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Biomedical subjects

T Hirano

Publications and source records attributed to T Hirano.

At least 109 records · Page 6Linked to original sources
PubMed2001

No evidence of accelerated atherosclerosis in a 66-yr-old chylomicronemia patient homozygous for the nonsense mutation (Tyr61-->stop) in the lipoprotein lipase gene.

Whether chylomicronemia is atherogenic or not has yet to be determined in humans. We investigated a 66-yr-old female with severe chylomicronemia resulting from a lipoprotein lipase (LPL) deficiency. The patient's plasma triglyceride level was approximately 2000 mg/dl. Both LPL activity and the mass of postheparin plasma in this patient were virtually absent. A nonsense mutation in exon 3 (Tyr61-->Stop) was identified in the patient's LPL gene, and a restriction fragment length polymorphism analysis established that the patient was homozygous for this mutation. The patient was neither a diabetic nor a smoker. Clinically, the patient had never experienced pancreatitis or angia pectoris. An examination of her carotid, femoral and coronary arteries by ultrasonogram and electrocardiogram after exercise-tolerance testing showed no accelerated atherosclerosis. This case suggests that atherosclerosis may not occur despite massive hyperlipidemia, when LPL bridging was not present due to the absence of LPL secretion and circulating mass.

Aged↗
PubMed2001

Dynamic properties, interactions and adaptive modifications of vestibulo-ocular reflex and optokinetic response in mice.

Dynamic properties of horizontal vestibulo-ocular reflex (VOR) and optokinetic response (OKR) were studied in mice. The VOR was examined in the dark (VORD), in the light (VORL) and in the condition in which most of the visual field moves synchronously with the head motion (VORF). A mouse and/or a surrounding screen with vertical stripes was rotated sinusoidally, and the gain and phase of eye movements were measured in wide dynamic stimulation ranges. The working conditions of VOR and OKR were supplementary; OKR worked at low speeds of head turn and VOR at high speeds. Examination of VORL and VORF revealed non-linear interaction of VOR and OKR. The continuous sinusoidal head oscillation coupled with the in-phase or the out-of-phase oscillation of the surrounding screen, decreased or increased the VORD gain, and increased or decreased the VORD phase lead, respectively. Continuous oscillation of the surrounding screen increased the OKR gain and decreased the phase delay. These changes of VOR and OKR work to reduce the retinal slip. The present study provides fundamental information concerning the dynamic properties of VOR and OKR and the nature of their adaptive modifications in mice, which have been extensively used in genetic manipulation recently.

Adaptation, Physiological↗
PubMed2001

Role of phosphatidylinositol-3 kinase and its association with Gab1 in thrombopoietin-mediated up-regulation of platelet function.

OBJECTIVE: Human blood platelets are easily available physiologic target cells for thrombopoietin (TPO). TPO up-regulates platelet aggregation and alpha-granule secretion induced by various agonists. We investigated the role of phosphatidylinositol 3-kinase (PI3K) and its association with Gab1 in TPO-mediated up-regulation of platelet function. MATERIALS AND METHODS: PI3K inhibitors (wortmannin and LY294002) and a MAP/ERK-kinase (MEK) inhibitor (PD98059) were used to investigate the role of these kinases in TPO-mediated up-regulation of platelet function. To elucidate the molecules associated with PI3K, we performed immunoprecipitation and pull-down experiments followed by immunoblotting. In vitro kinase assay also was performed to detect extracellular signal-regulated kinase (ERK) kinase activity. RESULTS: TPO up-regulated platelet alpha-granule secretion and aggregation induced by thrombin, which was dose-dependently inhibited by preincubation with wortmannin or LY294002. Immunoprecipitation and pull-down experiments revealed that regulatory subunit of PI3K, p85, was rapidly associated with tyrosine-phosphorylated Gab1 via its n- and c-terminal SH2 domains. Pretreatment of platelets with TPO dramatically augmented the thrombin-induced ERK activation, which was almost completely inhibited by LY294002. Furthermore, a MEK inhibitor, PD98059, not completely but significantly inhibited TPO-mediated up-regulation of thrombin-induced alpha-granule secretion. CONCLUSION: TPO induces the association of tyrosine-phosphorylated Gab1 with p85-PI3K. In downstream signaling, ERK is PI3K-dependently activated, which plays a critical role for TPO-mediated up-regulation of platelet function.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients.

