Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 37 records · Page 2Linked to original sources

PubMed2006

Clinical effects of apple polyphenols on persistent allergic rhinitis: A randomized double-blind placebo-controlled parallel arm study.

BACKGROUND: We often encounter persistent allergic rhinitis due to house dust mites in the practice of otolaryngology, and its prevalence in Japan is high (18.7%). Persistent allergic rhinitis is usually treated with antihistamines and local steroids, but they often cause adverse effects such as sedation and drowsiness. Polyphenols derived from apples have been reported to suppress histamine release from rat cells, reduce auricular swelling in allergic mice, and alleviate skin inflammation in atopic patients. These effects suggest that apple polyphenols are effective for the treatment of various allergic disorders, but the results of their clinical use have not been reported. OBJECTIVE: To assess the effect of drinks containing apple polyphenols on clinical symptoms of persistent allergic rhinitis. METHODS: Thirty-three patients aged 15 to 65 years with moderate or severe persistent allergic rhinitis in whom the symptoms persisted for 3 years or longer were treated without apple polyphenols (control group), with a low dose of apple polyphenols, or with a high dose of apple polyphenols, and changes in the clinical symptoms were examined. RESULTS: Significant improvements were observed in sneezing attacks (P<.05) and nasal discharge (P<.01) in the high-dose group and in sneezing attacks (P<.05) in the low-dose group. Compared with the control group, an improvement was observed in sneezing attacks and nasal discharge in many patients of the polyphenol-treated groups. In terms of intranasal findings, a significant improvement was observed in swelling of the nasal turbinate in the low-dose group (P<.05). The percentage of patients who showed an improvement in swelling of the nasal turbinate was higher in the polyphenol-treated groups. CONCLUSIONS: We conclude that apple polyphenols are effective in alleviating symptoms of persistent allergic rhinitis.

Adult↗

PubMed2006

Expression and mutation of SMAD4 in poorly differentiated carcinoma and signet-ring cell carcinoma of the colorectum.

Poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig) are rare but highly malignant types of colorectal cancer. To explore their genetic backgrounds we investigated TGF-beta type II receptor (TGF-beta RII) and SMAD4 in the TGF-beta signaling pathway, and to identify their mutator phenotype we examined microsatellite instability (MSI) status. Loss of SMAD4 expression was significantly more frequent in Por (12 of 38; 31%) and Sig (4 of 5; 80%) tumors than in well (Well) and moderately differentiated (Mod) carcinomas (p = 0.04, 0.003, respectively). Mutation of the SMAD4 gene was detected in 2 of 26 Por tumors. MSI was positive in 14 of the 38 Por tumors and in 1 of the 5 Sig tumors, but in none of the Well or Mod tumors examined. We also found mutation of TGF-beta RII, a putative target of MSI, in 10 of 35 Por tumors (28.6%), but in none of 3 Sig tumors. As a whole, about 50% of the Por tumors and 80% of the Sig tumors showed abnormalities of either TGF-beta RII or SMAD4 expression. This suggests that disruption of the TGF-beta signaling pathway may play a central role in the pathogenesis of Por and Sig tumors of the colorectum.

