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Sample records for initial microvessel density

  1. Microvessel and astroglial cell densities in the mouse hippocampus.

    PubMed Central

    Shimada, M; Akagi, N; Goto, H; Watanabe, H; Nakanishi, M; Hirose, Y; Watanabe, M

    1992-01-01

    In order to study the factors responsible for glucose uptake in the mouse hippocampus, microvessel and astroglial cell densities were measured and compared in each laminal region. Microvessel density was examined on histologically prepared sections after injection of Indian ink and measured by means of an image analyser. Astroglial cell density was determined after the cells were stained immunohistochemically. Microvessel and astroglial cell densities were determined in 10 different hippocampal structures. Microvessel and astroglial cell densities were strongly correlated in all layers except the pyramidal cell layers. The highest density of perfused microvessels was found in the stratum lacunosum-moleculare, compared with other regions, and the lowest values were found in the stratum lucidum and dentate granular cell layer. Among pyramidal cell layers, microvessel density in sector CA3a was significantly higher than that in CA1. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1452486

  2. Augmented mast cell infiltration and microvessel density in prostate cancer

    PubMed Central

    Wagrowska-Danilewicz, Małgorzata; Stasikowska-Kanicka, Olga; Tuka, Elżbieta; Danilewicz, Marian

    2013-01-01

    Aim of the study Recent investigations have taken into account the role of mast cells in prostate cancer formation, analyzing their dual functions (as tumour growth promoters and tumour growth inhibitors). The aim of our study was to compare mast cell infiltration and microvessel density in prostate cancer and in benign prostate hyperplasia. We also attempted to find possible relationships among mast cell infiltration and microvessel density, Gleason score, as well as serum levels of prostate-specific antigen (PSA). Material and methods The investigation was confined to evaluations of material from prostate needle biopsies, carried out in 26 patients with prostate cancer, and of 14 specimens diagnosed as benign hyperplasia. The numbers of tryptase positive mast cells and CD34 positive vessels were determined using a computer image analysis system. In the patients with prostate cancer, both mast cell infiltrates and microvessel density were significantly increased, as compared to the control patients. Results Significant positive correlations were identified between the mean numbers of mast cells and microvessel densities, both in the prostate cancer group and in the control group. Moreover, significant positive correlations were observed between Gleason score on one hand and the number of mast cells and microvessel density on the other. The correlations between PSA serum levels and both mast cell infiltration and microvessel density were positive, but not in a statistically significant way. Conclusions The reported investigations may support the assumption of mast cell promoter function in prostate cancer development, whereas no evidence was found for their opposite PMID:24592126

  3. Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

    PubMed Central

    Jureidini, Ricardo; da Cunha, José Eduardo Monteiro; Takeda, Flavio; Namur, Guilherme Naccache; Ribeiro, Thiago Costa; Patzina, Rosely; Figueira, Estela RR; Ribeiro, Ulysses; Bacchella, Telesforo; Cecconello, Ivan

    2016-01-01

    OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma. PMID:27438564

  4. Does the patients age at cancer diagnosis affect microvessels density in uterine sarcoma tissues?

    PubMed

    Bobiński, Marcin; Bednarek, Wiesława; Okła, Karolina; Polak, Grzegorz; Sobstyl, Małgorzata; Wertel, Iwona; Kotarski, Jan

    2017-01-01

    The objective of the study was to retrospectively evaluate the density of vessels exhibiting positive glycoprotein CD34 expression in the uterine leiomyosarcoma tissues and their correlation with the age of patients at the time of tumor diagnosis. The archival paraffin blocks with the cancer tissues collected from 50 patients suffering from uterine leiomyosarcoma were used together with their clinical and demographic data. The immunohistochemical peroxidase-de-pendent methods were used to detect microvessels with positive CD34 expression. The glycoprotein CD34 expression was evaluated as a density of microvessel showing the positive immunohistochemical reaction (MVDCD34). The negative, statistically significant correlation between the age of patients (at the moment diagnosis) and the MVDCD34+ (R = -0.289, p = 0.042) was found. The study's findings may suggest that the tissues of younger people constitute a permissive environment for pro-angiogenic factors.

  5. Vascular endothelial growth factor and intratumoral microvessel density as prognostic factors in endometrial cancer.

    PubMed

    Topolovec, Zlatko; Corusić, Ante; Babić, Damir; Mrcela, Milanka; Sijanović, Sinisa; Müller-Vranjes, Andrijana; Curzik, Darko

    2010-06-01

    The aim of this research was to determine the VEGF A expression in tumor cells and the intratumoral microvessel density and their prognostic significance in the survival of the subjects. 87 subjects were monitored retrospectively for a period of 60 to 132 months. The subjects were treated at the Department of Obstetrics and Gynecology of Osijek University Hospital Center, Croatia. We analysed standard clinical, pathohistological and therapeutical prognostic factors, intratumoral microvessel density and expression of VEGF A. Five-year survival was calculated by the life chart method and presented graphically by Kaplan-Meier curves. Reaching conclusions on statistical hypotheses in this paper was done with a reliability level p < 0.05. Of the analyzed clinical prognostic factors, those which proved to be statistically significant and independent prognostic factors were age and clinical stage of the disease, and of pathohistologic ones it was the depth of myometrial invasion and VEGF expression. An elevated VEGF expression is associated with deep myometrial invasion, poorly differentiated tumors, histologic type and intratumoral microvessel density to a statistically significant degree. Elevated VEGF expression, age, FIGO stage and depth of myometrial invasion play a significant prognostic role in patients with endometrial cancer. VEGF receptors could be a target for adjuvant therapy in VEGF positive endometrial cancer.

  6. Engineered Microvessels with Strong Alignment and High Lumen Density Via Cell-Induced Fibrin Gel Compaction and Interstitial Flow

    PubMed Central

    Morin, Kristen T.; Dries-Devlin, Jessica L.

    2014-01-01

    The development of engineered microvessels with clinically relevant characteristics is a critical step toward the creation of engineered myocardium. Alignment is one such characteristic that must be achieved, as it both mimics native capillary beds and provides natural inlet and outlet sides for perfusion. A second characteristic that is currently deficient is cross-sectional lumen density, typically under 100 lumens/mm2; the equivalent value for human myocardium is 2000 lumens/mm2. Therefore, this study examined the effects of gel compaction and interstitial flow on microvessel alignment and lumen density. Strong microvessel alignment was achieved via mechanically constrained cell-induced fibrin gel compaction following vasculogenesis, and high lumen density (650 lumens/mm2) was achieved by the subsequent application of low levels of interstitial flow. Low interstitial flow also conferred microvessel barrier function. PMID:24083839

  7. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  8. Reconsideration of the clinical and histopathological significance of angiogenesis in prostate cancer: Usefulness and limitations of microvessel density measurement.

    PubMed

    Miyata, Yasuyoshi; Sakai, Hideki

    2015-09-01

    Angiogenesis plays important roles in tumor growth and cancer cell dissemination in almost all cancers. In prostate cancer, there is general agreement that increased angiogenesis is an important factor in determining tumor development and prognosis in these patients. Microvessel density is recognized as a useful marker for evaluating the angiogenic status of cancer tissues. Many investigators have reported that microvessel density is significantly associated with pathological features and outcomes in prostate cancer patients; however, some researchers have expressed opposing opinions. As the reason for such discrepancy, previous reports have suggested differences in the methodologies of measuring microvessel density in cancer tissues. In the present review, we focus on the variation in such methods, including the selected area and the method used for (semi)quantification. In particular, we discuss the relationship between malignancy potential, tumor progression, and survival and differences in the antibodies used for detection of endothelial cells in detail. We briefly compare the pathological significance and prognostic roles of microvessel density measured using von Willebrand factor, CD31, CD34, and CD105. Based on these analyses, the advantages and limitations of microvessel density measurements in prostate cancer tissues are clarified. Improved "real" and "specific" markers of cancer-related angiogenesis are necessary for better predictions of prognoses and for discussion of treatment strategies for patients with prostate cancer. However, establishment of a satisfactory cancer-related endothelial marker could take a long time. Therefore, knowledge regarding the pathological significance of microvessel density - based on understanding of the advantages and limitations of microvessel density determination methods - is important.

  9. Variability in sublingual microvessel density and flow measurements in healthy volunteers.

    PubMed

    Hubble, Sheena M A; Kyte, Hayley L; Gooding, Kim; Shore, Angela C

    2009-02-01

    As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. Measurements of sublingual capillary density and flow were obtained by recording three 15-second images in 20 healthy volunteers over three days. Two independent observers quantified capillary density by using two methods: total vessel length (mm/mm2) and counting (number/mm). Both intraoral and temporal variabilities within subject and observer reproducibilities were determined by using coefficients of variability and reproducibility indices. For small (1-10 microm), medium (11-20 microm), and large (21-50 microm) diameter, mean vessel density with standard deviations (SDs) in volunteers was 21.3(+/- 4.9), 5.2 (+/- 1.2), and 2.7 (+/- 0.9) mm/mm2, respectively. Also, 94.0 +/- 1.4% of small vessels, 94.5 +/- 1.4% of medium vessels, and 94.5+/- 4.0% of large vessels had continuous perfusion. Within subjects, the means of all measurements over three days varied less than 13, 22, and 35% in small, medium, and large vessels, respectively. Interobserver reproducibility was good, especially for capillary (1-10 microm) density and flow measurements. Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.

  10. Microvessel density and p53 mutations in advanced-stage epithelial ovarian cancer.

    PubMed

    Nadkarni, Niyati J; Geest, Koen De; Neff, Traci; Young, Barry De; Bender, David P; Ahmed, Amina; Smith, Brian J; Button, Anna; Goodheart, Michael J

    2013-04-30

    We planned to determine the relationship between angiogenesis and p53 mutational status in advanced-stage epithelial ovarian cancer. Using 190 tumor samples from patients with stage III and IV ovarian cancer we performed p53 sequencing, immunohistochemistry, and CD31 microvessel density (MVD) determination. MVD was elevated in tumors with p53 null mutations compared to p53 missense mutation or no mutation. Disease recurrence was increased with higher MVD in both unadjusted and adjusted analyses. In adjusted analysis, p53 null mutation was associated with increased recurrence and worse overall survival. Worse overall survival and increased recurrence risk were also associated with the combination of CD31 MVD values >25 vessels/HPF and any p53 mutation. P53 mutation status and MVD may have prognostic significance in patients with advanced-stage ovarian cancer. Tumors with p53 null mutations are likely to be more vascular, contributing to decreased survival and increased recurrence probability.

