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Biomedical subjects

Hiroyuki Furukawa

Publications and source records attributed to Hiroyuki Furukawa.

At least 37 records · Page 2Linked to original sources
PubMed2004

A new immunosuppressant, FTY720, in canine kidney transplantation: effect of single-drug, induction and combination treatments.

Three different types of treatment were conducted to clarify the properties of a novel immunomodulator, FTY720, in canine kidney allograft models. Survival, biochemical and hematological tests, pharmacokinetics, and histopathology of grafts and extra-renal organs were analyzed. Accompanying a remarkable reduction in circulating lymphocytes, single-drug treatment of FTY720, ranging from 0.05 to 10 mg/kg, exhibited significant prolongation of graft survival without a dose-dependent effect. Short-course induction with FTY720 at 5 mg/kg per day exhibited similar anti-rejection effects as did single-drug treatment but no advantage in rescuing ongoing rejection. In combination with cyclosporine (CsA; 5 mg/kg) or tacrolimus (FK; 0.5 mg/kg), FTY720 had an additive effect. Trough blood concentrations of FTY720 were linearly correlated with dose. No animal showed critical adverse effects at any point. FTY720 holds promise as a candidate in a new category of drugs that can be combined with conventional agents for induction and maintenance immunosuppression in clinical organ transplantation.

Animals↗
PubMed2004

Cadaveric domino liver transplantation: the first case in Japan.

The first case of domino liver transplantation from a brain-dead donor in Japan is described. A 49-year-old man with familial amyloidotic polyneuropathy received a cadaver liver, and his native liver was transplanted into a 53-year-old man with polycystic liver and kidney disease. The cadaveric liver allograft was transplanted by the conventional technique. The graft taken from the first recipient had four outflow orifices (the left, middle, and right hepatic veins, and upper vena cava), for which a single orifice was created at the back table. This graft was transplanted in piggy-back fashion. The first recipient developed acute rejection on day 13 and hepatic artery stenosis on day 36. These were treated by steroid recycle therapy and percutaneous transarterial angioplasty. He was discharged on day 57 with normal liver function. The second recipient underwent re-operation for bleeding from the right adrenal gland and left thoracic cavity. He was diagnosed with acute rejection on day 7, which was treated by steroid pulse therapy. He was discharged uneventfully on day 39 with normal liver function.

Amyloid Neuropathies, Familial↗
PubMed2004

Dipyridamole protects the liver against warm ischemia and reperfusion injury.

BACKGROUND: Adenosine, a metabolite of adenosine triphosphate degradation during ischemia, is reported to attenuate ischemia and reperfusion injury in several tissues. Dipyridamole is a nucleoside transport inhibitor that augments endogenous adenosine. In this study, we tested whether dipyridamole would attenuate hepatic I/R injury. For this purpose, dipyridamole was applied to a 2-hour total hepatic vascular exclusion model in dogs. STUDY DESIGN: Dipyridamole (DYP) was given by continuous intravenous infusion for 1 hour before ischemia at a dose of 0.25 mg/kg (high-DYP, n = 6), 0.1 mg/kg (medium-DYP, n = 6), or 0.05 mg/kg (low-DYP, n = 6). Nontreated animals were used as ischemic controls (CT, n = 12). Two-week survival, systemic and hepatic hemodynamics, liver function tests, energy metabolism, adenosine 3', 5'-cyclic monophosphate (cyclic AMP) levels, platelet numbers, arachidonic acid metabolites, and histopathology were analyzed. RESULTS: Two-week animal survival was 25% in CT, 17% in high-DYP, 100% in medium-DYP, and 17% in low-DYP. Dipyridamole significantly improved postreperfusion hepatic blood flow and energy metabolism, attenuated liver enzyme release and purine catabolite production, and augmented cyclic AMP levels. The medium dose of dipyridamole lessened platelet aggregation, thromboxane B2 production, and polymorphonuclear neutrophil infiltration, and improved survival. CONCLUSIONS: We demonstrated marked hepatoprotective effects of dipyridamole against severe ischemia and reperfusion injury in canine livers. Dipyridamole is a promising agent for liver surgery and transplantation.

Animals↗
PubMed2004

The variability of liver graft function and urinary 6beta-hydroxycortisol to cortisol ratio during liver regeneration in liver transplant recipients.

The urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) is considered to be the simplest and most practical method for estimation of hepatic cytochrome P450 3A4 (CYP3A4) activity as a non-invasive marker of human in vivo CYP3A4 activity. However, the inter- and intra-individual variability of the urinary 6beta-OHF/F ratio during liver regeneration and the effect of variability on optimal dose of tacrolimus have not yet been clarified. The objective of this study was to clarify the change in the urinary 6beta-OHF/F ratio during liver regeneration and to determine the effect of the liver graft function on the optimal tacrolimus dose in liver transplant recipients. Two liver transplant recipients (one male and one female) and eight healthy volunteers (five males and three females) were enrolled in this study. Urine samples were collected from the recipients from 08.00 hours for 24 h on post-transplant period, 1-10 and 21-30 days postoperatively. In the healthy volunteers, morning spot urine samples were collected at 08.00 hours. The mean urinary 6beta-OHF/F ratio in the immediate postoperative period was significantly low (p < 0.05). However, a marked difference in the regulation of CYP3A4 activity during liver regeneration was found in the two recipients. A significant correlation was found between the urinary 6beta-OHF/F ratio and the C/D ratio of tacrolimus (R = 0.658, p < 0.05). The urinary 6beta-OHF/F ratio is a useful probe for estimating the variability of CYP3A4 activity in liver transplant recipients in early postoperative phase. Future studies should evaluate the clinical usefulness of the urinary 6beta-OHF/F ratio as a predictor of tacrolimus pharmacokinetics in liver transplantation.

Adult↗
PubMed2004

Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan.

OBJECTIVE: We sought to determine the outcome of living donor liver transplantation (LDLTx) in 316 adult patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: LDLTx has increasingly been performed worldwide, but the impact of the procedure on HCC has not been evaluated in a large series. METHODS: Between October 1989 and December 2003, 1389 adults underwent LDLTx at 49 centers in Japan. In 316 (22.8%) who received LDLTx for HCC (70 females, 22%, median age 57 years; and 246 males, 88%, median age, 54 years), we analyzed pretransplant clinical status, imaging diagnosis, transplant procedure, pathologic study of explanted liver, and outcome. In 232 patients (73.4%), various surgical and nonsurgical therapies had been employed prior to LDLTx. The median follow-up period was 16 months (range, 2.5-72.0) RESULTS: Currently, 236 (74.7%) of the patients are living. One- and 3-year patient survivals were 78.1% and 69.0%, respectively. Model end-stage liver disease score and preoperative serum alpha-fetoprotein level were independent risk factors for patient survival. Forty patients (12.7%) developed HCC recurrence. Alpha-fetoprotein level, tumor size, vascular invasion, and bilobar distribution were independent risk factors for HCC recurrence. Grade of histologic differentiation of HCC showed close correlation with tumor characteristics and recurrence. One- and 3-year recurrence-free survivals were 72.7% and 64.7%, respectively. When the Milan criteria were applied, patient survival and disease-free survival at 3 years were 78.7% and 79.1%, respectively, in patients who met the criteria, and 60.4% and 52.6%, respectively, in those who did not. CONCLUSION: LDLTx can achieve acceptable survival in HCC patients, even when liver function is markedly impaired, or HCC is uncontrollable by conventional antitumor treatments.

Adult↗
PubMed2004

Disposition kinetics of taxanes after intraperitoneal administration in rats and influence of surfactant vehicles.

Rats were intraperitoneally administered 40 mg x kg(-1) of paclitaxel or docetaxel dissolved in various drug solutions. The drug solutions were prepared using 20 mL of saline, adding 4.2% Cremophor EL (crEL) for paclitaxel (TXL), and 1.5% Polysorbate-80 (PS-80) (TXT), 7.5% PS-80 (TXT+PS-80) or 4.2% crEL (TXT+crEL) for docetaxel. The apparent first-order absorption rate constant from the peritoneal cavity (k(a)) of TXL was about one-twentieth of that of TXT. The ratio of the area under the concentration-time curve of drug in plasma over that in ascites for TXL was about one-third of that of TXT. The values of the above ratio and the k(a) of TXT+PS-80 and TXT+crEL were similar to those of TXL. After intraperitoneal administration, the values of the blood-to-plasma concentration ratio in the four groups were similar and independent of time. In the in-vitro study, PS-80 and crEL caused similar, concentration-dependent decreases of drug permeation into red blood cells after a 15-min incubation of rat blood with 10 microg x mL(-1) of TXL. We demonstrated that the disposition kinetics of taxanes after intraperitoneal administration to rats was strongly influenced, in a concentration-dependent manner, by the surfactant vehicle used, crEL or PS-80.

