Development of Pretreatment Protocols for Determination of Soybean ß-Conglycinin in Processed Soybean Foods Using Commercial ELISA Kits.

ß-Conglycinin is the major storage protein in soybeans. Pre-clinical animal models and human clinical studies have demonstrated the triglyceride-lowering effect of this protein, suggesting that it could be put into practical use as a functional food material. To date, however, there are no accurate and simple assays for quantification of ß-conglycinin. In this study, samples were pretreated by mixing them with rice flour powder prior to extraction of proteins. Then, we used commercially available ELISA kits for detection of allergens that could be present in any contaminating soybean residue. This enabled accurate and highly reproducible quantitation of ß-conglycinin content in several processed soybean foods.

Oral Administration of Okara Soybean By-Product Attenuates Cognitive Impairment in a Mouse Model of Accelerated Aging.

The microbiota-gut-brain axis has attracted increasing attention in the last decade. Here, we investigated whether okara, a soybean by-product rich in dietary fiber, can attenuate cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice by altering gut microbial composition. Mice were fed either a standard diet, or a diet containing okara (7.5% or 15%, w/w) for 26 weeks. In the memory test, the 7.5% okara-fed mice showed a longer step-through latency and the 15% okara-fed mice had a short escape latency compared with control mice. The 15% okara-fed mice displayed decreased body weight, increased fecal weight, and altered cecal microbiota composition compared with the control group; however, there was no significant difference in the serum lactic acid and butyric acid levels among these mice groups. The 7.5% okara-fed mice had significantly higher NeuN intensity in the hippocampus compared with control mice. Furthermore, a decrease in inflammatory cytokine TNF- and an increase in brain-derived neurotrophic factor (BDNF) was observed in the 7.5% okara-fed group. The expression of synthesizing enzyme of acetylcholine was increased by the okara diets, and the acetylcholine level in the brain was higher in the 7.5% okara-fed group than in the control. These suggest that oral administration of okara could delay cognitive decline without drastically changing gut microbiota.

Extracranial Soft-Tissue Tumors: Repeatability of Apparent Diffusion Coefficient Estimates from Diffusion-weighted MR Imaging.

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article.

Repeatability of derived parameters from histograms following non-Gaussian diffusion modelling of diffusion-weighted imaging in a paediatric oncological cohort.

OBJECTIVES: To examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours. METHODS: Paediatric patients (<16 years, n = 17) were scanned twice, 24 h apart, using DWI (6 b-values, 0-1000 mm-2 s) at 1.5 T in a prospective study. Tumour ROIs were drawn (3 slices) and all data fitted using IVIM, stretched exponential, and kurtosis models; percentage coefficients of variation (CV) calculated for each parameter at all ROI histogram centiles, including the medians. RESULTS: The values for ADC, D, DDCα, α, and DDCK gave CV < 10 % down to the 5th centile, with sharp CV increases below 5th and above 95th centile. K, f, and D* showed increased CV (>30 %) over the histogram. ADC, D, DDCα, and DDCK were strongly correlated (ρ > 0.9), DDCα and α were not correlated (ρ = 0.083). CONCLUSION: Perfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCα and α, making it a strong candidate for modelling multiple-b-value diffusion imaging data. KEY POINTS: • ADC has good repeatability as low 5th centile of the histogram distribution. • High CV was observed for all parameters at extremes of histogram. • Parameters from the stretched exponential model showed low coefficients of variation. • The median ADC, D, DDC α , and DDC K are highly correlated and repeatable. • Perfusion/kurtosis parameters showed high CV variations across their histogram distributions.

Feasibility and applicability of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in routine assessments of children with high-grade gliomas.

Diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have been used as imaging biomarkers in adults with high-grade gliomas (HGGs). We incorporated free-breathing DW-MRI and DCE-MRI, at a single time point, in the routine follow-up of five children (median age 9 years, range 8-15) with histologically confirmed HGG within a prospective imaging study. It was feasible to incorporate DW-MRI and DCE-MRI in routine assessments of children with HGG. DW and DCE parameters were repeatable in paediatric HGG. Higher median ADC100-1000 significantly correlated with longer survival in our sample.

Multi-centre reproducibility of diffusion MRI parameters for clinical sequences in the brain.

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice-water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub-regions. A mixed effect model was used to measure the intra- and inter-scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra- and inter-scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra-scanner CV of 8.4% and inter-scanner CV of 24.8%. No major difference in the inter-scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra-scanner reproducibility, with the inter-scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter-scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi-centre clinical studies and trials.

Demonstration of the reproducibility of free-breathing diffusion-weighted MRI and dynamic contrast enhanced MRI in children with solid tumours: a pilot study.

OBJECTIVES: The objectives are to examine the reproducibility of functional MR imaging in children with solid tumours using quantitative parameters derived from diffusion-weighted (DW-) and dynamic contrast enhanced (DCE-) MRI. METHODS: Patients under 16-years-of age with confirmed diagnosis of solid tumours (n = 17) underwent free-breathing DW-MRI and DCE-MRI on a 1.5 T system, repeated 24 hours later. DW-MRI (6 b-values, 0-1000 sec/mm(2)) enabled monoexponential apparent diffusion coefficient estimation using all (ADC0-1000) and only ≥100 sec/mm(2) (ADC100-1000) b-values. DCE-MRI was used to derive the transfer constant (K(trans)), the efflux constant (kep), the extracellular extravascular volume (ve), and the plasma fraction (vp), using a study cohort arterial input function (AIF) and the extended Tofts model. Initial area under the gadolinium enhancement curve and pre-contrast T1 were also calculated. Percentage coefficients of variation (CV) of all parameters were calculated. RESULTS: The most reproducible cohort parameters were ADC100-1000 (CV = 3.26%), pre-contrast T1 (CV = 6.21%), and K(trans) (CV = 15.23%). The ADC100-1000 was more reproducible than ADC0-1000, especially extracranially (CV = 2.40% vs. 2.78%). The AIF (n = 9) derived from this paediatric population exhibited sharper and earlier first-pass and recirculation peaks compared with the literature's adult population average. CONCLUSIONS: Free-breathing functional imaging protocols including DW-MRI and DCE-MRI are well-tolerated in children aged 6 - 15 with good to moderate measurement reproducibility. KEY POINTS: • Diffusion MRI protocol is feasible and well-tolerated in a paediatric oncology population. • DCE-MRI for pharmacokinetic evaluation is feasible and well tolerated in a paediatric oncology population. • Paediatric arterial input function (AIF) shows systematic differences from the adult population-average AIF. • Variation of quantitative parameters from paired functional MRI measurements were within 20%.

Ultrasonographic findings and the clinical results of treatment for lymphedema.

We undertook this study using ultrasonography to examine structural changes occurring in the subcutaneous tissue with lymphedema. Ultrasonographic images were taken in 178 outpatients and 29 inpatients, with the images of the subcutis fluid accumulation, which was categorized into three types ( grade 0: absent, grade 1: a minimal amount of water, grade 2: stone-paved image due to excess water). Initial percentage of excess volume was correlated with the tissue fluid (grade 0: 7.5%, grade 1: 17.1%, grade 2: 30.5%, p <0.01). The higher the grade of fluid accumulation, the more important was the absolute reduction of lymphedema volume (grade 0: 2.5%, grade 1: 14.8%, grade 2: 33.2%, p <0.01). The percentage of severe lymphedema (stage2b + 3) was higher in inpatients than outpatients(89.3% vs. 45.8%), however, a significant decrease in the percentage of volume reduction was found for inpatients (29.4 ± 15.1% vs. 15.4 ± 14.2%, p <0.01). Echographic images can help to determine whether compression therapy will reduce lymphedema and to evaluate the treatment results by measuring tissue fluid. For severe lymphedema, a compression bandage was more effective than an elastic stocking. (English translation of Jpn J Phlebol 2013; 24: 287-294).