  11. Involvement of mast cells and microvessels density in reactive lesions of oral cavity: A comparative immunohistochemical study.

    PubMed

    Ferreira, Stephany Vasco; Xavier, Flávia Caló Aquino; Freitas, Maria da Conceição Andrade de; Nunes, Fábio Daumas; Gurgel, Clarissa Araújo; Cangussu, Maria Cristina Teixeira; Martins, Manoela Domingues; Freitas, Valéria Souza; Dos Santos, Jean Nunes

    2016-09-01

    In view of the similarity of clinicopathological features between reactive lesions of the oral cavity, the objective of the present study was to investigate the density of MCs (mast cells) and microvessels in a series of these lesions. Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10), inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL, n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using immunohistochemistry for mast cell tryptase and CD34. For comparative purposes, central giant cell lesions (CGCL, n=5) were included. A higher MC density was observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There was a significant difference in MC density when all reactive lesions were compared to CGCL (p=0.001). The largest mean density of microvessels was observed in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a significant difference in microvessel density when the reactive lesions were compared to CGCL (p=0.003). There was a significant and direct correlation between the density of MCs and microvessels only for IFH (p=0.048) and CGCL (p=0.005). A significant and direct correlation between the mean density of MCs and microvessels was observed when the reactive lesions were analyzed as a whole (p=0.005). Our results suggest that mast cells contribute to the connective tissue framework and angiogenic function, as well as the development, of reactive lesions of the oral cavity, including FH, IFH, LCH and PGCL. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Microvessel density and Ki-67 labeling index in esthesioneuroblastoma: is there a prognostic role?

    PubMed

    Singh, Lavleen; Ranjan, Richa; Madan, Renu; Arava, Sudheer K; Deepak, Rakesh K; Singh, Manoj Kumar

    2015-12-01

    Esthesioneuroblastoma (ENB) is a malignant neuroectodermal tumor. Hyams grading has an established role in its prognostication. The importance of microvessel density (MVD) and Ki-67 labeling index (Ki-67 LI) is well studied in various tumors, but the same remains understated in ENB. The aims of the study were to estimate proliferation index and MVD in ENB and to correlate them with Hyams grade. Twenty-six ENB cases diagnosed over a period of 5 years were included. Hyams grade, MVD, and Ki-67 LI were evaluated for each of them. The cases were categorized as low (Hyams grades 1 and 2) and high (Hyams grades 3 and 4) grades. Microvessel density and Ki-67 LI were correlated with grade. The treatment response was analyzed in different grades. The commonest histologic grade was 4 (42%). The mean Ki-67 LI was 2%, 8.2%, 30.8%, and 40.5% and mean MVD was 81.67/mm(2), 37/mm(2), 24/mm(2), and 25.2/mm(2) in grades 1, 2, 3, and 4, respectively. A statistically significant correlation of grade with Ki-67 LI (P < .001) and MVD (P < .007) was noted. Hyams grade in ENB correlates well with treatment response. Ki-67 LI is an important prognostic factor in ENB. We propose a cutoff of 25% for Ki-67 LI to differentiate low- vs high-grade ENB, but larger studies are needed for validation. Contrary to epithelial tumors, there is a decrease in MVD with increasing grade in ENB.

  13. Ki-67 Immunostaining and its Correlation with Microvessel Density in Patients with Mutiple Myeloma.

    PubMed

    Himani, Bhankar; Meera, Sikka; Abhimanyu, Sharma; Usha, Rusia

    2016-01-01

    To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, <0.001) and was significantly higher (<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%). MVD/mm2 was also significantly (<0.0001) higher in myeloma patients (range 62-237/mm2, mean 178.0/mm2) than controls (range 5.2-50/mm2, mean 18.3/mm2). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine, β2 microglobulin and skeletal lesions. Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy.

  14. Prognostic Significance of Microvessel Density Determining by Endoglin in Stage II Rectal Carcinoma: A Retrospective Analysis

    PubMed Central

    Martinovic, Zeljko; Kovac, Drazen; Martinovic, Mia

    2015-01-01

    Background. The role of endoglin in the Dukes B rectal cancer is still unexplored. The aim of this study was to examine the expression of endoglin (CD105) in resected rectal cancer and to evaluate the relationship between microvessels density (MVD), clinicopathological factors, and survival rates. Methods. The study included 95 primary rectal adenocarcinomas, corresponding to 67 adjacent and 73 distant normal mucosa specimens from surgical resection samples. Tumor specimens were paraffin-embedded and immunohistochemical staining for the CD105 endothelial antigen was performed to count CD105-MVD. For exact measurement of the CD105-MVD used a computer-integrated system Alphelys Spot Browser 2 was used. Results. The intratumoral CD105-MVD was significantly higher compared with corresponding adjacent mucosa (P < 0.0001) and distant mucosa specimens (P < 0.0001). There was no significant difference in the CD105-MVD according to patients age, gender, tumor location, grade of differentiation, histological type, depth of tumor invasion, and tumor size. The overall survival rate was significantly higher in the low CD105-MVD group of patients than in the high CD105-MVD group of patients (log-rank test, P = 0.0406). Conclusion. CD105-assessed MVD could help to identify patients with possibility of poor survival in the group of stage II RC. PMID:26089870

  15. VEGF, Flt-1, and microvessel density in primary tumors as predictive factors of colorectal cancer prognosis

    PubMed Central

    Zygoń, Justyna; Szajewski, Mariusz; Kruszewski, Wiesław Janusz; Rzepko, Robert

    2017-01-01

    Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival. PMID:28357103

  16. Clinicopathological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer

    PubMed Central

    KIMURA, YUTAKA; MOROHASHI, SATOKO; YOSHIZAWA, TADASHI; SUZUKI, TAKAHIRO; MOROHASHI, HAJIME; SAKAMOTO, YOSHIYUKI; KOYAMA, MOTOI; MURATA, AKIHIKO; KIJIMA, HIROSHI; HAKAMADA, KENICHI

    2016-01-01

    Colorectal cancer is a common malignant disease, the incidence of which is increasing worldwide, therefore, identifying novel prognostic factors to improve adjuvant therapeutic strategies or postoperative monitoring is required. Angiogenesis, which is assessed by microvessel density (MVD), is significant in tumor growth and metastasis. However, the association between angiogenesis and clinical outcome remains controversial. In the present study, 84 surgically resected cases of colorectal cancer were examined to clarify the clinicopathological significance of vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and cluster of differentiation (CD)34 expression levels. VEGF expression was identified to be significantly correlated with TP expression (r=0.45; P<0.0001) and MVD in the high VEGF expression group was observed to be significantly greater than that in the low VEGF expression group (P=0.0194). In the Dukes' stage D group, the MVD in the high TP expression group was significantly greater than that in the low TP expression group (P=0.0149). High VEGF expression was subsequently correlated with a short overall survival rate for patients exhibiting lymph node metastasis (P=0.0128); however, there was no significant difference in overall survival rate regarding the expression levels of TP and CD34. The results of the present study indicate that VEGF expression may serve as a prognostic factor for colorectal cancer patients exhibiting lymph node metastasis. Furthermore, angiogenesis, as assessed by MVD, is an important prognostic factor for tumor growth at the primary site. PMID:26676225

  17. Low Stromal Area and High Stromal Microvessel Density Predict Poor Prognosis in Pancreatic Cancer.

    PubMed

    Nishida, Takahiro; Yoshitomi, Hideyuki; Takano, Shigetsugu; Kagawa, Shingo; Shimizu, Hiroaki; Ohtsuka, Masayuki; Kato, Atsushi; Furukawa, Katsunori; Miyazaki, Masaru

    2016-04-01

    Excessive stroma is a unique property of cancer tissue of the pancreas. The aim of this study was to analyze the relationship of cancer stromal area (SA) and tumor microvessel density (MVD) with prognostic and clinicopathological findings. Pancreatic adenocarcinoma tissues obtained from 104 patients were subjected to cytokeratin 19 and CD31 double immunostaining to identify cancer cells and endothelial cells simultaneously. Stromal area and MVD were assessed in the same sections. Patients were divided into 2 groups for each analysis by the median value of the respective measure. Stromal area negatively correlated with MVD. The low SA group harbored more poorly differentiated carcinoma than the high SA group. Patients of the low SA group showed a higher incidence of hematogenous recurrence. As a consequence, patients in the low SA and the high MVD groups had poorer prognosis in terms of both disease-free survival and overall survival than their respective groups. Multivariate analysis showed that a low SA was an independent prognostic factor for disease-free and overall survival. Our data indicate that the stroma of pancreatic cancer may play an auxiliary role as a barrier to cancer cell invasion. The depletion of tumor stroma alone does not suppress pancreatic cancer progression.

  18. Evaluation of mast cell counts and microvessel density in reactive lesions of the oral cavity

    PubMed Central

    Kouhsoltani, Maryam; Moradzadeh Khiavi, Monir; Tahamtan, Shabnam

    2016-01-01

    Background. Reliable immunohistochemical assays to assess the definitive role of mast cells (MCs) and angiogenesis in the pathogenesis of oral reactive lesions are generally not available. The aim of the present study was to evaluate mast cell counts (MCC) and microvessel density (MVD) in oral reactive lesions and determine the correlation between MCC and MVD. Methods. Seventy-five cases of reactive lesions of the oral cavity, including pyogenic granuloma, fibroma, peripheral giant cell granuloma, inflammatory fibrous hyperplasia, peripheral ossifying fibroma (15 for each category) were immunohisto-chemically stained with MC tryptase and CD31. Fifteen cases of normal gingival tissue were considered as the control group. The mean MCC and MVD in superficial and deep connective tissues were assessed and total MCC and MVD was computed for each lesion. Results. Statistically significant differences were observed in MCC and MVD between the study groups (P < 0.001). MC tryptase and CD31 expression increased in the superficial connective tissue of each lesion in comparison to the deep con-nective tissue. A significant negative correlation was not found between MCC and MVD in oral reactive lesions (P < 0.001, r = -0.458). Conclusion. Although MCs were present in the reactive lesions of the oral cavity, a direct correlation between MCC and MVD was not found in these lesions. Therefore, a significant interaction between MCs and endothelial cells and an active role for MCs in the growth of oral reactive lesions was not found in this study. PMID:28096950

  19. Regional Contrast-Enhanced Ultrasonography (CEUS) Characteristics of Breast Cancer and Correlation with Microvessel Density (MVD).