Animals↗
PubMed2004

Peripheral anatomic evaluation using 3D CT hepatic venography in donors: significance of peripheral venous visualization in living-donor liver transplantation.

OBJECTIVE: The purpose of this study was to determine clinical roles for 3D CT hepatic venography in the evaluation of peripheral hepatic venous anatomy during living-donor liver transplantation. MATERIALS AND METHODS: Subjects comprised 54 donors (age range, 20-60 years) who had undergone surgery to donate a liver for transplantation. Visualization of each hepatic venous branch and total visualization using 3D CT hepatic venography were evaluated. Maximum venous branch order visualized was graded as nil, first branch, second branch, or third branch or more. The distance between the hepatic surface and the tip of each hepatic venous branch was classified as 0-5 mm, 6-10 mm, 11-15 mm, 16-20 mm, or 21-25 mm. Quality of total 3D CT hepatic venography was evaluated subjectively as poor, good, fair, or excellent. Dominance of large hepatic veins in the right lobe, peripheral branching pattern of the middle hepatic vein, and branching pattern of the vein draining segment IVb were also assessed. RESULTS: Most hepatic venous branches (96.2% [275/286]) were visualized up to at least the second-order branches, and 93.7% (268/286) of branches were within 10 mm of the hepatic surface. As for total visualization, 98% (53/54) of cases were regarded as excellent. The dominant vein in the right lobe was the right hepatic vein in 27 cases, inferior hepatic vein in 25, and middle hepatic vein in one. The branching pattern of the middle hepatic vein was type 1 in 36 cases, type 2 in nine, and type 3 in eight. Segment IVb vein branched from the middle hepatic vein in 20 patients, and from the left hepatic vein in 34. CONCLUSION: Because 3D CT hepatic venography visualizes peripheral hepatic venous branches in detail, the technique is useful for determining operative indications in living-donor liver transplantation.

Adult↗
PubMed2004

[Examination of second-line therapies following administration of low-dose TS-1+CDDP for highly-advanced gastric cancer].

Sixteen patients with highly-advanced gastric cancer were administered low-dose TS-1 and CDDP as a first-line treatment, followed by either paclitaxel or CPT-11/CDDP as a second-line treatment. The results of the 2 second-line treatments are reported herein. Overall response rate for the first-line treatment was 55.6%. For the second-line treatments, responses were noted in both the paclitaxel group and the CPT-11/CDDP group. Overall MST was 16.3 months and 1-year survival was 60%. The paclitaxel group, however, showed significantly better prognoses than the CPT-11/CDDP group. Adverse reactions to the first-line treatment were grade 3 leukopenia in 1 patient, with no other reactions over grade 2 observed. No adverse reaction greater than grade 2 was noted during administration of the second-line treatments. These results appear to present ample data that a first-line treatment of low-dose TS-1/CDDP followed by a second-line treatment of paclitaxel at 1/week in the outpatient setting yields improved prognoses and minimal adverse reactions.

Aged↗
PubMed2004

[Liver regeneration in living-donor liver transplantation].

Liver regeneration in living-donor liver transplantation is summarized from the authors' data. In donors, liver function tests recovered to within the normal range 2 weeks after surgery regardless of graft type. At 2 weeks, the volumetric recovery of the remnant liver was 65% and 80% of the original volume in right and left lobe donors, respectively. These results suggest that functional recovery occurs earlier than morphologic restoration in donors. In recipients, the factor that affected the regeneration rate in size 4 weeks after transplantation was only implanted graft size; the rate was greater in patients in whom smaller grafts were implanted. In recipients with a rate of two or more, however, high portal vein pressure and flow were observed. Further, persistent low platelet counts and hyperbilirubinemia were seen in those patients. These results indicate that size enlargement may be caused by engorgement, and functional recovery is not achieved concurrently with morphologic restoration, especially in patients with smaller grafts. In patients with fulminant hepatic failure who receive auxiliary partial orthotopic liver transplantation, sequential histopathologic observations of the diseased liver revealed that liver regeneration initiates from cytokeratin 17-positive ductules and at least 1 year is necessary for complete recovery.

Hepatocytes↗
PubMed2003

Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD40Ig plus CTLA4Ig gene therapies.

