (ALL) is to intensify the pretransplant conditioning regimen without increasing toxicity. We used an intensified conditioning regimen consisting of high-dose cytosine arabinoside (3 g/m(2) twice daily i.v. for 3 consecutive days, total six doses), high-dose etoposide (1 g/m(2) once daily i.v. during the first 2 days) and total body irradiation (TBI) (HDACE-TBI) in ALL patients. We retrospectively analyzed 21 patients treated with HDACE-TBI, of whom 18 were in complete remission (CR) and three were in non-CR at transplantation. Although gastrointestinal toxicities were common, critical regimen-related toxicities were not seen in any patients. One patient demonstrated veno-occlusive disease, which could be controlled conservatively. The disease-free survival rate of 18 patients in CR at transplantation was 61%. These results demonstrate that the HDACE-TBI combination regimen is a feasible alternative to other preparatory regimens and does not increase the regimen-related toxicity.

Adolescent↗

PubMed2004

Effect of graft-versus-host disease on the outcome of bone marrow transplantation from an HLA-identical sibling donor using GVHD prophylaxis with cyclosporin A and methotrexate.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.

Adult↗

PubMed2004

Effect of contrast media on vascular smooth muscle cells.

PURPOSE: In order to alleviate the adverse effects of contrast media (CMs) on the vascular system, the role of Ca2+ in the viability of vascular smooth muscle cells (VSMCs) was investigated. MATERIAL AND METHODS: VSMCs were obtained from swine thoracic aorta. The number of VSMCs was counted under a microscope using the trypan blue dye-exclusion method 24 h after culture in RPMI containing physiological saline (SAL) as control, iothalamate (IOT), or iohexol (IOH) at 10% by volume with CaCl2 added at 0 to 2.0 mmol/l. Free Ca2+ in the above media was measured using an ion-selective electrode. RESULTS: Free Ca2+ was 0.4 to 1.5 mmol/l with ionic IOT and 0.4 to 1.8 mmol/l with non-ionic IOH as well as with control. The ratio of viable cells grown in the presence of CMs to those grown in the control was optimal at approximately 0.60 near 1 mmol/l Ca2+ and decreased markedly to 0.00 at 1.5 mmol/l Ca2+ in the presence of IOT and to 0.39 at 1.8 mmol/l Ca2+ in the presence of IOH, while the ratios decreased gradually to 0.28 in the presence of IOT and 0.53 in the presence of IOH at 0.4 mmol/l Ca2+. CONCLUSION: Ionic IOT is more cytotoxic to VSMCs than non-ionic IOH. However, the cytotoxicity was minimal and similar between both CMs at 1 mmol/l Ca2+ in accordance with the sodium-calcium balance.

Animals↗