Adenocarcinoma↗

PubMed2005

Role of nociceptin and opioid receptor like 1 on entrainment function in the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus of the hypothalamus is the master circadian clock in mammals. Phase shifts in circadian locomotor activity occur when an animal is exposed to light during the subjective night. An endogenous ligand of opioid receptor like 1, nociceptin is reported to inhibit light-induced phase shifts in locomotor activity rhythm. However, little is known about the role of opioid receptor like 1 receptors in the entrainment. Therefore, we investigated the involvement opioid receptor like 1 and its endogenous ligand, intnociceptin, in the suprachiasmatic nucleus and in the entrainment of circadian rhythms in rats. In an in vitro experiment, glutamate (1 microM) -induced phase delay of suprachiasmatic nucleus neuronal activity rhythms was inhibited by nociceptin during the early subjective night. An opioid receptor like 1 antagonist, compound B (10 microM), induced a phase delay, and this effect was blocked by nociceptin (10 microM). Moreover, compound B (10 microM) potentiated the glutamate (1 microM) -induced phase delay. Fos expression in the suprachiasmatic nucleus of rats induced by photic stimulation (50 lux, 30 min) during the early subjective night was inhibited by treatment with nociceptin (0.5-10 nM, i.c.v.). The effect of nociceptin (10nM, i.c.v.) was blocked by pretreatment with compound B (30 mg/kg, i.p). In an in vivo experiment, nociceptin significantly inhibited a light-induced (300 lux, 1 h) phase delay of locomotor activity rhythms, and this effect was inhibited by Compound B. Compound B (30 mg/kg, i.p.) significantly potentiated the light-induced phase delay. Nociceptin induced a neuronal firing phase advance (in vitro) and locomotor activity rhythms (in vivo) in the daytime and this effect was blocked by Compound B. These results suggest that opioid receptor like 1 receptors have an inhibitory effect at night, and a facilitative effect in the day, on phase changes.

Action Potentials↗

PubMed2005

The influence of liquid crystal display (LCD) monitors on observer performance for the detection of nodular lesions on chest radiographs.

PURPOSE: To access the influence of liquid crystal display (LCD) monitors on the detectability of nodular lesions depicted on chest radiographs by comparing them with a high-resolution cathode ray tube (CRT) monitor. MATERIAL AND METHODS: Ten radiologists interpreted 247 soft-copy images on LCD monitors with pixel arrays of 1,024x1,280, 1,200x1,600, 1,536x2,048 and 2,048x2,560, and a CRT monitor with a pixel array of 2,048x2,560, and were asked to indicate their individual confidence levels regarding the presence of a nodule. These images were chest radiographs with and without a lung nodule from the "Standard Digital Image Database" created by the Japanese Society of Radiological Technology. The luminance distributions of all monitors were adjusted to the same, and the ambient illumination was 200 lux. Observer performance was analyzed in terms of the receiver-operating characteristics. RESULTS: No significant statistical differences in nodule detection performance were found among the four LCD monitors and the CRT monitor. CONCLUSION: The nodule detection performance on the LCD monitors with a spatial resolution higher than a matrix size of 1,024x1,280 was found to be equivalent to that on the high-resolution CRT monitor.

Analysis of Variance↗

PubMed2005

Low-level cadmium exposure in Toyama City and its surroundings in Toyama prefecture, Japan, with references to possible contribution of shellfish intake to increase urinary cadmium levels.

OBJECTIVES: This study was initiated to examine if exposure to cadmium (Cd) was high also outside of the previously identified Itai-itai disease endemic region in the Jinzu River basin in Toyama prefecture in Japan. METHODS: Morning spot urine samples were collected in June-August 2004 from 651 adult women (including 535 never-smokers) in various regions in Toyama prefecture, and subjected to urinalyses for cadmium (Cd), alpha1-microglobulin (alpha1-MG), beta2-microglobulin (beta2-MG), N-acetyl-beta-D-glucosaminidase (NAG), specific gravity (SG or sg) and creatinine (CR or cr). Three months later, the second urine samples were collected from those with elevated Cd in urine (e.g., > or =4 microg/g cr), together with answers to questionnaires on shellfish consumption. RESULTS: The geometric mean (GM) Cd, alpha1-MG, beta2-MG and NAG (after correction for CR) for the total participants were 2.0 microg/g cr, 2.4 mg/g cr, 104 microg/g cr and 2.8 units/g cr, respectively; further analysis with never-smoking cases only did not induce significant changes in these parameters. Analyses of the second urine samples from the high Cd subjects showed that there was substantial decrease (to about a half) in Cd in the 3-month period, and that the decrease was accompanied by reduction in alpha1-MG and NAG (beta2-MG did not show elevation even in the first samples). The urinalysis results in combination with the results of the questionnaire survey suggest that the high urinary Cd was temporary and might be induced by intake of shellfish that is edible whole. CONCLUSIONS: The overall findings appear to suggest that Cd exposure in Toyama populations (outside of the Itai-itai disease endemic region) was at the levels commonly observed on the coast of the Sea of Japan, and that the Cd level in urine might be modified by the intake of some types of seafood. Further studies are necessary to elucidate the relation of urinary Cd with seafood intake.

