Olive leaf tea may have hematological health benefit over green tea.

Olive leaf extracts are rich in several polyphenols having potential health benefits. We conducted the current parallel-group randomized controlled trial to compare the effects of long-term consumption of olive leaf tea (OLT) and green tea (GT) on hematological parameters in 31 female volunteers aged between 40 and 70 years of old. We found that RBC count, hemoglobin, and hematocrit were increased significantly in the OLT group than those of in the GT group at 6 and 12 weeks of intervention. Within-group comparison showed that hematocrit was significantly increased in the OLT group at 6 weeks of intervention, whereas RBC count and serum iron was significantly decreased in the GT group at 12 weeks of intervention. This is the first clinical study reporting the beneficial effects of continuous intake of OLT on hematological parameters. This observation is supported by our previous in vitro study reporting the differentiation-inducing effect of certain olive leaf components on human hematopoietic stem cells. However, further investigations in larger cohorts with a careful consideration of target population are required to confirm the preventive effect of OLT against anemia and other red cell disorders.

A Multiple-Cell Microenvironment in a 3-Dimensional System Enhances Direct Cellular Reprogramming Into Hepatic Organoids.

OBJECTIVES: The difficulty in proliferation and availability and the rapid loss functions of primary human hepatocytes highlight the need to develop an alternative, preferably renewable source of human induced hepatocytes in regenerative medicine. Liver organoids generated on a multiple-cell microenvironment in a 3-dimensional (3D) system can provide a highly efficient solution to this issue. METHODS: Human hepatocytes were induced from fibroblasts by the lentiviral expression of FOXA3, HNF1A, and HNF4A. Together with these induced hepatocytes, human umbilical vein endothelial cells and mesenchymal stem cells in a 3D system were used to produce liver organoids. Liver-related gene and protein expression of liver organoids and induced hepatocytes were tested using a 2-dimensional (2D) system. RESULTS: Liver organoids notably increased the expression of hepatic transcription factors, marker genes, transporter genes, and liver metabolism enzyme genes, while it decreased the specific gene expression of fibroblasts. Liver organoids expressed comparable liver-specific proteins, such as ALB, AAT, and HNF4A in the 3D system. CONCLUSION: Direct reprogramming in multiple-cell microenvironments in 3D systems is more controllable and efficient than cell reprogramming in 2D systems. Liver organoids have the potential for use in disease modeling, pharmaceutical applications, and cellular transplantation.

Quantitative Analysis of Conebeam CT for Delineating Stents in Stent-Assisted Coil Embolization.

BACKGROUND AND PURPOSE: Innovative techniques and device-related advances have improved the outcomes of neuroendovascular treatment. 3D imaging has previously used 2 × 2 binning, but 1 × 1 binning has recently been made available. The aim of this study was to evaluate the quantitative ability of conebeam CT for stent delineation and to investigate its effectiveness in the clinical environment. MATERIALS AND METHODS: Four acquisition groups of 3D MIP images acquired using conebeam CT with varying conditions (acquisition time, 10 or 20 seconds and binning, 1 × 1 or 2 × 2) were compared. Two methods of analysis were performed, a phantom study and an analysis of 28 randomly selected patients. The phantom study assessed the contrast-to-noise ratio and full width at half maximum values in conebeam CT images of intracranial stent struts. In the clinical subjects, we assessed contrast-to-noise ratio, full width at half maximum, and dose-area product. RESULTS: In the phantom study, the contrast-to-noise ratio was not considerably different between 10- and 20-second acquisition times at equivalent binning settings. Additionally, the contrast-to-noise ratio at equivalent acquisition times did not differ considerably by binning setting. For the full width at half maximum results, equivalent acquisition times differed significantly by binning setting. In the clinical analyses, the 10-second/1 × 1 group (versus 20 second/2 × 2) showed a higher contrast-to-noise ratio (P < .05) and a dose-area product reduced by approximately 70% (P < .05), but the difference in full width at half maximum was not significant (P = .20). CONCLUSIONS: For stent-assisted coil embolization, quantitative assessment of conebeam CT showed that 10 second/1 × 1 was equivalent to 20 second/2 × 2 for imaging deployed intracranial stents. Furthermore, the 10-second/1 × 1 settings resulted in a much smaller DAP.