    PubMed

    Leng, Xiaoling; Huang, Guofu; Ma, Fucheng; Yao, Lanhui

    2017-07-14

    BACKGROUND The aim of this study was to investigate the perfusion characteristics of different breast lesion regions in contrast-enhanced ultrasonography (CEUS). MATERIAL AND METHODS A total of 161 malignant and benign breast lesion cases were subjected to CEUS. Perfusion parameters were analyzed and compared between the central and peripheral lesion regions, and surrounding tissue. Mass section was marked with methylene blue. Samples were subjected to immunohistochemistry, and microvessel density (MVD) was calculated. RESULTS There were significant differences in perfusion performance between the central and peripheral lesion regions, and surrounding tissue. In the malignant tumors, the fast-in and fast-out pattern was the most common type in the peripheral region (57.98%), while the slow-in and slow-out patterns were the major types in the central region and surrounding tissue (49.58% and 57.98%, respectively). Compared with the surrounding tissue, the peripheral region in the cancers exhibited hyperechoic enhancement and fast-in and slow-out pattern, with large area under the curve (AUC), while the central region showed isoechoic enhancement and equally-in and slow-out pattern, with large AUC. In the benign lesions, the peripheral region exhibited hyperechoic enhancement and fast-in and fast-out pattern, with small AUC, while the central region showed isoechoic enhancement and equally-in and -out pattern, with the same AUC value. Moreover, the perfusion parameters in the central and peripheral regions were significantly associated with MVD. CONCLUSIONS It is more objective to evaluate the perfusion performance of breast lesions with the reference of surrounding tissue. Compared with the central region, the peripheral region could better reflect the perfusion characteristics of malignant lesions.

  20. Study of the Impact of Uterine Artery Embolization (UAE) on Endometrial Microvessel Density (MVD) and Angiogenesis

    SciTech Connect

    Tan Guosheng; Xiang Xianhong; Guo Wenbo; Zhang Bing; Chen Wei; Yang Jianyong

    2013-08-01

    PurposeTo investigate the influence of uterine artery embolization (UAE) on endometrial microvessel density (MVD) and angiogenesis.MethodsSixty female guinea pigs were divided into two groups, the control group (n = 15) and the UAE treatment group (n = 45). In the UAE group, tris-acryl gelatin microspheres were used to generate embolization. Animals were further divided into three subgroups, A1, A2, and A3 (n = 15 for each subgroup), with uterine specimens collected at 7-15, 16-30, and 31-45 days after UAE, respectively. Immunostaining for factor VIII and CD105 was performed to identify total endometrial MVD (MVD{sub FVIII}) and CD105-positive angiogenesis (MVD{sub CD105}) at the indicated time points after UAE.ResultsQuantitative analysis revealed that MVD{sub FVIII} significantly decreased in the A1 (11.40 {+-} 2.76, p < 0.05) and A2 (15.37 {+-} 3.06, p < 0.05) groups compared to the control group (19.40 {+-} 2.50), and was restored to normal in the A3 group (18.77 {+-} 2.69). UAE caused a temporal up-regulation of MVD{sub CD105}-positive angiogenesis in the A1 group (9.33 {+-} 2.37, p < 0.05) and the A2 group (11.63 {+-} 1.56, p < 0.05) compared to the control group (7.12 {+-} 1.67), and the MVD{sub CD105} value returned to normal in the A3 group (8.07 {+-} 1.97).ConclusionUAE caused a temporal decrease in endometrial MVD that reversed over time as a result of the increase of CD105-positive angiogenesis. Although the UAE-induced reduction of endometrial MVD was reversible, its long-term effect on endometrial receptivity still needs further study.

  1. Bone marrow microvessel density and plasma angiogenic factors in myeloproliferative neoplasms: clinicopathological and molecular correlations.

    PubMed

    Lekovic, Danijela; Gotic, Mirjana; Skoda, Radek; Beleslin-Cokic, Bojana; Milic, Natasa; Mitrovic-Ajtic, Olivera; Nienhold, Ronny; Sefer, Dijana; Suboticki, Tijana; Buac, Marijana; Markovic, Dragana; Diklic, Milos; Cokic, Vladan P

    2017-03-01

    Increased angiogenesis in BCR-ABL1 negative myeloproliferative neoplasms (MPNs) has been recognized, but its connection with clinical and molecular markers needs to be defined. The aims of study were to (1) assess bone marrow (BM) angiogenesis measured by microvessel density (MVD) using CD34 and CD105 antibodies; (2) analyze correlation of MVD with plasma angiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8; (3) examine the association of MVD with clinicopathological and molecular markers. We examined 90 de novo MPN patients (30 polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET)) and 10 age-matched controls. MVD was analyzed by immunohistochemistry "hot spot" method, angiogenic factors by immunoassay and JAK2V617F, and CALR mutations by DNA sequencing and allelic PCR. MVD was significantly increased in MPNs compared to controls (PMF > PV > ET). Correlation between MVD and plasma angiogenic factors was found in MPNs. MVD was significantly increased in patients with JAK2V617F mutation and correlated with JAK2 mutant allele burden (CD34-MVD: ρ = 0.491, p < 0.001; CD105-MVD: ρ = 0.276, p = 0.02) but not with CALR mutation. MVD correlated with leukocyte count, serum lactate dehydrogenase, hepatomegaly, and splenomegaly. BM fibrosis was significantly associated with CD34-MVD, CD105-MVD, interleukin-8, and JAK2 mutant allele burden. JAK2 homozygote status had positive predictive value (100%) for BM fibrosis. Patients with prefibrotic PMF had significantly higher MVD than patients with ET, and we could recommend MVD to be additional histopathological marker to distinguish these two entities. This study also highlights the strong correlation of MVD with plasma angiogenic factors, JAK2 mutant allele burden, and BM fibrosis in MPNs.

  2. ALK1 expression in oral lichen planus: a possible relation to microvessel density.

    PubMed

    Hazzaa, Hala H A; El-Wakeel, Naglaa M; Attia, Enas A S; Abo Hager, Eman A

    2016-05-01

    To assess the expression of activin receptor-like kinase 1 (ALK1) and investigate its possible relationship with microvessel density (MVD) in different forms of oral lichen planus (OLP) compared to controls' biopsies. Biopsies from 20 reticular/papular OLP (R/PLP), 20 atrophic/erosive OLP (A/ELP) patients, and 20 healthy subjects were immunohistochemically analyzed and statistically compared and correlated for ALK1 expression and MVD as assessed by CD34 expression. All OLP specimens revealed the presence of positive cytoplasmic CD34 immunostaining in endothelial cells, with statistically high significant MVD in each of R/PLP (Median; M = 4.40) and A/ELP (M = 7.69) compared to controls (M = 1.16) (P < 0.001). Statistically significant MVD was found in A/ELP compared to R/PLP (P < 0.001). All control specimens revealed negative ALK1 immunostaining of the few inflammatory cells found, while 85% of A/ELP cases and 70% of R/PLP cases showed positively immunostained sections for ALK-1, with statistically significant higher ALK1 expression In A/ELP (M = 1.95) compared to R/PLP (M = 0.86) (P = 0.005). No significant correlation between CD34 and ALK1 was detected in R/PLP (r = 0.081), while a barely moderate positive correlation was found in A/ELP (r = 0.396). ALK1 expression and MVD are increased in OLP, particularly in A/ELP type. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    PubMed

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p < .001) and VEGF expression (r = .35, p < .001). For the prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  4. Development and Validation of a Histological Method to Measure Microvessel Density in Whole-Slide Images of Cancer Tissue

    PubMed Central

    Croons, Valerie; Waumans, Yannick; Sluydts, Ellen; De Schepper, Stefanie; Andries, Luc; Waelput, Wim; Fransen, Erik; Vermeulen, Peter B.; Kockx, Mark M.; De Meyer, Guido R. Y.

    2016-01-01

    Despite all efforts made to develop predictive biomarkers for antiangiogenic therapies, no unambiguous markers have been identified so far. This is due to among others the lack of standardized tests. This study presents an improved microvessel density quantification method in tumor tissue based on stereological principles and using whole-slide images. Vessels in tissue sections of different cancer types were stained for CD31 by an automated and validated immunohistochemical staining method. The stained slides were digitized with a digital slide scanner. Systematic, uniform, random sampling of the regions of interest on the whole-slide images was performed semi-automatically with the previously published applications AutoTag and AutoSnap. Subsequently, an unbiased counting grid was combined with the images generated with these scripts. Up to six independent observers counted microvessels in up to four cancer types: colorectal carcinoma, glioblastoma multiforme, ovarian carcinoma and renal cell carcinoma. At first, inter-observer variability was found to be unacceptable. However, after a series of consensus training sessions and interim statistical analysis, counting rules were modified and inter-observer concordance improved considerably. Every CD31-positive object was counted, with exclusion of suspected CD31-positive monocytes, macrophages and tumor cells. Furthermore, if interconnected, stained objects were considered a single vessel. Ten regions of interest were sufficient for accurate microvessel density measurements. Intra-observer and inter-observer variability were low (intraclass correlation coefficient > 0.7) if the observers were adequately trained. PMID:27583442

  5. Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: Results of RTOG 9505

    SciTech Connect

    Foote, Robert L. . E-mail: foote.robert@mayo.edu; Weidner, Noel; Harris, Jonathan; Hammond, Elizabeth; Lewis, Jean E.; Vuong, Te; Ang, K. Kian; Fu, Karen K.

    2005-03-01

    Purpose: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. Methods and materials: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD < 60 vs. {>=}60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. Results: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. Conclusions: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD < 60 vs. MVD {>=}60. The study was perhaps limited by the small size of the NPC samples.