Acetylglucosaminidase↗

PubMed2005

Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle.

We previously reported that tumor necrosis factor alpha (TNF-alpha) was one of the cytokines that contributed to the leukemogenesis caused by bovine leukemia virus (BLV). To determine if the spontaneous cell proliferation observed in the late disease stages, such as persistent lymphocytosis and lymphosarcoma, correlated with the expression level of TNF-alpha, we analyzed the mRNA expression levels for TNF-alpha in spontaneously proliferating PBMCs derived from BLV-infected cattle. The mean mRNA expression level for TNF-alpha was higher in the spontaneously proliferating PBMCs derived from BLV-infected cattle than in non-spontaneously proliferating PBMCs from normal cattle. The TNF-alpha protein level in the PBMCs was determined by flow cytometric analysis, and it was noted that most of the cells expressing membrane-bound TNF-alpha in the spontaneously proliferating cells were CD5+ or sIgM+-cells. Additionally, in order to determine if this spontaneous proliferation can be blocked by anti-bovine TNF-alpha MAb, the spontaneously proliferating PBMCs from a BLV-infected cattle were cultured in the presence of the MAb. The addition of this MAb at the beginning of the 72 h-cultivation clearly inhibited spontaneous proliferation of cells in a dose-dependent manner, indicating the direct involvement of TNF-alpha in the spontaneous proliferation of PBMCs during the late disease stage. These data suggest that an aberrant expression of TNF-alpha might contribute to the progression of bovine leukosis in animals which develop persistent lymphocytosis of B-cells or B-cell lymphosarcoma.

Animals↗

PubMed2005

A horse of a different colour: do patients with semantic dementia recognise different versions of the same object as the same?

Ten patients with semantic dementia resulting from bilateral anterior temporal lobe atrophy, and 10 matched controls, were tested on an object recognition task in which they were invited to choose (from a four-item array) the picture representing "the same thing" as an object picture that they had just inspected and attempted to name. The target in the response array was never physically identical to the studied picture but differed from it - in the various conditions - in size, angle of view, colour or exemplar (e.g. a different breed of dog). In one test block for each patient, the response array was presented immediately after the studied picture was removed; in another block, a 2 min filled delay was inserted between study and test. The patients performed relatively well when the studied object and target response differed only in the size of the picture on the page, but were significantly impaired as a group in the other three type-of-change conditions, even with no delay between study and test. The five patients whose structural brain imaging revealed major right-temporal atrophy were more impaired overall, and also more affected by the 2 min delay, than the five patients with an asymmetric pattern characterised by predominant left-sided atrophy. These results are interpreted in terms of a hypothesis that successful classification of an object token as an object type is not a pre-semantic ability but rather results from interaction of perceptual and conceptual processing.

Adult↗

PubMed2005

No association of serotonin transporter gene (SLC6A4) with schizophrenia and bipolar disorder in Japanese patients: association analysis based on linkage disequilibrium.