[Epidural anesthesia for femoral head replacement in a spinocerebellar ataxia patient: a case report].

Perioperative management of a spinocerebellar ataxia patient by epidural anesthesia is reported. A 67-year-old woman with left femur neck fracture underwent femoral head replacement. An epidural catheter was placed without difficulty at the L3-4 interspace using the loss of resistance technique. A total of 1% mepivacaine 13 ml was administered in divided doses to obtain bilateral T5 analgesic level. Hypotension (79 mmHg systolic) was observed transiently, and ephedrine 8 mg was administered which successfully elevated blood pressure. Overall, hemodynamics and respiratory status were stable. Postoperative analgesia was maintained by infusion of 0.2% ropivacaine at 2 ml x hr(-1). The patient's postoperative course was uneventful, and her neurologic conditions remained unchanged.

Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors siglec-7 and -9.

Immune cells are known to express specific recognition molecules for cell surface glycans. However, mechanisms involved in glycan-mediated cell-cell interactions in mucosal immunity have largely been left unaccounted for. We found that several glycans preferentially expressed in nonmalignant colonic epithelial cells serve as ligands for sialic acid-binding Ig-like lectins (siglecs), the immunosuppressive carbohydrate-recognition receptors carried by immune cells. The siglec ligand glycans in normal colonic epithelial cells included disialyl Lewis(a), which was found to have binding activity to both siglec-7 and -9, and sialyl 6-sulfo Lewis(x), which exhibited significant binding to siglec-7. Expression of these siglec-7/-9 ligands was impaired upon carcinogenesis, and they were replaced by cancer-associated glycans sialyl Lewis(a) and sialyl Lewis(x), which have no siglec ligand activity. When we characterized immune cells expressing siglecs in colonic lamina propriae by flow cytometry and confocal microscopy, the majority of colonic stromal immune cells expressing siglec-7/-9 turned out to be resident macrophages characterized by low expression of CD14/CD89 and high expression of CD68/CD163. A minor subpopulation of CD8(+) T lymphocytes also expressed siglec-7/-9. Siglec-7/-9 ligation suppressed LPS-induced cyclooxygenase-2 expression and PGE(2) production by macrophages. These results suggest that normal glycans of epithelial cells exert a suppressive effect on cyclooxygenase-2 expression by resident macrophages, thus maintaining immunological homeostasis in colonic mucosal membranes. Our results also imply that loss of immunosuppressive glycans by impaired glycosylation during colonic carcinogenesis enhances inflammatory mediator production.

Neuroendocrine tumor liver metastases: use of dynamic contrast-enhanced MR imaging to monitor and predict radiolabeled octreotide therapy response.

PURPOSE: To evaluate dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for monitoring and assessing treatment response in patients with neuroendocrine liver metastases treated using yttrium 90 ((90)Y)-labeled octreotide ((90)Y-DOTATOC). MATERIALS AND METHODS: The study was approved by the local research and ethics committee and patient informed consent was obtained. Twenty patients with liver metastases from neuroendocrine tumors underwent T1-weighted DCE MR imaging of the liver before and at 2 months after intravenous (90)Y-DOTATOC treatment. Regions of interest were drawn around target lesions, as well as along liver outlines for each patient. A dual-input single-compartment model was used to compute parameters including fractional distribution volume and the arterial flow fraction. Pre- and posttreatment values were compared using Wilcoxon signed rank test. Treatment response was defined as showing a greater than 50% reduction in the nadir chromogranin A level within the 1st year after treatment. Pretreatment values of responders and nonresponders were compared using the Mann-Whitney test. A two-tailed P value of .008 or less, which accounts for multiple testing, was considered to indicate a significant difference. RESULTS: In responders, tumor and whole liver distribution volume significantly increased after treatment (median tumor distribution volume, 0.182 vs 0.244; median whole liver distribution volume, 0.175 vs 0.207; P = .008). The pretreatment whole liver distribution volume was significantly lower in responders (median, 0.175 vs 0.248; P = .003), while pretreatment tumor arterial flow fraction was significantly higher in responders (median, 1.000 vs 0.7 ± 1, P = .006). CONCLUSION: DCE MR imaging may be used to monitor the effects of peptide receptor radiolabeled targeted therapy in patients with neuroendocrine tumors liver metastases; a lower pretreatment distribution volume and high arterial flow fraction was associated with a better response to treatment.