Hemodynamic assessment of celiaco-mesenteric anastomosis in patients with pancreaticoduodenal artery aneurysm concomitant with celiac artery occlusion using flow-sensitive four-dimensional magnetic resonance imaging.

OBJECTIVES: Many pancreaticoduodenal artery (PDA) aneurysms are associated with celiac artery (CA) stenosis. The pathogenesis of PDA aneurysm may be associated with hemodynamic changes due to CA stenosis/occlusion. The aim of this study was to assess the hemodynamic changes of celiaco-mesenteric anastomosis in patients with PDA aneurysms concomitant with CA occlusion using four-dimensional flow-sensitive magnetic resonance imaging (4D-Flow). METHODS: 4D-Flow was performed preoperatively on five patients. Seven age- and sex-matched individuals were used as controls. Hemodynamic parameters such as flow volume and maximum flow velocity in PDAs, gastroduodenal arteries, common hepatic arteries, and superior mesenteric arteries were compared between both groups. Wall shear stress (WSS) and oscillatory shear index (OSI) were mapped in both groups. RESULTS: In the patient group, 4D-Flow identified retrograde flow of both gastroduodenal arteries and common hepatic arteries. Heterogeneous distribution patterns of both WSS and OSI were identified across the entire PDA in the patient group. OSI mapping showed multiple regions with extremely high OSI values (OSI > 0.3) in all patients. All PDA aneurysms, which were surgically resected, were atherosclerotic. CONCLUSIONS: 4D-Flow identified hemodynamic changes in celiaco-mesenteric arteries in patients with PDA aneurysms with concomitant CA occlusion. These hemodynamic changes may be associated with PDA aneurysm formation.

Accurate determination of patient-specific boundary conditions in computational vascular hemodynamics using 3D cine phase-contrast MRI.

In the patient-specific vascular CFD, determination of the inlet and outlet boundary conditions (BCs) is an important issue for a valid diagnosis. The 3D cine phase-contrast MRI (4D Flow) velocimetry is promising for this issue; yet, its measured velocities contain relatively large error and are not admissible as the BCs without any correction. This paper proposes a novel correction method for determining the BCs accurately using the 4D Flow velocimetry. First, we reveal that the error of the velocity measured by the 4D Flow at each measurement voxel is large but is distributed symmetrically. Secondly, our method pays attention to the incompressibility of the blood and the fact that the volume flow rate (VFR) in each vessel is constant on any cross sections. We reveal that the average of the cross-sectional VFRs integrated from many measurement voxel in each vessel is accurate despite the large error. Finally, we propose the novel correction method, which applies a smoothing to the measured velocities on each inlet or outlet boundary with a low-pass filter and then corrects them with the VFR. The results of the several phantom studies are presented to validate the accuracy of our method. A demonstrative analysis for an actual aneurysm is also presented to show the feasibility and effectiveness of our method.

An automated rapid detection system using the quenching probe method for detecting interleukin 28B and inosine triphosphatase single nucleotide polymorphisms in chronic hepatitis C.