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The alpha1-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2% approximately 16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6+/-0.6 nm to 25.9+/-0.4 nm (P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r=-0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.

Aged↗
PubMed2001

Treatment of chronic aortic dissection by transluminal endovascular stent-graft placement: preliminary results.

PURPOSE: To investigate efficacy of stent-graft repair for the treatment of patients with chronic aortic dissection. MATERIALS AND METHODS: Fifteen patients with chronic aortic dissection were treated with endovascular stent-grafts. Entry tears were located in the descending thoracic aorta in all patients. The mean maximum diameter of the descending thoracic aorta was 47 mm +/- 8. The mean diameter of the true lumen at the same level was 20 mm +/- 5. The mean interval between diagnosis and stent-graft procedure was 32 months +/- 91. Stent-grafts were fabricated from expanded polytetrafluoroethylene and Z-stents. RESULTS: Stent-grafts were placed successfully in all patients. Two stent-grafts were required in one patient. Entry closure and thrombosis of the false lumen of the descending thoracic aorta were also achieved in all patients. No procedure-related complications were observed except for postimplantation syndrome, including fever and leukocytosis. The diameter of the true lumen was significantly increased (mean, 31 mm +/- 6) at the level of the descending thoracic aorta (P <.01) and the diameter of the aorta was significantly decreased (mean, 44 mm +/- 8) at the same level (P <.01). There were no deaths and no instances of aortic rupture during the subsequent average follow-up period of 24 months. Secondary stent-graft procedures were required to treat the abdominal component of dissection during follow-up in one patient. CONCLUSIONS: Stent-graft repair of chronic aortic dissection is a safe and effective method and may be an alternative to surgical graft replacement in selected patients. However, further evaluation is mandatory before this method is widely employed.

Adult↗
PubMed2001

Cortisone counteracts apoptosis-inducing effect of cortisol in human peripheral-blood mononuclear cells.

Glucocorticoids (GCs) have been considered to regulate immune cell systems through induction of apoptosis in thymocytes and mature peripheral-blood lymphocytes. Here we report that apoptosis induced by cortisol in mitogen-activated peripheral-blood mononuclear cells (PBMC) is suppressed by cortisone, an oxidized metabolite of cortisol. Apoptosis in PBMCs is quantified by a cell death ELISA procedure, which can specifically detect fragmented DNA. Cortisol induced PBMC-apoptosis at concentrations more than 10 ng/ml (28 nM) in concanavalin A-stimulated PBMCs and cortisone suppressed this apoptosis at a concentration range of 1-10,000 ng/ml (2.8-28,000 nM) dose-dependently. Prednisone, a synthetic oxidized-GC, also suppressed the apoptosis-inducing effect of cortisol in a dose-dependent manner. Suppression of cortisol-induced apoptosis by cortisone was consistently observed in PBMCs derived from 16 healthy subjects. Examination for inhibitory activities of the steroids against [3H]dexamethasone binding to PBMCs suggested that cortisone can bind cellular GC-receptors (GC-Rs), but the affinity of cortisone to GCRs is 1/30 or less than that of cortisol. The results raised a possible role of cortisone in cortisol-mediated regulation of apoptosis in activated human PBMCs. The counteracting action of cortisone against cortisol-induced apoptosis may take place partially through intervention of GC-receptors (GC-Rs), but may also be due to unknown pathway(s) different from those mediated by cellular GC-Rs.

Adult↗
PubMed2001

Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles.

We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT). The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally. The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry. The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02). This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone.

Animals↗
PubMed2001

Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures.

We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However, in our previous study, 1 year treatment with high-dose etidronate (EHDP) did not increase microdamage accumulation in most skeletal sites of dogs in spite of complete remodeling suppression and the occurrence of spontaneous fractures of ribs and/or thoracic spinous processes. This study evaluates the effects of EHDP on microdamage accumulation and biomechanical properties before fractures occur. Thirty-six female beagles, 1-2 years old, were treated daily for 7 months with subcutaneous injections of saline vehicle (CNT) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechanical testing were performed. EHDP treatment suppressed intracortical and trabecular remodeling by 60%-75% at the lower dose, and by 100% at the higher dose. Osteoid accumulation caused by a mineralization deficit occurred only in the E-high group, and this led to a reduction of mineralized bone mass. Microdamage accumulation increased significantly by two- to fivefold in the rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and by twofold in the lumbar vertebra and ilium in E-high. However, no significant increase in damage accumulation was observed in ribs or thoracic spinous processes in E-high where fractures occur following 12 months of treatment. Mechanical properties of lumbar vertebrae and thoracic spinous processes were reduced significantly in both E-low and E-high. These findings suggest that suppression of bone remodeling by EHDP allows microdamage accumulation, but that osteoid accumulation reduces production of microdamage.