  6. Correlation between CT Perfusion Parameters and Microvessel Density and Vascular Endothelial Growth Factor in Adrenal Tumors

    PubMed Central

    Wang, Xifu; Bai, Renju; Li, Yajun; Zhao, Jinkun

    2013-01-01

    We evaluated the correlation between computed tomography (CT) perfusion parameters and markers of angiogenesis in adrenal adenomas and non-adenomas to determine if perfusion CT can be used to distinguish between them. Thirty-four patients with pathologically-confirmed adrenal tumors (17 adenomas, 17 non-adenomas) received CT perfusion imaging before surgery. CT perfusion parameters (blood flow [BF], blood volume [BV], mean transit time [MTT], and permeability surface area product [PS]) were calculated. Tumor tissue sections were examined with immunohistochemical methods for vascular endothelial growth factor (VEGF) expression and microvessel density (MVD). The mean age of the 34 patients was 43 years. The median BV was significantly higher in adenomas than in non-adenomas [12.3 ml/100 g, inter-quartile range (IQR): 10.4 to 16.5 ml/100 g vs. 8.8 ml/100 g, IQR: 3.3 to 9.4 ml/100 g, p = 0.001]. Differences in BF, MTT, and PS parameter values between adenomas and non-adenomas were not significant (p>0.05). The mean MVD was significantly higher in adenomas compared to non-adenomas (98.5±28.5 vs. 53.5±27.0, p<0.0001). Adenomas also expressed significantly higher median VEGF than non-adenomas (65%, IQR: 50 to 79% vs. 45%, IQR: 35 to 67%, p = 0.02). A moderately strong correlation between BF and VEGF (r = 0.53, p = 0.03) and between BV and MVD among adenomas (r = 0.57, p = 0.02) exist. Morphology, MVD, and VEGF expression in adenomas differ significantly from non-adenomas. Of the CT perfusion parameters examined, both BF and BV correlate with MVD, but only BF correlates with VEGF, and only in adenomas. The significant difference in BV suggests that BV may be used to differentiate adenomas from non-adenomas. However, the small difference in BV shows that it may only be possible to use BV to identify adenomas vs. non-adenomas at extreme BV values. PMID:24260316

  7. Study of the impact of uterine artery embolization (UAE) on endometrial microvessel density (MVD) and angiogenesis.

    PubMed

    Tan, Guosheng; Xiang, Xianhong; Guo, Wenbo; Zhang, Bing; Chen, Wei; Yang, Jianyong

    2013-08-01

    To investigate the influence of uterine artery embolization (UAE) on endometrial microvessel density (MVD) and angiogenesis. Sixty female guinea pigs were divided into two groups, the control group (n = 15) and the UAE treatment group (n = 45). In the UAE group, tris-acryl gelatin microspheres were used to generate embolization. Animals were further divided into three subgroups, A1, A2, and A3 (n = 15 for each subgroup), with uterine specimens collected at 7-15, 16-30, and 31-45 days after UAE, respectively. Immunostaining for factor VIII and CD105 was performed to identify total endometrial MVD (MVDFVIII) and CD105-positive angiogenesis (MVDCD105) at the indicated time points after UAE. Quantitative analysis revealed that MVDFVIII significantly decreased in the A1 (11.40 ± 2.76, p < 0.05) and A2 (15.37 ± 3.06, p < 0.05) groups compared to the control group (19.40 ± 2.50), and was restored to normal in the A3 group (18.77 ± 2.69). UAE caused a temporal up-regulation of MVDCD105-positive angiogenesis in the A1 group (9.33 ± 2.37, p < 0.05) and the A2 group (11.63 ± 1.56, p < 0.05) compared to the control group (7.12 ± 1.67), and the MVDCD105 value returned to normal in the A3 group (8.07 ± 1.97). UAE caused a temporal decrease in endometrial MVD that reversed over time as a result of the increase of CD105-positive angiogenesis. Although the UAE-induced reduction of endometrial MVD was reversible, its long-term effect on endometrial receptivity still needs further study.

  8. The effects of binge alcohol exposure in the 2nd trimester on the estimated density of cerebral microvessels in near-term fetal sheep.

    PubMed

    Simon, Katherine E; Mondares, Robin L; Born, Donald E; Gleason, Christine A

    2008-09-22

    Heavy fetal alcohol exposure is associated with a spectrum of neurological abnormalities, although the mechanism of injury is largely unknown. We previously reported attenuated cerebral blood flow response to hypoxia in fetal and newborn sheep which were exposed to alcohol earlier in pregnancy. One possible mechanism for this effect of alcohol on the developing cerebral vasculature is a decrease in cerebral microvessel density, similar to its effect on developing neurons. Therefore, we tested the hypothesis that prenatal alcohol exposure decreases cerebral microvessel density. Pregnant ewes received intravenous infusions of ethanol or saline during days 60-84 of gestation (term=150 days) and at 125 days of gestation we obtained the fetal brains for study. We immunohistochemically labeled vessels of the left cerebral forebrain hemispheres with antibody to endothelial nitric oxide synthase and then obtained unbiased stereological estimates of cerebral microvessel density using a modified optical fractionator method. We studied 20 fetal brains of which 9 were alcohol-exposed, 11 were saline-controls, and all were products of a twin gestation. Although brain and body weights were not different between groups, the alcohol-exposed group had significantly lower brain weight as a percentage of body weight. Estimates of cerebral microvessel density were not significantly different between alcohol-exposed and saline-control groups: 12.7+/-8.7 and 9.1+/-2.8 microvessels per mm(3), respectively (mean+/-SD, p=0.32). Since there is no change in estimated cerebral microvessel density after prenatal alcohol exposure, we conclude that decreased cerebral microvessel density is not a likely explanation for attenuated cerebral blood flow in response to hypoxia.

  9. Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases.

    PubMed

    Martinez, Leandro Marcelo; Labovsky, Vivian; Calcagno, María de Luján; Davies, Kevin Mauro; Rivello, Hernán Garcia; Wernicke, Alejandra; Calvo, Juan Carlos; Chasseing, Norma Alejandra

    2016-04-01

    Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. High eIF4E, VEGF, and Microvessel Density in Stage I to III Breast Cancer

    PubMed Central

    Byrnes, Kerry; White, Stephen; Chu, Quyen; Meschonat, Carol; Yu, Herbert; Johnson, Lester W.; DeBenedetti, Arrigo; Abreo, Fleurette; Turnage, Richard H.; McDonald, John C.; Li, Benjamin D.

    2006-01-01

    Objective: In a prospective trial, to determine if eIF4E overexpression in breast cancer specimens is correlated with VEGF elevation, increased tumor microvessel density (MVD) counts, and a worse clinical outcome irrespective of nodal status. Summary and Background Data: In vitro, the overexpression of eukaryotic initiation factor 4E (eIF4E) up-regulates the translation of mRNAs with long 5′-untranslated regions (5′-UTRs). One such gene product is the vascular endothelial growth factor (VEGF). Methods: A total of 114 stage I to III breast cancer patients were prospectively accrued and followed with a standardized clinical surveillance protocol. Cancer specimens were quantified for eIF4E, VEGF, and MVD. Outcome endpoints were cancer recurrence and cancer-related death. Results: eIF4E overexpression was found in all cancer specimens (mean ± SD, 12.5 ± 7.6-fold). Increasing eIF4E overexpression correlated with increasing VEGF elevation (r = 0.24, P = 0.01, Spearman's coefficient), and increasing MVD counts (r = 0.35, P < 0.0002). Patients whose tumor had high eIF4E overexpression had shorter disease-free survival (P = 0.004, log-rank test) and higher cancer-related deaths (P = 0.002) than patients whose tumors had low eIF4E overexpression. Patients with high eIF4E had a hazard ratio for cancer recurrence and cancer-related death of 1.8 and 2.1 times that of patients with low eIF4E (respectively, P = 0.009 and P = 0.002, Cox proportional hazard model). Conclusions: In breast cancer patients, increasing eIF4E overexpression in the cancer specimens correlates with higher VEGF levels and MVD counts. Patients whose tumors had high eIF4E overexpression had a worse clinical outcome, independent of nodal status. Thus, eIF4E overexpression in breast cancer appears to predict increased tumor vascularity and perhaps cancer dissemination by hematogenous means. PMID:16633004

  11. Detection and quantification of mast cell, vascular endothelial growth factor, and microvessel density in human inflammatory periapical cysts and granulomas.

    PubMed

    Fonseca-Silva, T; Santos, C C O; Alves, L R; Dias, L C; Brito, M; De Paula, A M B; Guimarães, A L S

    2012-09-01

    To identify and quantify mast cell (MC), vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in human periapical cysts and granulomas. Archived samples of cysts (n = 40) and granulomas (n = 28) were sectioned and stained with toluidine blue. MCs were identified and counted. Immunohistochemical reactions were employed to evaluate the tissue expression of VEGF and vessels. MVD was estimated by determining the areas of tissue labelled with CD31 antibody. The data were analysed using the Mann-Whitney test (P < 0.05). MCs were observed in the peripheral regions of both lesion types, whilst VEGF and MVD were distributed in the stroma. The presence of MCs was higher in cysts than in granulomas (P < 0.05). VEGF and MVD expression were similar in these lesions. The highest number of MCs was observed in cysts. Moreover, the identification of VEGF and MVD was consistent with the immune mechanisms involved in the lesions. © 2012 International Endodontic Journal.

  12. Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease.

    PubMed

    Erbil, Yeşim; Ozluk, Yasemin; Giriş, Murat; Salmaslioglu, Artur; Issever, Halim; Barbaros, Umut; Kapran, Yersu; Ozarmağan, Selçuk; Tezelman, Serdar

    2007-06-01

    Although some endocrine surgeons administer Lugol solution to decrease thyroid gland vascularity, there is still not an agreement on its effectiveness. The aims of this clinical trial are to evaluate thyroid blood flow and microvessel density in patients with Graves' disease who received Lugol solution treatment preoperatively. This was a prospective clinical trial. This clinical trial took place at a tertiary referral center. Thirty-six patients were randomly assigned to receive either preoperative treatment with Lugol solution (group 1, n = 17) or no preoperative treatment with Lugol solution (group 2, n = 19). Blood flow through the thyroid arteries of patients with Graves' disease was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed by immunohistochemical and Western blot analysis of the level of expression of CD-34 in thyroid tissue. The weight and blood loss of the thyroid gland were measured in all patients. The mean blood flow, MVD, CD-34 expression, and blood loss in group 1 patients were significantly lower than those in group 2 patients. There was a negative correlation between Lugol solution treatment and blood flow (r(s) = -0.629; P = 0.0001), blood loss (r(s) = -0.621; P = 0.0001), MVD (r(s) = -0.865; P = 0.0001), and CD-34 expression (r(s) = -0.865; P = 0.0001). According to logistic regression analysis, Lugol solution treatment resulted in a 9.33-fold decreased rate of intraoperative blood loss. Preoperative Lugol solution treatment decreased the rate of blood flow, thyroid vascularity, and intraoperative blood loss during thyroidectomy.