Hypercholesterolemia and oxidative stress inhibit endothelial cell healing after arterial injury.

OBJECTIVE: Endothelial cell (EC) migration is essential for arterial healing after angioplasty. Oxidized low-density lipoproteins and oxidative stress decrease EC migration in vitro. The objective of this study was to determine the effect of hypercholesterolemia and oxidative stress on EC healing after an arterial injury. METHODS: C57BL/6 wild-type mice were placed in one of eight groups: chow diet (n = 11), high-cholesterol (HC) diet (n = 11), chow diet plus paraquat (n = 11), HC diet plus paraquat (n = 11), chow diet plus N-acetylcysteine (NAC) (n = 11), HC diet plus NAC (n = 11), chow diet plus paraquat and NAC (n = 11), and HC diet plus paraquat and NAC (n = 11). After 2 weeks on the assigned diet with or without NAC, the carotid artery was injured using electrocautery. Animals in the paraquat groups were given 1 mg/kg intraperitoneally to increase oxidative stress. After 120 hours, Evans Blue dye was infused intravenously to stain the area of the artery that remained deendothelialized. This was used to calculate the percentage of re-endothelialization. Plasma and tissue samples were analyzed for measures of oxidative stress. RESULTS: The HC diet increased oxidative stress and reduced EC healing compared with a chow diet, with EC covering 26.8% ± 2.8% and 48.1% ± 5.2% (P < .001) of the injured area, respectively. Administration of paraquat decreased healing in both chow and HC animals to 18.1% ± 3.5% (P < .001) and 9.8% ± 4.6% (P < .001), respectively. Pretreatment with NAC (120 mmol/L in drinking water) for 2 weeks prior to injury, to decrease oxidative stress, improved EC healing to 39.9% ± 5.7% (P < .001) in hypercholesterolemic mice and to 30.7% ± 3.6% (P < .001) in the paraquat group. NAC treatment improved healing to 24.6% ± 3.4% (P < .001) in hypercholesterolemic mice treated with paraquat. CONCLUSION: Re-endothelialization of arterial injuries is reduced in hypercholesterolemic mice and is inversely correlated with oxidative stress. An oral antioxidant decreases oxidative stress and improves EC healing. CLINICAL RELEVANCE: Vascular injury following cardiovascular intervention, including cardiac and peripheral arterial angioplasty and stenting, is associated with inflammation and oxidative stress. Hypercholesterolemia is also associated with increased oxidative stress. Oxidative stress, regardless of the source, induces cellular dysfunction in endothelial and smooth muscle cells that reduce healing after arterial injury. Decreasing oxidative stress with an exogenously administered antioxidant can improve endothelial cell healing, and this is important to control intimal hyperplasia and reduce the thrombogenicity of the vessel.

Epigenetic silencing of the sulfate transporter gene DTDST induces sialyl Lewisx expression and accelerates proliferation of colon cancer cells.