Animals↗
PubMed2001

N-Alkane uptake and utilisation by Streptomyces strains.

Streptomyces strains isolated from the Kuwait Burgan oil field were defined as S. griseoflavus, S. parvus, and S. plicatus utilised n-hexadecane, n-octadecane (purified fractions of mineral oil), kerosene, and crude oil as sole carbon and energy sources. The strains were incubated with n-alkanes and increase of the fatty acid content with chain length equivalent to the employed n-alkanes was observed. Signal transducing GTP-binding proteins (GBPs) play an important role in n-alkane uptake in streptomycetes. Specific activators of GBPs increased the uptake of hydrocarbons. Using the hydrophobic fluorescent dye diphenylhexatrien (DPH) as a probe, it was found that the microviscosity of the hydrophobic inner region of the cellular membrane is significantly lower in hydrocarbon utilisers than in non-utilisers. This difference probably reflects differences in the fatty acid composition of the strains. When cultures were grown in n-alkane containing media, electron microscopy revealed that the hydrocarbon utilisers showed less-electron dense areas as inclusions in the cytoplasm. Soil samples inoculated with Streptomyces strains eliminated hydrocarbons much faster than those not containing these strains, serving as control. When inorganic medium was supplied with n-hexadecane-1-14C as sole carbon and energy source, radioactive CO2 was detected. Since streptomycetes have not been used until now for oil elimination, though they are known as abundant soil bacteria tolerating extreme conditions, their possible use for bioremediation of hydrocarbon contaminated soils is discussed.

Alkanes↗
PubMed2001

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗
PubMed2001

HVJ-liposome-mediated transfection of HSVtk gene driven by AFP promoter inhibits hepatic tumor growth of hepatocellular carcinoma in SCID mice.

Suicide gene therapy using ganciclovir (GCV) with transfection of the herpes thymidine kinase (HSVtk) gene has been studied for cancer therapy. The present study demonstrates an efficient method of suicide gene therapy for multiple hepatic tumors, involving repetitive transfection of the HSVtk gene driven by the alpha-fetoprotein (AFP) promoter using hemagglutinating virus of Japan (HVJ)-liposomes. AFP-producing cells (HUH7) and AFP-nonproducing cells (LS180) were injected subcutaneously (s.c.) to establish tumors in nude mice. Two plasmid constructs, bacterial LacZ gene driven by the AFP promoter (AFPLacZ), and HSVtk gene driven by the AFP promoter (AFPTK1) were encapsulated into the HVJ-liposome and used. When AFPLacZ was injected into the s.c. tumors, expression of LacZ gene was confined to HUH7 tumors. Repeated transfection of AFPTK1 followed by GCV treatment markedly suppressed growth of HUH7 tumors, and apoptosis of HUH7 cells was recognized in the tumor. Next, HUH7 cells were injected into the portal vein in severe combined immunodeficiency mice to establish a hepatic tumor model. After inoculation with the tumor, HVJ-liposomes containing the AFPTK1 plasmid vector were injected into the portal vein via the splenic hilum, followed by GCV treatment. This gene therapy significantly inhibited the growth of tumors in the liver and markedly improved survival. Three injections of the AFPTK1 plasmid vector completely inhibited tumor growth. This procedure seems to have great potential for the treatment of multiple hepatic tumors.

Animals↗
PubMed2001

Selective enhancement of thrombopoietic activity of PEGylated interleukin 6 by a simple procedure using a reversible amino-protective reagent.