  13. Clinical study of contrast-enhanced digital mammography and the evaluation of blood and lymphatic microvessel density

    PubMed Central

    Cruz-Bastida, Juan P; Rosado-Méndez, Iván M; Villaseñor-Navarro, Yolanda; Pérez-Ponce, Héctor; Galván, Héctor A; Trujillo-Zamudio, Flavio E; Sánchez-Suárez, Patricia; Benítez-Bribiesca, Luis

    2016-01-01

    Objective: To correlate image parameters in contrast-enhanced digital mammography (CEDM) with blood and lymphatic microvessel density (MVD). Methods: 18 Breast Imaging-Reporting and Data System (BI-RADS)-4 to BI-RADS-5 patients were subjected to CEDM. Craniocaudal views were acquired, two views (low and high energy) before iodine contrast medium (CM) injection and four views (high energy) 1–5 min afterwards. Processing included registration and two subtraction modalities, traditional single-energy temporal (high-energy) and “dual-energy temporal with a matrix”, proposed to improve lesion conspicuity. Images were calibrated into iodine thickness, and iodine uptake, contrast, time–intensity and time–contrast kinetic curves were quantified. Image indicators were compared with MVD evaluated by anti-CD105 and anti-podoplanin (D2-40) immunohistochemistry. Results: 11 lesions were cancerous and 7 were benign. CEDM subtraction strongly increased conspicuity of lesions enhanced by iodine uptake. A strong correlation was observed between lymphatic vessels and blood vessels; all benign lesions had <30 blood microvessels per field, and all cancers had more than this value. MVD showed no correlation with iodine uptake, nor with contrast. The most frequent curve was early uptake followed by plateau for uptake and contrast in benign and malignant lesions. The positive-predictive value of uptake dynamics was 73% and that of contrast was 64%. Conclusion: CEDM increased lesion visibility and showed additional features compared with conventional mammography. Lack of correlation between image parameters and MVD is probably due to tumour tissue heterogeneity, mammography projective nature and/or dependence of extracellular iodine irrigation on tissue composition. Advances in knowledge: Quantitative analysis of CEDM images was performed. Image parameters and MVD showed no correlation. Probably, this is indication of the complex dependence of CM perfusion on tumour

  14. Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

    PubMed Central

    2010-01-01

    Background Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400× magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of

  15. Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral Amyloidosis.

    PubMed

    Ielacqua, Giovanna D; Schlegel, Felix; Füchtemeier, Martina; Xandry, Jael; Rudin, Markus; Klohs, Jan

    2015-01-01

    Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcAβ mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the brain with dynamic gradient echo planar imaging (EPI). From this measurements relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF) were estimated. For the same animal maps of the relaxation shift index Q were computed from high resolution gradient echo and spin echo data that were acquired before and after superparamagnetic iron oxide (SPIO) nanoparticle injection. Q-values were used to derive estimates of microvessel density. The change in the relaxation rates [Formula: see text] obtained from pre- and post-contrast gradient echo data was used for the alternative determination of rCBV [rCBV([Formula: see text])]. Linear mixed effects modeling found no significant association between rCBV(DSC), rCBV([Formula: see text]), rCBF, and Q with genotype in 13-month old mice [compared to age-matched non-transgenic littermates (NTLs)] for any of the evaluated brain regions. In 24-month old mice there was a significant association for rCBV(DSC) with genotype in the cerebral cortex, and for rCBV([Formula: see text]) in the cerebral cortex and cerebellum. For rCBF there was a significant association in the cerebellum but not in other brain regions. Q-values in the olfactory bulb, cerebral cortex, striatum, hippocampus, and cerebellum in 24-month old mice were significantly associated with genotype. In those regions Q-values were reduced between 11 and 26% in arcAβ mice compared to age-matched NTLs. Vessel staining with CD31 immunohistochemistry confirmed a

  16. Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAβ Mouse Model of Cerebral Amyloidosis

    PubMed Central

    Ielacqua, Giovanna D.; Schlegel, Felix; Füchtemeier, Martina; Xandry, Jael; Rudin, Markus; Klohs, Jan

    2016-01-01

    Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcAβ mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the brain with dynamic gradient echo planar imaging (EPI). From this measurements relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF) were estimated. For the same animal maps of the relaxation shift index Q were computed from high resolution gradient echo and spin echo data that were acquired before and after superparamagnetic iron oxide (SPIO) nanoparticle injection. Q-values were used to derive estimates of microvessel density. The change in the relaxation rates ΔR2* obtained from pre- and post-contrast gradient echo data was used for the alternative determination of rCBV [rCBV(ΔR2*)]. Linear mixed effects modeling found no significant association between rCBV(DSC), rCBV(ΔR2*), rCBF, and Q with genotype in 13-month old mice [compared to age-matched non-transgenic littermates (NTLs)] for any of the evaluated brain regions. In 24-month old mice there was a significant association for rCBV(DSC) with genotype in the cerebral cortex, and for rCBV(ΔR2*) in the cerebral cortex and cerebellum. For rCBF there was a significant association in the cerebellum but not in other brain regions. Q-values in the olfactory bulb, cerebral cortex, striatum, hippocampus, and cerebellum in 24-month old mice were significantly associated with genotype. In those regions Q-values were reduced between 11 and 26% in arcAβ mice compared to age-matched NTLs. Vessel staining with CD31 immunohistochemistry confirmed a reduction of microvessel density in the old arcAβ mice

  17. COX-2 expression correlates with microvessel density in non-melanoma skin cancer from renal transplant recipients and immunocompetent individuals.

    PubMed

    O'Grady, Anthony; O'Kelly, Patrick; Murphy, Gillian M; Leader, Mary; Kay, Elaine

    2004-12-01

    Angiogenesis, the generation of a new vascular network, is regulated in part by inducers of endothelial cell migration and proliferation, such as cyclooxygenase-2 (COX-2). Microvessel density (MVD) measurement is widely used to quantify angiogenesis in tissue sections of tumors, including cutaneous malignancies. The increasing number of successful renal transplantations worldwide is producing a progressive increase in patients at risk for non-melanoma skin cancers, such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and Bowen's disease (BD), and at significantly increased risk for metastatic SCC. The aim of this study was to investigate whether there was any difference in angiogenesis between these tumor types in renal transplant recipients (RTRs) and immunocompetent individuals (ICIs) and whether angiogenesis in these tumors was related to COX-2 expression. The study measured angiogenesis and COX-2 expression in BD, SCC, BCC, and normal skin from both RTRs and ICIs. Vessel counts were performed, and COX-2 immunoexpression was assessed semiquantitatively. The MVD counts differed significantly between normal skin and all tumor types. Significant differences in MVD density were found between all SCCs and BCCs. BCCs from RTRs had significantly greater MVD at the invasive front of the tumor than BCCs from ICIs. Increased COX-2 expression correlated with increased MVD in all tumors examined. These findings indicate a difference in vascular profiles between RTRs and ICIs in BCCs and suggest a relationship between COX-2 and angiogenesis that may provide a possible treatment target for skin tumors in these 2 patient populations.

  18. Immunohistochemical expression of vascular endothelial growth factor (VEGF) does not correlate with microvessel density in renal cell carcinoma.

    PubMed

    Raica, M; Cimpean, A M; Anghel, A

    2007-01-01

    The aim of present study was to investigate the relationship between the immunohistochemical expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) assessed by CD31 and endoglin (CD105) in renal cell carcinoma (RCC). Specimens from 45 cases of RCC. were formalin-fixed, paraffin embedded, and sections were stained with H&E. Additional sections from each case were stained for VEGF, CD31, CD105, and alpha smooth muscle cell actin (SMA). VEGF immunohistochemical expression was estimated as negative (0), weak positive (+1), moderate positive (+2), and intense positive (+3). Microvessel density (MVD) was estimated on 5 hot spots (x400) from each case, and the arithmetic media was the final result. MVD was separately calculated on slides stained with CD31 and CD105. The rate between mature and immature blood vessels was calculated on slides stained with CD31/CD105/SMA. Statistic analysis was performed with SPSS10.0. The immunoreaction for VEGF was positive in epithelial cells of the renal tubules, and occasionally, in endothelial cells. In RCC, tumor cells were positive in 34 from 45 cases (75.5%). 11 cases were negative, 14 were slightly positive (+1), 13 moderate (+2), and 7 intense (+3). No relationship was found between the expression of VEGF and pathological form and nuclear grade, excepting for the chromophilic variant (3 cases, all positive). CD31 was positive in all cases, and CD105 in 39 cases. The mean values of MVD on slides stained for CD31 and CD105 were: 31.68 (range 9.8-60.2)/20.66 (range 4.2-52.8). The rate CD31/SMA positive blood vessels was 1/0.62. VEGF was expressed in 75.5% of 45 cases with RCC, and the mean value of MVD CD31/CD105 was 31.68/20.66. The immunohistochemical expression of VEGF does not correlate with MVD performed on slides stained for both CD31 and endoglin. The majority of blood vessels in the tumor area are of mature type, with perivascular cells positive for SMA.

  19. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images

    PubMed Central

    Kather, Jakob Nikolas; Marx, Alexander; Reyes-Aldasoro, Constantino Carlos; Schad, Lothar R.; Zöllner, Frank Gerrit; Weis, Cleo-Aron

    2015-01-01

    Blood vessels in solid tumors are not randomly distributed, but are clustered in angiogenic hotspots. Tumor microvessel density (MVD) within these hotspots correlates with patient survival and is widely used both in diagnostic routine and in clinical trials. Still, these hotspots are usually subjectively defined. There is no unbiased, continuous and explicit representation of tumor vessel distribution in histological whole slide images. This shortcoming distorts angiogenesis measurements and may account for ambiguous results in the literature. In the present study, we describe and evaluate a new method that eliminates this bias and makes angiogenesis quantification more objective and more efficient. Our approach involves automatic slide scanning, automatic image analysis and spatial statistical analysis. By comparing a continuous MVD function of the actual sample to random point patterns, we introduce an objective criterion for hotspot detection: An angiogenic hotspot is defined as a clustering of blood vessels that is very unlikely to occur randomly. We evaluate the proposed method in N=11 images of human colorectal carcinoma samples and compare the results to a blinded human observer. For the first time, we demonstrate the existence of statistically significant hotspots in tumor images and provide a tool to accurately detect these hotspots. PMID:26061817

  20. Correlation of intratumoral lymphatic microvessel density, vascular endothelial growth factor C and cell proliferation in salivary gland tumors.