Serotonin transporter gene (SLC6A4) is one of the most promising candidate genes for psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BP). Two functional polymorphisms, 5HTTLPR and 5HTTVNTR, have been a focus for genetic association analyses; however, no conclusive results have been obtained. We conducted, 1) a mutation search of SLC6A4, 2) LD mapping to select 'tagging' markers (10 SNPs and 5HTTVNTR, while 5HTTLPR was treated as an independent marker because of its allelic form), and 3) association analysis of these 'tagging' markers and independent markers (5HTTLPR and Asn605Lys) with SCZ and BP in Japanese patients. In this mutation search, a nonsynonymous SNP, Asn605Lys, was detected. No associations of 'tagging' markers and independent markers with such conditions were found. These results indicate that SLC6A4 might not play a major role in SCZ and BP in Japanese patients, a finding that agrees with both the common disease-common variant hypothesis and common disease-rare variant hypothesis.

Adult↗

PubMed2005

Smoking-induced increase in urinary cadmium levels among Japanese women.

OBJECTIVE: To examine if cigarette smoking will induce elevation in cadmium (Cd) in urine. METHODS: Information on smoking habits, and urinary levels of cadmium (Cd-U), alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), creatinine (CR or cr), and urine specific gravity (SG or sg) was cited from a combination of three previously established databases on adult Japanese women. After exclusion of those with unclear answers on smoking habits (412 cases), the combination (12,846 cases) gave 11,092, 1420 and 334 cases of never, current and former smokers, respectively, for present statistical analyses. RESULTS: Multiple regression analyses taking Cd-U as a dependent variable and 11 regions of urine collection, age and smoking habits as independent variables showed that age and regions were powerful confounders in the analysis for the effects of smoking on Cd-U. To exclude the confounding effects, current and former smokers were paired with age- and region-matched never smoking controls in subsequent analyses. In addition, former smokers were paired with age- and region-matched current smokers. The comparison of the paired cases showed that Cd-U for current smokers was significantly higher than that for never smokers. The levels for former smokers were however not higher than the levels for never smokers. When classified by the number of cigarettes consumed per day, Cd-U for current smokers increased dependently to the number of cigarettes (about 0.09 microg/cigarette/day) with leveling off at 15 or more cigarettes. There was a subtle cigarette dose-dependent increase in alpha(1)-MG, but the increase was insignificant in case of beta(2)-MG. Estimation of the amount of Cd absorbed due to cigarette smoking followed by comparison with the increase in Cd-U suggested that almost all Cd absorbed will be excreted into urine. CONCLUSIONS: Among currently smoking Japanese women, cadmium in urine increased in a manner dependent to the number of cigarettes consumed daily. Thus, smoking is a confounder of Cd-U evaluation even among the population with relatively high dietary Cd burden.

Adult↗

PubMed2005

Complete nucleotide sequence of the new potexvirus "Alstroemeria virus X". Brief report.

A flexuous virus was isolated in Japan from an alstroemeria plant showing mosaic symptoms. The virus had a broad host range but had systemically latent infectivity in alstroemeria. The virus was assigned to the genus Potexvirus based on morphology and physical properties and on an analysis of the complete nucleotide sequence. The genomic RNA of the virus was 7,009 nucleotides in length, excluding the 3'-terminal poly (A) tail. It contained five open reading frames (ORFs), which was consistent with other members of the genus Potexvirus. Although nucleotide sequences of the ORFs differ from previously reported potexviruses, a phylogenetic analysis placed it phylogenetically close to Narcissus mosaic virus and Scallion virus X. Therefore, we propose that this virus should be designated as Alstroemeria virus X (AlsVX).

Alstroemeria↗

PubMed2005

Decreases in urine specific gravity and urinary creatinine in elderly women.