Single nucleotide polymorphisms (SNPs) in the interleukin 28B gene (IL28B) are good pretreatment predictors of anti-hepatitis C virus (HCV) therapy with interferon. SNPs of the inosine triphosphatase (ITPA) gene are associated with reduced haemoglobin levels during treatment with ribavirin. The i-densy™ (Arkray, Inc.), which is based on the quenching probe (QP) method, automatically detects target genes in blood samples by fluorescence quenching within 100 min. Using a QP and primer set, a gene amplification response is generated that can quickly and easily detect a specific gene's arrangement by fluorometry. The present study was conducted to compare the utility of i-densy (QP method) with that of conventional direct sequencing (DS) for detecting SNPs in the IL28B and ITPA genes in chronic hepatitis C patients. Between June 2011 and January 2012, 73 consecutive patients underwent genotyping of IL28B, and 54 patients underwent genotyping of ITPA. All of the patients were seropositive for HCV-RNA. The IL28B and ITPA genotypes were tested for bi-allelic polymorphisms in rs8099917 (T/T, T/G and G/G; minor allele, G) and rs1127354 (C/C, C/A and A/A; minor allele, A), respectively. The results obtained with the QP method were identical to those obtained with the conventional DS method. The frequency of the IL28B genotypes TT, GT and GG were 74%, 24.7% and 1.4%, respectively, and those of the ITPA genotypes CC, AC and AA were 68.5%, 29.6% and 1.9%, respectively. These results indicate that the i-densy using the QP method can automatically, quickly and easily identify genotypes of IL28B and ITPA.

Assessment of wastewater-irrigated soil containing heavy metals and establishment of specific biomarkers.

Irrigation with treated wastewater (TWW) is a vital alternative for arid and semi-arid lands but it poses pollution-risk to soil, vegetation and groundwater. Therefore, in the present study, in vitro bioassays were used to evaluate the adverse effects of TWW and irrigated-soil extract sample, on mammalian cells, with respect to heavy metal--Ni, Cd, Pb, Fe, Al-content. The heat shock protein (HSP) 47, E-screen, and transepithelial electrical resistance (TEER) assays served to investigate the stress response of treated-HSP47-transfected Chinese hamster ovary (CHO) cells, the estrogenic activity of the samples in MCF-7 breast cancer cells, and the barrier function (BF) of Caco-2 cells. Furthermore, proteomics analyses were performed to shed light on involved mechanisms and to establish pollution biomarkers. Results showed that the TWW elicited a stress response on HSP cells from 0.1% concentration while soil extract samples exhibited a stress at 1%. TWW induced an estrogenic activity at 10%; up-regulating cell proliferation and tumor-related proteins. Soil extract triggered the enhanced expression of HSP70 family proteins as survival mechanisms against their cytotoxicity toward MCF-7 cells. Moreover, depending on the concentration, 1% of soil extract from 20 cm depth (T20) resulted in a disruption of BF in Caco-2 cells involving cell metabolism, protein synthesis and tumor marker proteins, whereas, 5% of T20 induced the expression of BF-related proteins associated to heat shock, oxidative stress, cell proliferation and glycolytic metabolic pathway. These biological techniques were found to be extremely useful to evaluate the impact of wastewater reuse and to establish specific biomarkers that are common proteins for humans, other mammals and plants. Future studies should focus on exposure quantifications.

Uptake of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid in metastatic adrenal tumour from hepatocellular carcinoma.

We present the case of a metastatic adrenal tumour from hepatocellular carcinoma (HCC) showing the uptake of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) on MRI. To our knowledge, this is the first case of metastatic HCC in which Gd-EOB-DTPA uptake was shown on MRI and this finding facilitated the accurate pre-operative diagnosis of a metastatic adrenal tumour.

Neuroprotective effect of 3,5-di-O-caffeoylquinic acid on SH-SY5Y cells and senescence-accelerated-prone mice 8 through the up-regulation of phosphoglycerate kinase-1.