    PubMed

    Americo, Márcia Gimenes; Marques, Yonara Maria Freire Soares; El Abras Ankha, Milagros Del Valle; do Prado, Renata Falchete; Carvalho, Yasmin Rodarte

    2017-03-01

    Lymphatic dissemination is one of the most important pathways for metastasis in many solid tumors, including head and neck carcinomas. The lymphatic growth of cancer has been used as a significant independent adverse prognostic factor and provides information about tumor progression. Salivary gland tumors present different prognoses and have the ability to develop metastases; however, this information regarding the lymphatic spread is scarce. This paper quantifies the lymphatic microvessel density (LMD) in benign and malignant salivary gland tumors and analyzes the relationship between LMD and tumor expression of vascular endothelial growth factors C (VEGF-C) and the proliferative index. The results show that there is no correlation between LMD, VEGF-C and the proliferative index in the majority of salivary gland tumors analyzed, apart from polymorphous low-grade carcinoma which exhibits statistical correlation between LMD and the proliferative index (p < 0.05). This correlation probably does not indicate a poor prognosis for this PLGA, since this is a low metastasizing carcinoma of the salivary glands. Different from other solid tumors, such as breast or prostatic carcinomas, there is no correlation between VEGF-C and LMD in salivary gland tumors, and so these traits are not able to estimate the metastatic risk or the prognosis of these tumors.

  1. Identification of lymphatic vessels and prognostic value of lymphatic microvessel density in lesions of the uterine cervix.

    PubMed

    Saptefraţi, L; Cîmpean, Anca Maria; Ciornîi, A; Ceauşu, Raluca; Eşanu, N; Raica, M

    2009-01-01

    Incomplete characterization of the uterine cervix cancer from molecular point of view represents the main problem for the use of a proper therapy in this disease. Few data are available about D2-40 expression in lymphatic endothelial cells and also in tumor cells from uterine cervix cancer. The aim of the present work was to study the involvement of lymphatics in prognosis and tumor progression of the uterine cervix lesions. We used D2-40 immunostaining to highlight lymphatic vessels from squamous cell metaplasia (n=17), cervical intraepithelial neoplasia (n=11), carcinoma in situ (n=3), microinvasive carcinoma (n=4) and invasive carcinoma (n=19) using Avidin-Biotin technique (LSAB+). Type and distribution of lymphatics in different lesions of the cervix were analyzed. We found significant correlation between lymphatic microvessel density and tumor grade and particular distribution of the lymphatics linked to histopathologic type of the lesions. Also, differences was found in lymphovascular invasion interpretation between routine Hematoxylin and Eosin staining specimens and immunohistochemical ones. Our results showed differences in the distribution and D2-40 expression in lymphatic vessels and tumor cells from the cervix lesions linked to histopathology and tumor grade.

  2. Atypical variants of nodular lymphocyte-predominant Hodgkin lymphoma show low microvessel density and vessels of distention type.

    PubMed

    Scheidt, Victoria; Hansmann, Martin-Leo; Schuhmacher, Bianca; Döring, Claudia; Hartmann, Sylvia

    2017-02-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) presents different histopathologic growth patterns, including atypical forms showing overlapping histopathologic and clinical features with T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). Because growth patterns are associated with vessel distribution, the aim of the present study was to compare angiogenesis in different NLPHL patterns with THRLBCL as well as other lymphomas. Atypical variants of NLPHL and THRLBCL (n=10 per group) both showed a low microvessel density (MVD; 1.16-1.31/μm(2)) with a diffuse vessel distribution. In contrast, in typical NLPHL (n=10), follicular areas with low MVD were retained, whereas an increase in vessels in the interfollicular areas was observed (MVD 1.35/μm(2)). THRLBCL and typical NLPHL could additionally be distinguished by differences in their molecular angiogenesis signature. Furthermore, the number of intravascular T cells was significantly reduced in THRLBCL (0.0028 T cells/mm(2) vessel area) when compared with typical NLPHL (0.0059 T cells/mm(2) vessel area), potentially reflecting the different composition of the microenvironment in these 2 lymphoma entities. The results of our study reveal a similar vascular pattern and angiogenesis behavior in atypical NLPHL variants and THRLBCL in contrast to the retained follicular pattern in typical NLPHL. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

    PubMed

    Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

    2016-04-01

    The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p < 0.0001). Microvessel density was decreased in liver metastases from patients treated with bevacizumab in comparison to those from untreated/chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect.

  4. Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases.

    PubMed

    Tse, Gary M K; Lui, Philip C W; Lee, C Soon; Kung, Fred Y l; Scolyer, Richard A; Law, Bonita K B; Lau, Tai-Shing; Karim, Rooshdiya; Putti, Thomas C

    2004-09-01

    A retrospective review of 185 mammary phyllodes tumors (105 benign, 51 borderline, 29 malignant) from 4 centers was performed by immunohistochemistry to investigate the expression of vascular endothelial growth factor in the epithelial and stromal cells of mammary phyllodes tumors. The correlation of vascular endothelial growth factor with tumor grade, stromal cell nuclear pleomorphism, cellularity, mitotic rate, margin histomorphology, and the stromal microvessel density was evaluated. Vascular endothelial growth factor expression was found in the epithelium in 29% and in the stromal cells in 31% of cases. There was significant increase of vascular endothelial growth factor expression in the stromal cells with increasing degree of malignancy, but not the epithelium. Microvessel density in the stroma also showed significant correlation with tumor malignancy, and a correlation was shown with the stromal vascular endothelial growth factor expression. Statistical overlap of stromal vascular endothelial growth factor and microvessel density in predicting malignancy suggests that angiogenesis may be an effector mechanism for vascular endothelial growth factor. Assessment of stromal VEGF may be useful as an adjunctive diagnostic criterion in the histologic assessment of malignancy in phyllodes tumors.

  5. Finasteride reduces microvessel density and expression of vascular endothelial growth factor in renal tissue of diabetic rats.

    PubMed

    Tian, He-lin; Zhao, Chao-xian; Wu, Hai-ying; Xu, Zhong-xin; Wei, Li-shun; Zhao, Ru-tong; Jin, Dong-ling

    2015-06-01

    Vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of diabetic microvascular complications. Finasteride has been confirmed to decrease VEGF expression in prostate and prostatic suburethral tissue resulting in limiting hematuria from human benign prostatic hyperplasia. The purpose of this study was to evaluate the effects of finasteride on microvessel density (MVD), VEGF protein and mRNA expressions in the renal tissue of diabetic rats. Diabetic rats induced by streptozotocin were intragastrically given finasteride at 30 mg/kg body weight once a day for 4 weeks. Histomorphologic changes in kidney were observed under light microscope. Immunohistochemistry for CD34 and VEGF on kidney sections was performed to assess MVD and VEGF protein expression in glomeruli of rats, respectively. The VEGF mRNA expression in the renal tissue was examined using reverse transcription polymerase chain reaction analysis. The glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue were significantly increased in diabetic rats and finasteride-treated rats when compared with controls (P < 0.01, P < 0.05). When compared with diabetic rats, the glomerular tuft area, glomerular volume, MVD, VEGF protein expression in glomeruli and VEGF mRNA expression in the renal cortex tissue of finasteride-treated rats were significantly decreased (P < 0.05, P < 0.01). Finasteride reduces the VEGF expression and decreases the MVD in the renal tissue of diabetic rats, suggesting the therapeutic potential of finasteride on diabetic microvascular complications.

  6. Contrast-Enhanced Ultrasound Differentiation Between Low and High-Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density.

    PubMed

    Guo, Suping; Xu, Pan; Zhou, Aiyun; Wang, Gongxian; Chen, Weimin; Mei, Jinhong; Xiao, Fan; Liu, Juan; Zhang, Cheng

    2017-05-27

    Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD). The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34. Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01). Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis. © 2017 by the American Institute of Ultrasound in Medicine.

  7. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia.

    PubMed

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki

  8. Hypoxia-Related Marker GLUT-1, CAIX, Proliferative Index and Microvessel Density in Canine Oral Malignant Neoplasia

    PubMed Central

    Meier, Valeria; Guscetti, Franco; Roos, Malgorzata; Ohlerth, Stefanie; Pruschy, Martin; Rohrer Bley, Carla

    2016-01-01

    For various types of tumor therapy, it is suggested that co-targeting of tumor microenvironment, mainly tumor vasculature, mediates tumor response mechanisms. Immunohistochemistry for glucose transporter-1 (GLUT-1), carbonic anhydrase-IX (CAIX), Ki-67, and von Willebrand factor VIII for microvessel density (MVD) were performed on formalin-fixed paraffin-embedded samples of canine oral malignant neoplasms. Polarographic oxygen measurements (median pO2) and perfusion data via contrast-enhanced power Doppler ultrasound (median vascularity, median blood volume) provided additional information. Ninety-two samples were analyzed: sarcomas (n = 32), carcinomas (n = 30), and malignant melanomas (n = 30). Polarographic oxygen and perfusion data was available in 22.8% (sarcomas n = 9, carcinomas n = 7, melanomas n = 5), and 27.1% (sarcomas n = 10, carcinomas n = 8, melanomas n = 7) of cases, respectively. GLUT-1 expression was detected in 46.7% of all samples, and was generally weak. CAIX expression was found in 34.8% of all samples. Median Ki-67 score and MVD count was 19% and 17, respectively. The evaluation of the GLUT-1 score and continuous data showed significantly lower GLUT-1 levels in sarcomas (mean 5.1%, SD 6.2) versus carcinomas and melanomas (mean 16.5%/ 19.0%, SD 17.3/ 20.9, p = 0.001). The expression of CAIX correlated mildly positively with GLUT-1 (p = 0.018, rho = 0.250) as well as with Ki-67 (p = 0.014, rho = 0.295). MVD showed a significantly lower level in melanomas (mean 12.6, SD 7.7) versus sarcomas and carcinomas (mean 21.8/ 26.9, SD 13.0/20.4, p = 0.001). Median vascularity and blood volume were significantly lower in sarcomas (mean 10.4%, SD 11.0, and mean 6.3%, SD 6.5, respectively) versus carcinomas (mean 39.2%, SD 16.4 and mean 33.0%, SD 25.6, respectively) and melanomas (mean 36.0%, SD 18.3, and 31.5%, SD 24.5). Between the 3 histological groups, there was neither a significant difference in the GLUT-1 and CAIX score and continuous data, nor the Ki

  9. Prognostic value of microvessel density and p53 expression on the locoregional metastasis and survival of the patients with head and neck squamous cell carcinoma.