We developed a novel method for the chemical modification of cytokines with synthetic polymers to increase the therapeutic efficacy of the former in vivo. A pH-reversible amino-protective reagent, dimethylmaleic anhydride (DMMAn), was used for modification of interleukin-6 (IL-6) with polyethylene glycol (PEG). The novel PEG-conjugated IL-6 (DmPEG-IL-6), which had been pretreated with DMMAn before PEGylation, showed up to a 140% increase in in vitro specific activity compared with PEG-IL-6 that had been synthesized by the previous method. Moreover, DmPEG-IL-6 caused thrombopoiesis more potently in mice than PEG-IL-6. The DmPEG-IL-6 Fr.1, having 3-4 PEG chains attached to the cytokine, showed the strongest thrombopoietic effect among the DmPEG-IL-6s with different molecular sizes that were tested. PEG-IL-6 Fr.1 had a 500-fold higher potency in stimulating thrombopoiesis than native IL-6 and DmPEG-IL-6 Fr.1 achieved a threefold higher thrombopoietic effect than PEG-IL-6 Fr.1. In addition, side-effects, such as an increase in the plasma fibrinogen level, were not observed after injection of either PEG-IL-6s or DmPEG-IL-6s. These results suggest that PEGylation with DMMAn pretreatment may become a useful means for clinical cytokine delivery.

Animals↗
PubMed2001

Pre-emptive renal transplantation in children.

BACKGROUND: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). METHODS: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. RESULTS: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. CONCLUSION: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.

Acute Disease↗
PubMed2001

Intravenous digital subtraction angiography and helical computed tomography in evaluation of living renal donors.

OBJECTIVES: The present study was carried out to evaluate the accuracy of helical computed tomography (CT) and intravenous digital subtraction angiography (IV-DSA) on anatomical assessment of renal vasculature for living renal donors. METHODS: Forty-two healthy potential renal donors were prospectively evaluated and 35 subsequently underwent donor nephrectomy after helical CT and IV-DSA evaluation. The vascular and non-vascular findings were compared between the findings on helical CT, IV-DSA and surgery. RESULTS: Ten prehilar branches and five accessory renal arteries were found at nephrectomy. Overall, operative findings agreed with the findings by IV-DSA in 89% and by helical CT in 83%. In delineating accessory arteries, IV-DSA had a sensitivity of 60% and specificity of 97%, whereas helical CT had a sensitivity of 40% and specificity of 100%. In delineating prehilar branches, IV-DSA had a sensitivity of 90% and specificity of 100%, whereas helical CT had a sensitivity of 70% and specificity of 100%. Accessory arteries and prehilar branches that were not detected by helical CT or IV-DSA, were less than 2 mm in diameter and did not require vascular reconstruction. Renal veins were delineated in 63% by IV-DSA, whereas they were clearly imaged by helical CT in all cases, including a case with a circumaortic renal vein. Non-vascular findings were obtained in 64% by helical CT, including two renal tumors. None of these findings were obtained by IV-DSA. CONCLUSION: Helical CT and IV-DSA provide comparably sufficient information on renal artery vasculature. However, helical CT provides significantly more information on venous and non-vascular findings as a single-imaging modality.

Adult↗
PubMed2001

Assessing systemic 11beta-hydroxysteroid dehydrogenase with serum cortisone/cortisol ratios in healthy subjects and patients with diabetes mellitus and chronic renal failure.

11beta-hydroxysteroid dehydrogenase (11beta-HSD), an enzyme regulating mineralocorticoid like action of glucocorticoid, oxidizes active cortisol to inactive cortisone. Impaired activity of this enzyme is associated with apparent mineralocorticoid excess (AME) syndrome and is characterized by hypertension and hypokalemia. Recent investigations suggest the presence of hypertensive subjects with low activity of 11beta-HSD. The blood concentration ratio of cortisone/cortisol reflects the overall conversion of cortisol to cortisone and may be an index to assess the systemic activity of 11beta-HSD. We evaluated the peripheral blood concentration ratio of cortisone/cortisol as a possible marker to identify subjects with hypertension thought to represent impaired 11beta-HSD activity. We compared this ratio in healthy subjects and patients with diabetes mellitus (DM) or chronic renal failure (CRF). Peripheral blood samples were collected from 69 healthy subjects, 44 DM, and 36 CRF patients in the morning (9:00 to 11:00 AM). Twenty-six DM patients (59%) and 32 CRF patients (89%) met the criteria for having hypertension. Serum cortisol and cortisone concentrations were determined by high performance liquid chromatography (HPLC). All values for serum cortisone and cortisol levels were within the normal range. Serum cortisone/cortisol ratio in the healthy subjects was distributed with a range of 0.113 to 0.494 (median, 0.243). Compared with healthy subjects, DM and CRF patients had significantly low (P <.01) serum cortisone/cortisol levels (median, 0.188 [range, 0.092 to 0.313] in DM and 0.088 [range, 0.031 to 0.140] in CRF). Bimodal distribution of cortisone/cortisol, found in DM patients with hypertension, represented high- and low-ratio groups around the border of the ratio 0.2. Kidney function, DM duration, and complications varied between the high- and low-ratio groups. The low ratio group (<0.2), whose 11beta-HSD activity was considered low, had an increase in blood urea nitrogen (BUN) levels and experienced nephropathy, neuropathy, retinopathy, and prolonged DM duration when compared with the group with a ratio greater than 0.2. The data suggest that the serum cortisone/cortisol ratio reflects the change in 11beta-HSD activity and is dependent kidney function. This is a possible marker to evaluate glucocorticoid excess hypertension observed in DM and CRF patients.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