OBJECTIVE: To examine the effects of aging on urinary levels of creatinine (CR) and urine specific gravity (SG) among women in a large-scale epidemiology survey. METHODS: Data on CR and SG in urine, together with smoking habits and menopausal status, were selected from previously established databases and combined with the results of supplemental sample collection. In total, CR and SG data were available for 11,090 never-smoking women (total group; 29-80 years of age); a subgroup of 1,851 women who lived in Kyoto was also selected from the total group. Data from the two groups were subjected to statistical analyses. In statistical evaluation, SG was converted to factor G, which was defined as (SG-1.000)x1,000. RESULTS: Classification by decade of years of age showed that both CR and SG decreased steadily as a function of advancement in age over 30 years, both in the total group and in the Kyoto subgroup, showing high reproducibility of the observation on a whole-country basis and on a local basis. When the levels at 80 years of age were compared with those at 30 years, there was an approximately 60% and 30% decrease in CR and factor G, respectively. Thus, the effects of aging were more marked on CR than on factor G (and therefore on SG). Menopause appeared to be an influential factor in the reduction of CR and SG, separately from aging itself. CONCLUSIONS: Urinary levels of creatinine and, to a lesser extent, urine specific gravity, steadily decreased as a function of ages of over 30 years in women.

Adult↗

PubMed2005

Effects of aging on cadmium and tubular dysfunction markers in urine from adult women in non-polluted areas.

OBJECTIVES: The objectives of the present analyses were to examine if Cd and tubular dysfunction marker levels in urine show age-dependent changes among women who lived in areas with no known cadmium (Cd) pollution in Japan, and if the trends would be further modified by correction of analyte concentration in terms of urinary creatinine (CR or cr) or urine specific gravity (SG or sg). METHODS: The results of urinalysis for Cd, alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), and N-acetyl-beta-D: -glucosaminidase (NAG) concentrations together with CR and SG were cited from previously established databases. A majority of urine samples were collected in 2000-2002 from adult women (mostly at 40-60 years of age) in various areas in Japan, and the collection was supplemented by cases of > or =60-year-old women in 2003. In total, 11,090 never-smoking cases were subjected to statistical analysis. The values as observed (e.g., Cd(ob)), together with after correction for CR (e.g., Cd(cr)) or SG (e.g., Cd(sg)), were examined by linear regression analysis after logarithmic conversion. RESULTS: The geometric mean (GM) values for Cd were 1.10 microg/l (as observed) or 1.32 microg/g cr (after correction for creatinine concentration). No increases were found in the levels of alpha(1)-MG, beta(2)-MG or NAG on a group basis, in agreement with the conditions that there was no known environmental pollution with Cd in the sampling areas. There were almost linear increases in logarithm of Cd, alpha(1)-MG, beta(2)-MG and NAG concentrations as age advanced. As CR, and to a lesser extent SG, also decreases steadily throughout life, the correction of the analyte concentrations for urine density induced substantial increases in the analyte values; i.e., the correction by CR and SG induced amplification of the increases by two- and 1.4-times, respectively, compared with the increase in non-corrected observed values. CONCLUSIONS: There were age-related increases in Cd and tubular dysfunction markers in urine among women in areas with no known Cd pollution. The increase was amplified two- or 1.4-times when CR or SG correction was applied, respectively. The observation suggests that care should be practiced in applying CR or SG correction, especially when evaluation of Cd exposure and resulting health effects is made among elderly populations.

Aging↗

PubMed2005

No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to Japanese schizophrenia.

Calcineurin, one of the serine/threonine protein phosphatase, comprises more than 1% of the total protein content in brain. This evidence points towards important roles of calcineurin in neural function. Miyakawa et al. reported that forebrain-specific calcineurin knockout mice showed the behavioral abnormalities that are often observed in schizophrenia patients. Based on this evidence, they suggested that calcineurin dysfunction could be involved in schizophrenia pathogenesis. Thereafter this report, Gerber et al. performed transmission disequilibrium test (TDT) studies and showed an evidence for a nominally significant over-transmission of a common haplotype of the human calcineurin A gamma subunit gene (PPP3CC). We performed association analysis of PPP3CC in Japanese sample of 457 schizophrenia cases and 429 controls. To our regret, we could not confirm the association with Japanese schizophrenia to PPP3CC including core at-risk haplotype. Our result suggests that PPP3CC may not play a major role in Japanese schizophrenia.

Calcineurin↗

PubMed2005

Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastases.