As aged population dramatically increases in these decades, efforts should be made on the intervention for curing age-associated neurologic degenerative diseases such as Alzheimer's disease (AD). Caffeoylquinic acid (CQA), an antioxidant component and its derivatives are natural functional compounds isolated from a variety of plants. In this study, we determined the neuroprotective effect of 3,5-di-O-CQA on Abeta(1-42) treated SH-SY5Y cells using MTT assay. To investigate the possible neuroprotective mechanism of 3,5-di-O-CQA, we performed proteomics analysis, real-time PCR analysis and measurement of the intracellular ATP level. In addition, we carried out the measurement of escape latency time to find the hidden platform in Morris water maze (MWM), real-time PCR using senescence-accelerated-prone mice (SAMP) 8 and senescence-accelerated-resistant mice (SAMR) 1 mice. Results showed that 3,5-di-O-CQA had neuroprotective effect on Abeta (1-42) treated cells. The mRNA expression of glycolytic enzyme (phosphoglycerate kinase-1; PGK1) and intracellular ATP level were increased in 3,5-di-O-CQA treated SH-SY5Y cells. We also found that 3,5-di-O-CQA administration induced the improvement of spatial learning and memory on SAMP8 mice, and the overexpression of PGK1 mRNA. These findings suggest that 3,5-di-O-CQA has a neuroprotective effect on neuron through the upregulation of PGK1 expression and ATP production activation.

Inhibitory effect of various Tunisian olive oils on chemical mediator release and cytokine production by basophilic cells.

Tunisian olive oils have been traditionally used as a medicinal food for chronic inflammation. To investigate the antiallergic effect of virgin olive oil samples from five principal olive varieties grown in various regions of Tunisia, we used the type I allergy reaction model using rat basophilic leukemia (RBL-2H3) cells and different dilutions of olive oil samples to determine beta-hexosaminidase release inhibition at two different response stages. Results showed that the Sayali olive oil significantly inhibited beta-hexosaminidase release by the IgE antibody-sensitized, BSA antigen-stimulated RBL-2H3 cells at the antibody-antigen binding stage. The result of our experiment shows that the anti-allergic effect of olive oil at this binding stage may be dependent on their flavone content. The Zarrazi olive oil significantly inhibited beta-hexosaminidase release at the antigen-receptor binding stage. Moreover, we investigated the effect of olive oil samples on histamine release and production of cytokines by activated human basophilic (KU812) cells. Different dilutions of Sayali olive oil dose-dependently inhibited the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4), and different dilutions of Zarrazi olive oil dose-dependently inhibited histamine release and IL-4 production by calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (PMA)-stimulated KU812 cells.

Visualization of hemodynamics in a silicon aneurysm model using time-resolved, 3D, phase-contrast MRI.

We performed time-resolved 3D phase-contrast MR imaging by using a 1.5T MR scanner to visualize hemodynamics in a silicon vascular model with a middle cerebral aneurysm. We ran an aqueous solution of glycerol as a flowing fluid with a pulsatile pump. Time-resolved images of 3D streamlines and 2D velocity vector fields clearly demonstrated that the aneurysm had 3D complex vortex flows within it during systolic phase. This technique provided us with time-resolved 3D hemodynamic information about the intracranial aneurysm.

Expressions of galectin-3, glutathione S-transferase A2 and peroxiredoxin-1 by nonylphenol-incubated Caco-2 cells and reduction in transepithelial electrical resistance by nonylphenol.

Nonylphenol, an estrogenic xenobiotic widely used in the manufacture of plastics and detergents, has been found in drinking water and may therefore enter the body through the oral route. Thus, intestinal cells lining the alimentary tract serve as the body's first line of defense against this compound. In this study, the effects of nonylphenol on the human intestinal cell line Caco-2 were determined using transepithelial electrical resistance (TEER) measurement and proteomics. Results show that 10 microM nonylphenol can disrupt the tight-junction permeability of Caco-2 cells in approximately 15 min. Incubating the cells with 1 or 10 microM nonylphenol for 6 days resulted in the enhanced expressions of galectin-3 (approximately 4-fold vs. control with 1 microM; 2-fold with 10 microM), glutathione S-transferase A2 (approximately 8-fold with 1 microM; 5-fold with 10 microM) and peroxiredoxin-1 (approximately 6-fold with 1 microM; 4-fold with 10 microM). These expressions may represent a possible consortium of mechanisms by which the cells protect themselves against nonylphenol-induced stresses. To the best of our knowledge, this is the first study on the effects of nonylphenol on Caco-2 cells.

In-Vitro Simulation of NBCA Embolization for Arteriovenous Malformation.