BACKGROUND: We have previously demonstrated that blockade of either CD80/86-CD28 or CD40-CD154 costimulatory pathways by using adenovirus vector coding CTLA4Ig (AdCTLA4Ig) or CD40Ig (AdCD40Ig) genes induced donor-specific tolerance in rat liver transplantation. In this study, we asked whether these gene-therapy-based costimulation blockade would induce tolerance in cardiac transplantation. METHODS: Heterotopic heart transplantation was performed in a full major histocompatibility complex (MHC) barrier combination of ACI (RT1avl) to Lewis (LEW, RT1l) rats. Vector (1 x 10(9) plaque forming unit [PFU]), AdLacZ, AdCTLA4Ig, or AdCD40Ig, was administered intravenously to recipient animals immediately after grafting, and graft survival, serum CTLA4Ig/CD40Ig levels, and graft histology were assessed. Tolerance was determined by secondary skin-graft challenging. RESULTS: Allografts of both untreated and AdLacZ controls were promptly rejected within 7 days, whereas a single treatment with AdCTLA4Ig or AdCD40Ig significantly prolonged median graft survival to 55.5 and 28.5 days, respectively. In contrast, the combined AdCTLA4Ig and AdCD40Ig gene therapy maintained high CTLA4Ig and CD40Ig levels through the posttransplant period and allowed long-term cardiac allograft survival for more than 270 days. However, both donor and third-party skin grafts were rejected in the animals who harbored cardiac grafts over 150 days. Also, typical features of chronic rejection were evident in the long-term surviving grafts. CONCLUSION: Simultaneous blockade of CD28 and CD154 pathways by AdCTLA4Ig plus AdCD40Ig induces a strong immunosuppression that allows long-term acceptance of full MHC mismatched cardiac graft in rats. This strategy, however, was not enough to induce tolerance to skin grafts and to avoid chronic rejection, as shown in the liver-transplantation model.

Abatacept↗
PubMed2003

A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats.

BACKGROUND: A Rho-ROCK signal system induces vascular contraction and neutrophil migration, both of which are characteristic features found with ischemia and reperfusion injury of the liver. We tested our hypothesis that a novel ROCK I inhibitor, Y-27632, attenuates hepatic ischemia and reperfusion injury. METHODS: Rats underwent 70% partial hepatic ischemia for 120 minutes and subsequent reperfusion. Y-27632 of 10mg/kg was given orally 1 hour before ischemia, while distilled water was given to the control animals. One week animal survival, systemic hemodynamics, hepatic tissue blood flow, liver function tests, plasma endothelin-1, serum hyaluronic acid levels, myeloperoxidase activity and malondialdehyde level in liver tissue, membrane attack complex-1 and intracellular adhesion molecule-1 staining, and histological architecture were analyzed. RESULTS: Y-27632 prolonged 1-week animal survival from 25% of untreated animals to 75% accompanied with significant amelioration of hepatic tissue blood flow, liver function tests and histological architecture without any adverse effects on systemic hemodynamics. In addition, plasma endothelin-1 and serum hyaluronic acid levels decreased markedly compared to the control, concomitant with remarkable suppression of membrane attack complex-1 stain positive neutrophils infiltration, myeloperoxidase activity and malondialdehyde level. CONCLUSION: Present study suggests that activation of a Rho-ROCK signal system is associated with ischemia and reperfusion injury of the liver, and that Y-27632 may be an attractive agent for application in major liver resection using temporary inflow occlusion and hepatic preservation.

Alanine Transaminase↗
PubMed2003

Voluntary medication error reporting program in a Japanese national university hospital.

BACKGROUND: In Japan, as in other countries, medical accidents arising from human error can seriously damage public confidence in medical services, as well as being intrinsically undesirable. OBJECTIVE: Errors voluntarily reported by the healthcare practitioners in our institution (Kanazawa University Hospital) were considered to assess the contributory factors by using the accumulated error database in the hospital information system. METHODS: Medical errors in our institution during the period from July 1, 2000, to June 30, 2002, were counted using the error reporting system database and were classified. RESULTS: The number of errors reported during the investigation period was 1378, of which 78% were reported by nursing staff. Medication errors involving administration of injectable or oral drugs to inpatients, dispensing, and prescription accounted for about 50% of that number. Among dispensing errors, 53% were detected by patients or their families and 36% by nurses. CONCLUSIONS: The best method of error prevention is to learn from previous errors. For this purpose, the error reporting program is effective. In patient safety management, it is important to take into account the potential risks of future errors, as well as to capture information about errors that have already happened. For safety management, adoption of appropriate information technology (e.g., implementation of a prescription order entry system) is effective in reducing medication errors. However, it is important to note that serious errors can also arise in computer-based systems.

Health Occupations↗
PubMed2002

Liquid chromatographic method for the determination of ganciclovir and/or acyclovir in human plasma using pulsed amperometric detection.