    PubMed

    de Oliveira, Marcos Vinícius M; Pereira Gomes, Erika P; Pereira, Camila S; de Souza, Ludmilla R; Barros, Lucas O; Mendes, Danilo C; Guimarães, André L S; De Paula, Alfredo M B

    2013-10-01

    Cancer cells need to develop microvessels in order to grow and to establish metastatic foci. A role for the p53 protein in the regulation of the angiogenic process is suggested. This study aimed to investigate the relationship between immunohistochemical expression of microvessel density (MVD), measured by CD31 staining, and p53 protein with clinicopathologic factors, and survival in head and neck squamous cell carcinoma (n=70). Tumor angiogenesis was estimated by determining MVD in areas with the highest number of stained microvessels (hot spots). Clinicopathologic factors and immunohistochemical data were evaluated by χ statistical test and were submitted to binary logistic regression to analyze the risk of presence of lymph node metastasis. Factors that might predict survival were investigated using Cox proportional hazards tests. Differences were considered statistically significant when P<0.05. The percentage of p53-positive cells showed no association with clinicopathologic parameters and MVD. Patients with locoregional metastasis presented statistically significant higher MVD (P=0.043). Individuals presenting head and neck squamous cell carcinoma in posterior sites (P=0.022; OR=3.644) and higher MVD (P=0.039; OR=3.247) had a significant increase in risk of metastasis occurrence. Multivariate analysis showed that presence of lymph node metastasis was statistically significant for overall survival of head and neck carcinoma patients (P=0.006; OR =2.917). The present data suggest that MVD represents a promising diagnostic tool to identify individuals with increased risk for the development of metastatic disease, which is very indicative of poor prognosis.

  10. Id-1 overexpression in invasive ductal carcinoma cells is significantly associated with intratumoral microvessel density in ER-negative/node-positive breast cancer.

    PubMed

    Jang, Ki-Seok; Han, Hong Xiu; Paik, Seung Sam; Brown, Powel H; Kong, Gu

    2006-12-08

    The aim of this study is to investigate the possible role of inhibitor of DNA binding (Id-1) overexpression in human breast cancer. We examined Id-1 expression by immunohistochemistry in 263 human breast cancers, 15 in situ lesions and 248 invasive cancers to investigate the relationship between its expression and various clinicopathological factors. Id-1 expression was significantly higher in invasive ductal carcinoma than in in situ ductal carcinoma or other invasive cancer subtypes (P=0.029 and 0.006, respectively). We also examined the association between Id-1 expression and tumor angiogenesis by measuring microvessel densities (MVD). Regarding the endothelial cells of microvessels showed negative or very weak Id-1 expression, Id-1 overexpression was found to be significantly related to MVD (P=0.014). Furthermore, Id-1 overexpression was found to be significantly associated with higher MVD in the ER-negative and node-involved subgroups of breast cancer (P=0.040 and 0.046, respectively). These data indicate that Id-1 overexpression is significantly associated with tumor angiogenesis, especially in the ER-negative and node-positive subtypes of invasive breast cancer. Thus, Id-1 presents a possible therapeutic antitumor target molecule in ER-negative and node-positive breast cancer.

  11. Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats.

    PubMed

    Zhang, Q L; Li, J P; Li, Y M; Chang, Q; Chen, Y; Jiang, H Z; Zhao, Z H; Guo, D

    2013-12-10

    Vascular endothelial growth factors (VEGFs) play important roles in neovascularization, tissue development, and angiogenesis. In this study, changes in VEGF expression patterns and microvessel density (MVD), and their correlations, were investigated during hair follicle development in epidermal appendages of Liaoning cashmere goats. Polyclonal antibodies to VEGF and microvessels were used for monthly immunohistochemical examinations of normal skin specimens from adult female goats for one year. VEGF was expressed in the hair bulb of primary and secondary hair follicles, the outer and inner root sheaths, sebaceous glands (ductal and secretory portions), eccrine sweat glands (ductal and secretory portions), and the epidermis. Abundant expression of VEGF was observed in the follicular basement membrane zone surrounding the bulb matrix and in ductal and secretory portions of eccrine sweat glands. The change in VEGFs in primary hair follicles showed a bimodal pattern, with the first peak observed from March to May, and the second in August. Maximal expression in secondary hair follicles occurred in May and August. Therefore, VEGF expression in primary and secondary hair follicles is synchronized throughout the year, and is correlated to hair development. In the later telogen and anagen phases, VEGF expression was higher in the secondary, compared to the primary, hair follicle. Changes in MVD also showed a bimodal pattern with peaks in May and August. VEGF expression and MVD showed moderate and strongly positive correlation in the primary and secondary hair follicles, respectively. Therefore, MVD and VEGF are closely related to the processes involved in hair cycle regulation.

  12. Synthesis of oxadiazole-morpholine derivatives and manifestation of the repressed CD31 Microvessel Density (MVD) as tumoral angiogenic parameters in Dalton's Lymphoma.

    PubMed

    Al-Ghorbani, Mohammed; Vigneshwaran, V; Ranganatha, V Lakshmi; Prabhakar, B T; Khanum, Shaukath Ara

    2015-06-01

    A series of oxadiazole derivatives possessing morpholine 6a-l were synthesized by nucleophilic substitution reaction of key intermediates [1,3,4]-oxadiazole-2-thiol derivatives 5a-l with 4-(2-chloroethyl) morpholine. Compounds 6a-l were evaluated for their in vitro and in vivo antitumor potential in Dalton's Lymphoma Ascites (DLA) tumor cells. Among 6a-l series, compound 6a with concentration ∼8.5μM have shown extensive cytotoxicity in vitro and 85% reduction in tumor volume in vivo, attributing an excellent anti-proliferative capability towards the cancer cells. Compound 6a has extensively inhibited the Microvessel Density (MVD) or tumoral neovasculature which was evident from the CD31 immuno staining and peritoneal H&E staining. The major reason for the antiproliferative activity of compound 6a was due to the repression of tumor vasculature.

  13. Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma.

    PubMed

    Guo, Yong; Xia, Peng; Zheng, Jian-Jian; Sun, Xian-Bin; Pan, Xiao-Dong; Zhang, Xing; Wu, Cun-Zao

    2015-07-01

    The receptor for advanced glycation end products (RAGE) is involved in a variety of biological processes, including tumorigenisis. Previous studies have demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule - vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were used to explore the RAGE and VEGFR-2 gene expression levels and the protein of VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi-quantification of endothelial cell marker CD34 combined with caldesmon, which was detected by microvessel density (MVD) technique and immunohistochemistry. Tumors were classified as low or high RAGE-expressing using the median as the cut-off. Immunofluorescence staining for RAGE protein was performed as well. Additionally, the median gene expression levels of VEGFR-2 in the tumors were significantly lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28-0.39) compared to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29-0.61), (P=0.03). The median MVD was significantly lower in the tumors expressing low levels of RAGE, 6.5 (95% CI, 6.21-7.43), compared to the expressing high levels, 7.9 (95% CI, 6.25-8.93), (P<0.01). Further, a positive association was certified with VEGFR-2 protein levels, P=0.07. Besides, RCC with high levels of RAGE expression are associated with high VEGFR-2 mRNA/protein levels and a higher density of microvessels; conversely, Kaplan-Meier survival analysis suggests that a significant correlation of elevated RAGE expression with decreased overall survival and metastasis-free survival. Our results establish that RAGE was identified as a potential prognostic biomarker for disease prognosis of RCC. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Canine mammary carcinomas: influence of histological grade, vascular invasion, proliferation, microvessel density and VEGFR2 expression on lymph node status and survival time.

    PubMed

    Diessler, M E; Castellano, M C; Portiansky, E L; Burns, S; Idiart, J R

    2017-06-01

    Spontaneous invasive non-inflammatory canine mammary carcinomas (CMC) and their regional lymph nodes (LN) were analysed (n = 136). Histological grade (HG) and vascular invasion (VI) in the tumours and lymph node status were recorded. Proliferation index (PI), microvessel density (MVD) and vascular endothelial growth factor receptor 2 (VEGFR2) expression were estimated using anti-proliferating cell nuclear antigen (PCNA), anti-von Willebrand factor and anti-Flk-1, respectively. Eighteen months follow-up was performed (34 bitches). Tumours of different grades showed differences regarding PI, Flk-1/integrated optical density (Flk-1/IOD) and MVD. Every feature showed significant association with LN status through bivariate analyses. From multivariate analyses, VI and Flk-1/IOD were selected to predict LN status. Data revealed that the probability of a CMC-bearing bitch to remain alive at 1, 4, 5 and 14-18 months was 0.91, 0.87, 0.81 and 0.77, respectively. Besides LN status, VI was the only feature positively correlated with survival time, although a trend to shorter survival of animal patients bearing high expressing VEGFR2 CMC was noted. © 2016 John Wiley & Sons Ltd.

  15. Lymphatic microvessel density as a predictive marker for the recurrence time of pterygium: A three-year follow-up study

    PubMed Central

    Lin, Haotian; Luo, Lixia; Ling, Shiqi; Chen, Wan; Liu, Zhaochuan; Zhong, Xiaojian; Wu, Changrui; Liu, Yizhi

    2013-01-01

    Purpose To investigate whether lymphatic microvessel density (LMVD) could be used as a predictive marker for the recurrence time of pterygia. Methods This was a prospective case series study. Ninety-six patients with unilateral eye primary nasal pterygia were included. The patients were clinically evaluated to grade the severity of their pterygia (32 were Grade 1, 29 were Grade 2, and 35 were Grade 3) before they underwent bare sclera resection with the use of mitomycin C. Excised tissues from the 96 patients and the ten normal nasal conjunctiva obtained from age-matched donor eyeballs (controls) were immunostained with LYVE-1 and CD31 monoclonal antibodies to evaluate LMVD and blood microvessel density (BMVD). The patients were followed up for three years or until pterygium recurrence was identified, which was defined as fibrovascular regrowth past the limbus in a previously compromised area. The recurrence time (RT) for a pterygium was calculated, and its relationship with LMVD and/or BMVD was statistically analyzed. Results In total, there were 24 cases of pterygium recurrence. The recurrence rate of Grade 1 was 28.1% (9/32), Grade 2 was 24.1% (7/29), and Grade 3 was 22.9% (8/35), as classified in the primary pterygium (p>0.05); the overall recurrence rate was 25% (24/96) for all patients during the three-year follow-up. In the tissue analysis, there were a small number of CD31 (+), LYVE-1(-) BMVD and only a few CD31 (weak), LYVE-1(+) LMVD in the ten normal nasal conjunctiva tissues. BMVD and LMVD increased significantly in the pterygium tissue compared to the control tissue and were significantly correlated with the width and area of pterygium in Grades 1–3 (all p values <0.05). RT was not correlated with BMVD or pterygium grade, but LMVD was significantly and negatively correlated with RT within each group and in the total patient cohort. Furthermore, we determined that an LMVD greater than 20 in the surgical specimens predicted pterygium recurrence

  16. Clinicopathological significance of BGP expression in non-small-cell lung carcinoma: relationship with histological type, microvessel density and patients' survival.