BACKGROUND: Autonomic nerve preservation has been advocated as a means of preserving urinary and sexual function after surgery for rectal cancer, but may compromise tumour clearance. The aim of this study was to determine the incidence of micrometastasis in the connective tissues surrounding the pelvic plexus. METHODS: The study included 20 consecutive patients who underwent rectal surgery with bilateral lymph node dissection for advanced cancer. A total of 78 connective tissues medial and lateral to the pelvic plexus and 387 lymph nodes were sampled during surgery. All connective tissue samples and 260 lymph nodes were examined for micrometastases by reverse transcriptase-polymerase chain reaction (RT-PCR) after operation. All patients were followed prospectively for a median of 36.0 months. RESULTS: Of 245 histologically negative lymph nodes, 38 (15.5 per cent) were shown by RT-PCR to harbour micrometastases. However, micrometastases to tissues surrounding the pelvic plexus were detected in only two (3 per cent) of 78 tissues, that is in two of 20 patients. Clinical follow-up showed that the two patients had a poor prognosis owing to distant metastases. CONCLUSION: Autonomic nerve-preserving surgery may be feasible for advanced rectal cancer, but study of more patients positive for micrometastases is required.

Adult↗

PubMed2005

Reproducibility of urinary cadmium, alpha1-microglobulin, and beta2-microglobulin levels in health screening of the general population.

The present study examined whether levels of cadmium, and alphal- and beta2-microglobulin in urine (Cd-U, ac-MG-U, and beta2-MG-U, respectively) were reproducible in urine samples collected from the same subjects on multiple occasions. For this purpose, two databases on background exposure to cadmium in Japan-one from study I between 2000 and 2001 and the other from study II in 2002-were revisited to find 231 apparently healthy, nonpregnant, nonlactating adult women who participated in both studies and thus had provided two urine samples. The databases contained information on Cd-U, alphal,-MG-U, and beta2-MG-U, creatinine (CR), and specific gravity (SG) as well as smoking and other lifestyle factors. Of the 231 women, 195 who had never smoked were selected for the present analysis. Cd-U as well as alpha1-MG-U were reproducible (e.g., with correlation coefficients [r] between study I and II results of 0.4 to 0.6) when measured on two occasions 9 to 10 months apart. The r values were lower for beta2-MG-U (r0.3). Exclusion of urine samples with inadequate urine density(i.e., CR <0.5 or >3.0 g/L or SG <1.010 or >1.030) resulted in substantial improvement of the agreements between the two measures (e.g., r = 0.6 to 0.7 for Cd-U and alpha1-MG-U). CR and SG correlated closely with each other, especially in low-density urine samples (r >0.9), and therefore the effects of CR and SG could not be evaluated separately. In the overall evaluation,single determination (i.e., without repeated urine sampling) of Cd-U and alpha1-MG-U should be acceptable, and it may also be acceptable for beta2-MG-U. Use of samples with adequate urine density rather than application of density correction to low-density urine samples in recommended.

Cadmium↗

PubMed2005

Brain oxidation is an initial process in sleep induction.