SUMMARY: Embolization using n-butyl-cyanoacrylate (NBCA) for arteriovenous malformation (AVM) is now a daily practice over the world, but there exists no objective data that can be a basis for discussion or decision-making on the best concentration and injection rate of NBCA mixture. The purpose of this study was to obtain objective data on control and behavior of NBCA mixture with an in vitro simulation system of NBCA embolization for AVM. A nidus model made of a one-ml syringe filled with small beads was connected to a pulsatile flow circuit. A microcatheter was introduced just before the nidus model. Endoluminal pressures proximal and distal to the nidus and flow volume through the nidus were measured. Digital subtraction angiography (DSA) was performed to calculate transit time of the contrast medium (CM) through the nidus. NBCA was injected at various rates with an autoinjector and transit time of NBCA through the nidus was calculated. 27 trials were completed. Transit time of CM through the nidus model is well correlated to flow volume per unit of time through the nidus model. Shorter the transit time, larger was the flow volume per unit of time. The correlation was statistically significant (P < .0001). Though statistical significance was not attained, transit time of NBCA mixture at 50% concentration had a tendency to be correlated to flow volume per unit of time through the nidus, and slower injection of the NBCA mixture led to slower filling of the nidus model. Though this simulation system was artificial and the results should be interpreted carefully, it was shown with this system that transit time of CM through the nidus could be a good index for flow volume per unit of time through the nidus. Also suggested was a possibility to utilize this in vitro system for research and training on NBCA embolization of AVM.

Fibroma of the vulva.

We describe a patient with fibroma of the vulva. The tumor had areas of marked hypointensity consistent with fibrosis on T1 and T2 weighted magnetic resonance (MR) images. The presence of abundant fibrous tissues on MR images enabled us to make a preoperative diagnosis of fibroma.

Dynamic gadolinium-enhanced MR imaging of pituitary adenomas: usefulness of sequential sagittal and coronal plane images.

Dynamic magnetic resonance (MR) imaging for pituitary adenomas is usually performed in a coronal direction; however, small lesions between slices, or lesions located at the anterior or posterior aspect of the pituitary gland might be overlooked on MR images in only the coronal direction. The purpose of our study was to evaluate whether consecutive dynamic MR images in the coronal and sagittal planes improve detection of pituitary adenomas. Eighteen patients with pituitary microadenomas and nine with healthy pituitary glands were included in this study. MR images were performed with 1.5 T superconductive units and commercially-available head coils. After a 5 ml gadolinium contrast injection, eight serial dynamic sagittal images were obtained. Within 3 or 6 min, this was followed by a 10-15 ml gadolinium injection and acquisition of eight serial dynamic coronal images. Dynamic MR images and conventional noncontrast- and contrast-enhanced sagittal and coronal T1-weighted images were evaluated independently in a blind fashion by two neuroradiologists regarding the depiction of pituitary microadenomas. The sensitivities of dynamic enhanced MR imaging in the detection of microadenomas were 61.1% in sagittal direction, 72.2% in coronal direction respectively, and were superior to those of conventional noncontrast- and contrast-enhanced T1-weighted imaging (22.2-50%). The sensitivity of a combination of sagittal and coronal dynamic enhanced MR imaging for the detection of microadenomas was 88.9% and was superior to those of conventional noncontrast- and contrast-enhanced T1-weighted imaging combining sagittal and coronal directions (61.1%, 61.1%) (P<0.05, P<0.05, respectively). The specificity and accuracy of dynamic enhanced MR imaging with combination of sagittal and coronal images was 88.9% respectively. Dynamic gadolinium-enhanced MR imaging, especially using both sagittal and coronal planes, was concluded to be useful for the detection of pituitary microadenomas.

Multiple myeloma: short T2 on MR imaging.

We describe a rare case of multiple myeloma with marked hypointense areas on both T1- and T2-weighted images. Amyloid deposition and calcification were not found histologically. Hypointensity on T2-weighted images may be caused by distributed free radicals produced by significant macrophages.