We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovir and/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 microg/ml plasma) or acyclovir (0.1-20 microg/ml plasma) and peak height ratio was obtained. The relative standard deviations of all standard curves were greater than or equal to 0.999. The limits of detection for ganciclovir and acyclovir quantitation were 10 ng/ml and 50 ng/ml (signal/noise >3), respectively. Daily fluctuations of plasma standard curves (n=5) for the ganciclovir and acyclovir samples were small, with relative standard deviations (RSD) of 3.3 and 4.5% (n=5), respectively. The intra-assay precision for the ganciclovir and acyclovir samples were 6.9 (n=5) and 5.5% (n=5), respectively. Inter-assay precision of ganciclovir (n=3) and acyclovir (n=3) ranged from 2.6 to 6.8% and 3.5 to 5.0%, respectively. Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration (CHDF) in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The mean (+/-SD) ratio of ganciclovir concentrations at the inlet and outlet of the dialyzer (C(outlet)/C(inlet)) was 0.56+/-0.09. The areas under the curves of ganciclovir up to 12 h postdosing (AUC(0-->12)) at the inlet and outlet of the dialyzer were 12.54 microg h/ml and 7.16 microg h/ml, respectively. The ultrafiltrate of ganciclovir was 16.6 mg. The terminal elimination half-life (T(1/2)) of ganciclovir during CHDF was 3.6 h. These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration. The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics.

Acyclovir↗
PubMed2002

Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities.

OBJECTIVE: Alpha(1)-acid glycoprotein (AAG) is a major binding protein for neutral and basic drugs because of its great drug affinity. AAG has three main genetic variants--F1, S, and A variants. Several attempts have been made to elucidate the differences in compositions of the carbohydrate moiety and structure-function relationships such as drug-binding differences. However, there have been few reports on age- and gender-related differences in compositions or concentrations of the carbohydrate moiety of AAG variants. The aim of this study was to clarify the age- and gender-related differences in carbohydrate concentrations and in drug-binding capacities of AAG glycoforms. METHODS: The sera used in this study were obtained from 32 healthy subjects (17 men and 15 women, aged 16-84 years). The AAG glycoforms were isolated by hydroxyapatite chromatography. The binding capacity of AAG to disopyramide (DP), which is a basic drug, was determined using the ultrafiltration method. The concentrations of N-acetylneuraminic acid (NeuAc) and monosaccharides in AAG were determined using high-pH anion-exchange chromatography with pulsed-amperometric detection. RESULTS: The mean plasma AAG concentration in the female subjects was significantly lower than that in the male subjects (0.67 +/- 0.12 mg/ml, mean +/- SD, in females, n = 15, versus 0.81 +/- 0.17 mg/ml in males, n = 17, P < 0.05), but no age-related differences were found (0.75 +/- 0.18 mg/ml in young subjects, n = 24, versus 0.77 +/- 0.12 mg/ml in older subjects, n = 8, n.s.). However, the degree of branching of the glycan chain in the female subjects was significantly lower than that in the male subjects (1.61 +/- 0.17 mol/mol, mean +/- SD, in females, n = 15, versus 1.75 +/- 0.23 mol/mol in males, n = 17, P < 0.05). There was a significant inverse relationship between the binding capacity of AAG to DP (Cb/AAG) and the degree of branching of the glycan chain. The binding capacity (Cb/AAG) decreased as the degree of branching in AAG glycans increased. The binding capacity (Cb/AAG) in the female subjects was significantly higher than that in the male subjects (2.79 +/- 0.59 mg/g AAG in females, mean +/- SD, n = 15, versus 2.37 +/- 0.29 mg/g AAG in males, n = 17, P < 0.05). CONCLUSION. The degree of branching of the glycan chain in AAG plays an important role in drug-binding capacity. Gender-related differences in drug-binding capacity (Cb/AAG) may be caused by differences in the ratios of the extent of branching of the glycan chain in AAG.

Adolescent↗
PubMed2002

Induction of donor-specific tolerance by adenovirus-mediated CD40Ig gene therapy in rat liver transplantation.