CNS activity is generally coupled to the vigilance state, being primarily active during wakefulness and primarily inactive during deep sleep. During periods of high neuronal activity, a significant volume of oxygen is used to maintain neuronal membrane potentials, which subsequently produces cytotoxic reactive oxygen species (ROS). Glutathione, a major endogenous antioxidant, is an important factor protecting against ROS-mediated neuronal degeneration. Glutathione has also been proposed to be a sleep-promoting substance, yet the relationship between sleep and cerebral oxidation remains unclear. Here we report that i.c.v. infusion of the organic peroxide t-butyl-hydroperoxide at a concentration below that triggering neurodegeneration (0.1 micromol/100 microl/10 h) promotes sleep in rats. Also, microinjection (2 nmol, 2 microl) or microdialysis (100 microM, 20 min) of t-butyl-hydroperoxide into the preoptic/anterior hypothalamus (POAH) induces the release of the sleep-inducing neuromodulators, nitric oxide and adenosine, without causing neurodegeneration. Nitric oxide and adenosine release was inhibited by co-dialysis of the N-methyl-D-aspartate receptor antagonist, d(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 1 mM), suggesting that glutamate-induced neuronal excitation mediates the peroxide-induced release of nitric oxide and adenosine. Indeed, Ca2+ release from mitochondria and delayed-onset Ca2+ influx via N-methyl-D-aspartate receptors was visualized during peroxide exposure using Ca2+ indicator proteins (YC-2.1 and mitochondrial-targeted Pericam) expressed in organotypic cultures of the POAH. In the in vitro models, t-butyl-hydroperoxide (50 microM) causes dendritic swelling followed by the intracellular Ca2+ mobilization, and D-AP5 (100 microM) or glutathione (500 microM) inhibited t-butyl-hydroperoxide-induced intracellular Ca2+ mobilization and protected POAH neurons from oxidative stress. These data suggest that low-level subcortical oxidation under the control of an antioxidant system may trigger sleep via the Ca(2+)-dependent release of sleep-inducing neuromodulators in the POAH, and thus we propose that a moderate increase of ROS during wakefulness in the neuronal circuits regulating sleep may be an initial trigger in sleep induction.

Adenosine↗

PubMed2005

Protective effect of diltiazem on hepatic ischemia-reperfusion injury in rats by improving liver tissue blood flow.

BACKGROUND: Cytosolic calcium ions are known to play an important role in ischemia-reperfusion (IR) injury. However, the protective effect of calcium channel blockers remains controversial in liver IR injury. Moreover, calcium channel blockers improve hepatic IR injury not due to blocking an increase in hepatic calcium concentration. Therefore, we hypothesized that calcium antagonists protected a liver from IR injury by a vasodilatory action rather than by the inhibition of an increase in Ca2+ within parenchymal cells. This study evaluated the effects of diltiazem, a calcium channel blocker, on liver energy metabolism and blood flow after IR injury. METHODS: Twenty-seven rats underwent hepatic ischemia for 30 minutes followed by 60 minutes of reperfusion. The animals were allocated into group C (without drug); group D5 (diltiazem, 5 microg/kg per min); or group D10 (diltiazem, 10 microg/kg per min). Diltiazem was infused before laparotomy and then throughout the experiment. RESULTS: After 60 minutes of reperfusion, liver tissue blood flow and ATP concentrations were significantly higher in group D10 than the other animals (both, P < .05). Changes in ATP values strongly correlated those observed in blood flow (R = 0.80, P < .001). CONCLUSION: Diltiazem improved ATP-generating capacity during reperfusion by improving liver tissue blood flow. An improvement in hepatic tissue perfusion may be a therapeutic strategy for liver IR injury.

Animals↗

PubMed2005

Optimal initial dose of orally administered cyclosporine following intravenous cyclosporine therapy.

Conversion of the main immunosuppressive agent from tacrolimus to cyclosporine (CyA) is a valuable rescue therapy for the severe adverse effects of tacrolimus. We report our experience of the conversion in living donor liver transplantation, in which tacrolimus therapy was converted to CyA. There are few reports describing the optimal initial dose of orally administered CyA (PO CyA) after intravenously administered CyA (IV CyA). We retrospectively investigated the ratio of CyA blood concentrations at 12 hours after the initiation of PO CyA to that just before the conversion, and the ratio of the initial dose of PO CyA to the total dose of IV CyA administered during the 12 hours before the conversion. Linear regression analysis revealed a close correlation between these ratios (y = 2.7 + 5.8x, r = 0.73; P = .002). We recommend that, to maintain a similar trough level of CyA during conversion in liver transplantation, Neoral should be initiated at a ninefold greater dose than the total dose of IV CyA administered during the 12 hours before conversion.

Administration, Oral↗