Colon cancer cells express the carbohydrate determinant sialyl Lewis(x), while they exhibit markedly decreased the expression of its sulfated derivative, sialyl 6-sulfo Lewis(x). In contrast, normal colonic epithelial cells strongly express sialyl 6-sulfo Lewis(x), but they virtually do not express sialyl Lewis(x). Impaired sulfation was therefore suggested to occur during the course of malignant transformation of colonic epithelial cells and was assumed to be responsible for the increased sialyl Lewis(x) expression in cancers. To elucidate the molecular biological background of the impaired sulfation in cancers, we studied the expression levels of mRNA for 6-O-sulfotransferase isoenzymes, PAPS synthases and transporters, and a cell membrane sulfate transporter, DTDST, in cancer tissues. The most striking decrease in cancer cells compared with nonmalignant epithelial cells was noted in the transcription of the DTDST gene (P = 0.0000014; n = 20). Most cultured colon cancer cells had a diminished DTDST transcription, which was restored when cultured with histone deacetylase inhibitors. Suppression of DTDST transcription under the control of a tet-off inducible promoter resulted in increased sialyl Lewis(x) expression and reduced sialyl 6-sulfo Lewis(x) expression. Unexpectedly, the growth rate of the cancer cells was markedly enhanced when transcription of DTDST was suppressed. These results show that the decrease in the transcription of the sulfate transporter gene is the major cause of decreased expression of sialyl 6-sulfo Lewis(x) and increased expression of sialyl Lewis(x) in colon cancers. The results also suggest that the diminished DTDST expression is closely related to enhanced proliferation of cancer cells.

Altered expression of glycan genes in cancers induced by epigenetic silencing and tumor hypoxia: clues in the ongoing search for new tumor markers.

The glycan molecules that preferentially appear in cancers are clinically utilized as serum tumor markers. The exact reason, however, why glycans are useful as tumor markers remain elusive. Here, we will summarize lessons learned from well-established cancer-associated glycans, and propose strategies to develop new cancer markers. Our recent results on cancer-associated glycans, sialyl Lewis A and sialyl Lewis X, indicated that the repressed transcription of some glycan genes by epigenetic silencing during early carcinogenesis, and the transcriptional induction of some other glycan genes by tumor hypoxia accompanying cancer progression at locally advanced stages, are two major factors determining cancer-associated glycan expression. Multiple genes are involved in glycan synthesis, and epigenetic silencing of a part of such genes leads to accumulation of glycans having truncated incomplete structures, which are readily detected by specific antibodies. Glycans are very unique and advantageous as marker molecules because they are capable of reflecting epigenetic silencing in their structures. Transcriptional induction of some glycan genes by tumor hypoxia at the later stages produces further glycan modifications, such as an unusual increase of the N-glycolyl sialic acid residues in the glycan molecules. The entire process of malignant transformation thus creates abnormal glycans, whose structures reveal the effects of both epigenetic silencing and tumor hypoxia. The second advantage of a glycan marker over a proteinous marker is that they can reflect the plurality of genetic anomalies in a singular molecule, as it is synthesized by the cooperative action of multiple genes. Glycans are sometimes covalently bound to well-known cancer-associated proteins, such as CD44v, and this eventually contributes to a high cancer specificity and functional relevancy in cancer progression.

Altered sphingolipid metabolism induced by tumor hypoxia - new vistas in glycolipid tumor markers.

Uncontrolled growth of malignant cells produces hypoxic regions in locally advanced tumors. Recently we showed that tumor hypoxia-induced transcription of multiple genes involved in glycan synthesis, leading to expression of useful glycolipid tumor markers, such as gangliosides having N-glycolyl sialic acid. Our subsequent studies indicated that the ceramide portion of glycolipids, as well as their glycan moiety, was also significantly affected by hypoxia. Tumor hypoxia-induced marked accumulation of sphinganine (dihydrosphingosine) long-chain base, and significant reduction of unsaturated very long-chain fatty acids in the ceramide moiety. Mass-spectrometry, which yields information on both glycan- and ceramide moieties, is expected to be clinically useful in detecting such distinct molecular species of cancer-associated glycolipids having combined alteration in both glycan- and ceramide moieties.

Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits.

OBJECTIVE: Limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased EC migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing in hypercholesterolemic animals. METHODS: Rabbits were placed in one of four groups: chow plus N-acetylcysteine (NAC), chow plus probucol, chow with 1% cholesterol plus NAC, or chow with 1% cholesterol plus probucol. After 2 weeks, expanded polytetrafluoroethylene grafts (12 cm long x 4-mm internal diameter) were implanted in the abdominal aorta. Grafts were removed after 6 weeks and analyzed for cholesterol content, EC coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress. The data were compared with previously reported data from animals fed diets of chow and chow with 1% cholesterol. RESULTS: Prosthetic grafts from rabbits fed chow with 1% cholesterol had significantly greater anastomotic intimal thickening and lower EC coverage than grafts from rabbits fed a regular chow diet. In hypercholesterolemic rabbits, antioxidant therapy decreased global oxidative stress as evidenced by a 40% decrease in plasma thiobarbituric acid reactive substances. In rabbits fed the chow with 1% cholesterol diet, NAC decreased intimal hyperplasia at the proximal anastomosis by 29% and significantly increased graft EC coverage from 46% to 71% (P = .03). Following a similar pattern, probucol decreased intimal hyperplasia by 43% and increased graft EC coverage to 53% in hypercholesterolemic rabbits. CONCLUSIONS: Global oxidative stress and anastomotic intimal hyperplasia are increased, and endothelialization of prosthetic grafts is significantly reduced in rabbits fed a high-cholesterol diet. Antioxidant treatment improves EC coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote healing of prosthetic grafts.

Optimizing functional parameter accuracy for breath-hold DCE-MRI of liver tumours.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a valuable tool for assessing treatment response to novel cancer therapeutics. With appropriate data acquisition, quantitative functional parameter estimates can be obtained by fitting a model to the data. This research focuses on applying a dual-input single-compartment pharmacokinetic model to breath-hold DCE-MRI imaging of the liver. In this paper, the use of two breath-holds, providing greater temporal information, is compared with a single breath-hold approach. Computer simulations are used to assess the accuracy, precision and sensitivity to input function errors obtained for parameters estimated from the two imaging protocols. Data from ten patients were analysed to assess the noise statistics obtained from the two breath-hold protocols. The noise statistics were used with a pharmacokinetic liver model to simulate data, from which the estimation accuracy, precision and sensitivity for the two protocols were assessed. Data from the ten patients were also analysed, and the estimates were compared with literature values. This work demonstrates the feasibility of obtaining functional liver perfusion estimates over a 3D volume using a sequential breath-hold protocol. The simulation results show that the protocol consisting of two images per breath-hold is to be preferred as it requires identical patient co-operation, but provides parameter estimates that have superior accuracy and precision.

Cilostazol suppresses neointimal hyperplasia in canine vein grafts.

PURPOSE: To investigate whether cilostazol, a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, suppresses intimal hyperplasia in canine vein grafts, and to elucidate its mechanisms in terms of cell proliferation and apoptosis. METHODS: Bilateral reversed jugular vein interposition grafts of the common carotid artery were performed in 12 beagle dogs. Starting from 7 days before surgery, either cilostazol (30 mg/day; n = 6) or a placebo (n = 6) was given orally twice daily. Vein grafts were harvested at 1 or 4 weeks, and fixed under pressure for histological examination. RESULTS: By 1 week after implantation, the cilostazol group showed significantly less cell proliferation than the placebo group. By 4 weeks after implantation, intimal and medial thickness was significantly thinner in the cilostazol group than in the placebo group. There was significantly more apoptosis in the placebo group than in the cilostazol group at both time points. CONCLUSION: Cilostazol suppressed the development of intimal hyperplasia in canine autogenous vein grafts. Thus, it may be associated with the modulation of cell proliferation and apoptosis.