The combined use of prostaglandin I2 analogue (OP-2507) and thromboxane A2 synthetase inhibitor (OKY-046) strongly inhibits atherosclerosis of aortic allografts in rats.

BACKGROUND: Atherosclerosis is the main lesion in allografts undergoing chronic rejection. We investigated the effect of OP-2507 (prostaglandin I2 analogue) and OKY-046 (thromboxane A2 synthetase inhibitor) on graft atherosclerosis morphologically and the production of eicosanoids in grafts in a rat aortic allograft model. METHODS: Abdominal aortic allografts of Lewis (RT-1(l)) rats were transplanted orthotopically into fully major histocompatibility complex mismatched Wistar King A/Qdj (RT-1(u)) rats that were subcutaneously administered OP-2507 (0.1 mg/kg/d) or OKY-046 (125 mg/kg/d), or both, with an osmotic pump. Four, 8, or 12 weeks later, the grafts were harvested and examined histologically, and the concentration of eicosanoids in the grafts were analyzed. RESULTS: Lewis aortic allografts in Wistar King A recipients with no treatment displayed atherosclerosis, which involved gradual intimal thickening and medial thinning with continuous inflammation in adventitia. Neither OP-2507 nor OKY-046 treatment affected the intensity of adventitial inflammation. Although inhibition of medial thinning or a decrease in medial nuclear density was not observed, OKY-046 administration alone significantly inhibited an increase in intimal thickness. OP-2507 administration alone significantly inhibited a decrease in medial nuclear density and intimal thickening. Combined treatment with OP-2507 and OKY-046 further decreased the alteration of media and intima. The ratio of thromboxane B2 and 6-keto-prostaglandin F(1alpha) in the grafts was significantly reduced by OKY-046 but not by OP-2507 alone. CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect. Amelioration of balance in eicosanoid production in the grafts by the use of thromboxane A2 synthetase inhibitor and the simultaneous usage of stable prostaglandin I2 analogue may be a strategy for preventing atherosclerosis that results from chronic rejection.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Aneurysmal degeneration of the aorta after stent-graft repair of acute aortic dissection.

PURPOSE: Stent-graft repair of acute aortic dissection has only recently begun, and the true efficacy and safety of this technique have not yet been clarified. In this report, we describe a significant, previously unreported complication following stent-graft repair of acute aortic dissection. MATERIALS AND METHODS: Fourteen patients with acute aortic dissection underwent stent-graft repair. All of the entry tears were located in the descending thoracic aorta. Five patients had type A aortic dissection, and nine patients had type B aortic dissection. The entry tears were closed with stent-grafts, which were fabricated from expanded polytetrafluoroethylene and Z-stents. RESULTS: Stent-graft placement was successfully performed without any complications in all patients. Entry closure was achieved in 13 (93%) of 14 patients. The mean follow-up period was 18 months (range, 9 days to 36 months). During this period, four patients had saccular aneurysms in the proximal descending thoracic aorta. A saccular aneurysm was noted during a mean follow-up period of 63 days (range, 38-99 days). Two of these patients were treated with stent-grafts. Conventional surgical repair is planned in one patient. The other patient is being treated with conservative management. CONCLUSIONS: Stent-graft repair is a technically feasible and effective method for the treatment of acute aortic dissection in selected patients. However, careful follow-up is mandatory to check for the development of saccular aneurysms.

Aged↗