BACKGROUND: Blockade of CD40-CD40 ligand (CD154) costimulatory pathway with anti-CD154 antibody (Ab) prolongs allograft survival in experimental organ transplantations; however, repeated agent administration is needed to provide an adequate immunosuppression. Seeking for simple and effective approach to interfere this signaling, we applied adenovirus-mediated gene therapy by encoding CD40Ig gene (AdCD40Ig). METHODS: Liver graft from ACI (RT1av1) rat was transplanted orthotopically into LEW (RT1l) rat, and AdCD40Ig was given to animals via the penile vein immediately after grafting (n=6). RESULTS: A single treatment with AdCD40Ig at 1x10(9) plaque forming units induced specific expression of CD40Ig gene on allograft liver, produced substantial amount of the protein in the sera, and allowed indefinite graft survival. Whereas, LEW recipients given no treatment or control adenovirus vector (AdLacZ) promptly rejected ACI liver. In addition, AdCD40Ig-treated, long-term survivors accepted skin graft from the donor strain but not the third party graft. Histopathology revealed that liver structure of the long-term surviving animals was completely preserved in normal with no infiltration of mononuclear cells. CONCLUSION: Blockade of CD40-CD154 pathway by CD40Ig gene therapy is a potent alloantigen-specific immunosuppressive strategy to induce permanent acceptance of liver allograft and would be a new therapeutic candidate in a clinical liver transplantation.

Adenoviridae↗
PubMed2002

Role of cyclic nucleotides in ischemia and reperfusion injury of canine livers.

BACKGROUND: In a series of canine liver ischemia experiments, we have shown that amelioration of hepatic injury is achievable by the inhibition of vasoconstriction, cytokine production, platelet aggregation, and neutrophil infiltration. Cyclic adenosine diphosphate (cAMP) was considered to be involved in most of these events. In our study, we tested our hypothesis that augmentation of endogenous cAMP by phosphodiesterase (PDE) 3 inhibitor, amrinone (AM), or adenylate cyclase stimulator, NKH477 (NKH), could attenuate ischemia and reperfusion injury of the liver. METHODS: Thirty-six beagle dogs were used. They were divided into group CT (untreated control), group AM, group NKH, and group CB (treated by both agents). AM or NKH were administered i.v. 1 hr before ischemia (group preAM and group preNKH) or 15 min before reperfusion (pos-AM and postNKH). Combination group animals were treated only before ischemia. Animal survival, hepatic tissue blood flow, liver enzymes, platelet counts, energy metabolism, hepatic cAMP and cyclic guanosine 3',5'-cyclic monophosphate levels, and histopathology were analyzed. RESULTS: Two-week animal survival was significantly improved by pre- or posttreatment with either agent. After reperfusion, hepatic tissue blood flow, liver enzyme release, platelet counts, energy metabolism, tissue cAMP levels, and histological architecture were also ameliorated markedly. Combination of both agents induced severe liver damage and lethal hypotension. AM treatment exhibited more protective effects than NKH, particularly when it was given before ischemia. Interestingly, not only cyclic guanosine 3',5'-cyclic monophosphate, were also restored at higher levels after reperfusion by preischemia treatment. CONCLUSIONS: Administration of amrinone or NKH477 maintained hepatic tissue concentrations of cyclic nucleotides, and attenuated ischemia and reperfusion injury of the liver. Thus, regulation of hepatic tissue cyclic nucleotides is an important alternative for prevention of hepatic damage in liver preservation and surgery.

Adenosine Triphosphate↗
PubMed2002

Flow pattern exchange in the Taylor-Couette system with a very small aspect ratio.

Numerical investigation is carried out on the flow pattern exchanges found in Taylor-Couette flows between two concentric rotating cylinders. The inner cylinder rotates while the outer cylinder and both end walls are stationary. The aspect ratio (column length/gap width) is small, and its range is from 0.5 to 1.6. Previous experimental results for this range of the aspect ratio showed that the steady flow patterns are classified into three groups: the normal two-cell mode, anomalous one-cell mode and twin-cell mode. All modes found by experiments are predicted in the present numerical calculation. Besides these three flow modes, an unsteady mode is predicted, which is time dependent and fully developed. The existence of the unsteady mode is also confirmed by our experiments. When the inner cylinder starts to rotate from rest, vortices at the corners of the inner cylinder and both end walls develop, and they induce the normal two-cell mode. The flow of the anomalous one-cell mode or twin-cell mode appears after an abrupt breakdown of symmetric two-cell mode flows. During the gradual deceleration of the inner cylinder, the transitions of flow modes occur. We observed mode transitions between the normal two-cell mode and anomalous one-cell mode and mode transitions from the twin-cell mode to the normal two-cell mode, anomalous one-cell mode, and unsteady mode. The critical loci where these mode transitions appear are determined. The numerical confirmation of the twin-cell mode is a different result obtained in the present study.

Journal Article↗