    PubMed

    Lee, Min Ki; Kim, Jae Ho; Lee, Chang Hun; Kim, Jong Min; Kang, Chi Duk; Kim, Young Dae; Choi, Kyung Un; Kim, Hwal Woong; Kim, Jee Yeon; Park, Do Youn; Sol, Mee Young

    2006-12-01

    Brain-type glycogen phosphorylase (BGP) is the major isoform of glycogen phosphorylase found in fetal and neoplastic tissues, and is generally thought to induce glucose supply during an ischaemic period. This study was performed to investigate BGP expression in non-small-cell lung carcinoma (NSCLC). A total of 119 cases of NSCLC, including 63 squamous cell carcinomas (SqCCs) and 56 adenocarcinomas (ACs), were imunohistochemically evaluated for BGP expression, and its expression was correlated with clinicopathological parameters. In total, 76.5% were positive, while non-neoplastic bronchial epithelial cells were weakly positive and pneumocytes were negative. High BGP expression was noted in 78.6% of ACs and 36.5% of SqCCs (p=0.001). Microvessel density was higher in the low BGP expression tumours (29.6 +/- 16.9/mm(2)) than in the high expression tumours (22.8+/-13.8/mm(2)) (p=0.017). BGP expression did not correlate with patient age or tumour stage, but was more frequent in females than males. Kaplan-Meier analysis showed that high BGP expression was associated with poorer survival (p=0.032). BGP is expressed in NSCLC, particularly AC, and is an independent poor prognostic factor.

  17. Number of circulating endothelial progenitor cells and intratumoral microvessel density in non-small cell lung cancer patients: differences in angiogenic status between adenocarcinoma histologic subtypes.

    PubMed

    Maeda, Ryo; Ishii, Genichiro; Ito, Masami; Hishida, Tomoyuki; Yoshida, Junji; Nishimura, Mitsuyo; Haga, Hironori; Nagai, Kanji; Ochiai, Atsushi

    2012-03-01

    Angiogenesis plays a significant role in tumor progression. This study examined the association between the number of circulating endothelial progenitor cells (EPCs), intratumoral microvessel density (MVD) (both of which may be markers for neovascularization), and lung cancer histological types, particularly adenocarcinoma histological subtypes. A total of 83 stage I non-small cell lung cancer (NSCLC) patients underwent complete tumor resection between November 2009 and July 2010. The number of EPCs from the pulmonary artery of the resected lungs was measured by assaying CD34/vascular endothelial growth factor receptor 2 positive cells, and the MVD was assessed immunohistochemically in tumor specimens by staining for CD34. A statistically significant correlation between the number of EPCs from pulmonary artery and intratumoral MVD was found (p < 0.001). No statistically significant differences in the number of EPCs and the MVD were observed between the adenocarcinomas and the squamous cell carcinomas. Among the adenocarcinoma histological subtypes, a higher number of EPCs and MVD were found significantly more frequently in solid adenocarcinomas than in nonsolid adenocarcinomas (p < 0.001 and p = 0.011, respectively). In addition, solid adenocarcinomas showed higher levels of vascular endothelial growth factor using quantitative real-time polymerase chain reaction in the tumor tissue samples than in the nonsolid adenocarcinomas (p = 0.005). The higher number of circulating EPCs and the MVD of solid adenocarcinoma may indicate the presence of differences in the tumor angiogenic status between early-stage adenocarcinoma histological subtypes. Among adenocarcinoma patients, patients with solid adenocarcinoma may be the best candidates for antiangiogenic therapies.

  18. Prognostic significance of COX-2 expression and correlation with Bcl-2 and VEGF expression, microvessel density, and clinical variables in classical Hodgkin lymphoma.

    PubMed

    Koh, Young Wha; Park, Chansik; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2013-08-01

    Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) play important roles in tumor angiogenesis. Recent reports found that COX-2 expression had prognostic value in classical Hodgkin lymphoma (cHL). The purpose of this study was to measure the expression of COX-2, B-cell lymphoma-2 (Bcl-2), VEGF, and CD31 and assess their prognostic significance and potential correlation with clinical variables in cHL. A total of 167 cHL specimens were evaluated retrospectively by immunohistochemical methods for COX-2, Bcl-2, and VEGF expression and for CD31 to measure the microvessel density (MVD). Correlations between COX-2, Bcl-2, VEGF, MVD, and clinicopathologic factors were assessed, and prognostic significance was determined. COX-2, Bcl-2, and VEGF were expressed in 27.5%, 8.3%, and 33.5% of the specimens, respectively. A positive correlation was found between COX-2 and VEGF expression (P<0.001). The MVD was significantly higher in tumors positive for both COX-2 and VEGF compared with that in tumors negative for both markers (P=0.047). COX-2 expression was associated with a lower overall survival rate (P=0.015). High MVD was associated with a lower event-free survival rate (P=0.014). COX-2 was an independent prognostic factor for overall survival on multivariate analysis (P=0.013). COX-2 and VEGF correlated with angiogenesis and tumor progression in cHL. The findings support targeting COX-2 as a potential new therapeutic approach in cHL.

  19. The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas.

    PubMed

    Jelicic, Jelena; Balint, Milena Todorovic; Jovanovic, Maja Perunicic; Boricic, Novica; Micev, Marjan; Stojsic, Jelena; Antic, Darko; Andjelic, Bosko; Bila, Jelena; Balint, Bela; Pavlovic, Sonja; Mihaljevic, Biljana

    2016-07-01

    Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p < 0.05). In DLBCL, MVD > 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p < 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p < 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).

  20. AB112. Expression of brain-specific angiogenesis inhibitor 1 and association with p53, microvessel density and vascular endothelial growth factor in the tissue of human bladder transitional cell carcinoma

    PubMed Central

    Tian, Dawei; Hu, Hailong; Wu, Changli

    2016-01-01

    Objective Brain-specific angiogenesis inhibitor 1 (BAI1) was initially described in 1997, and there have since been a number of studies on its expression in different types of cancer. The aim of the present study was to investigate the expression levels of BAI1 in bladder transitional cell carcinoma (BTCC) at different stages and the mechanism by which it inhibits tumor endothelial cell proliferation. Methods Normal bladder mucosa biopsy specimens were obtained as the control group, and human BTCC biopsy specimens were used as the study group. Immunohistochemical assays were used to detect the expression levels of BAI1, vascular endothelial growth factor (VEGF) and mutant p53, in addition to microvessel density (MVD) in the tissues. Western blotting was used to analyze the differential expression of BAI1 in the two samples. Results Statistical analysis was performed, which indicated that BAI1 expression levels in the normal bladder mucosa group were significantly higher than those in the BTCC group and were associated with clinical staging. BAI1 levels in the T1 stage BTCC tissues were higher than those in the T2–4 stage BTCC tissues (P<0.05). BAI1 expression levels were negatively correlated with those of VEGF (r=−0.661, P<0.001), mutant p53 (r=−0.406, P=0.002) and with the MVD (r=−0.675, P<0.001). Conclusions BAI1 may be involved in the negative regulation of BTCC microvascular proliferation, and its expression may be associated with a reduction in p53 mutations.

  1. Combining dynamic contrast enhanced magnetic resonance imaging and microvessel density to assess the angiogenesis after PEI in a rabbit VX2 liver tumor model.

    PubMed

    Chen, Juan; Qian, Ting; Zhang, Huanhuan; Wei, Chunxiao; Meng, Fanhua; Yin, Huabin

    2016-02-01

    To evaluate the correlation between parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and microvessel density (MVD) measurements in rabbit VX2 liver tumor models after percutaneous ethanol injection (PEI) and to observe influence of PEI on angiogenesis in a rabbit VX2 liver tumor model with dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Forty five New Zealand white rabbits were used in this study. VX2 tumor tissue blocks were implanted in the left lobe of liver by percutaneous puncture under CT guidance. 2 weeks later, all rabbits underwent conventional MRI (T1WI, T2WI) to determine the successful models. Then those successful implanted VX2 liver tumor models in the study were randomly divided into the control group and the experimental group, the former did not have processing, and the latter underwent PEI under CT guidance. MRI (T1WI, T2WI and DCE-MRI) was performed 1 week later again, the parameters of DCE-MRI (Ktrans, Kep, Ve and iAUC60) of viable tumor portions were observed. Then all the liver samples were processed for hematoxylin and eosin (H&E) staining and immunohistochemical staining for CD31 to determine MVD. At last, data (including DCE-MRI perfusion parameters and MVD) were compared between experimental and control groups, correlation of DCE-MRI perfusion parameters and MVD was evaluated. Twenty six VX2 liver tumor models underwent all examinations (thirteen models for each group) 1 week later after PEI. For the experimental group, the parameters Ktrans (r=0.6382, P=0.0189) and iAUC60 (r=0.6591, P=0.0143) in viable tumor portions were positively moderately correlated with MVD, whereas the parameters Kep (r=0.4656, P=0.1088) and Ve (r=0.2918, P=0.3333) were not correlated with MVD. For the control group, the parameters Ktrans (r=0.6385, P=0.0188) and iAUC60 (r=0.6391, P=0.0187) in viable tumor portions were also positively moderately correlated with MVD, while the parameters Kep (r=0.5518, P=0.0506) and Ve (r

  2. Adrenergic receptors on cerebral microvessels in control and Parkinsonian subjects

    SciTech Connect

    Cash, R.; Lasbennes, F.; Sercombe, R.; Seylaz, J.; Agid, Y.

    1985-08-12

    The binding of adrenergic ligands (/sup 3/H-prazosin, /sup 3/H-clonidine, /sup 3/H-dihydroalprenolol) was studied on a preparation of cerebral microvessels in the prefrontal cortex and putamen of control and Parkinsonian subjects. The adrenergic receptor density in microvessels of control patients was less than 0.5% and 3.3% respectively of the total binding. A significant decrease in the number of alpha-1 binding sites was observed on microvessels in the putamen of patients with Parkinson's disease. 22 references, 2 tables.

  3. The Local HIF-2α/EPO Pathway in the Bone Marrow is Associated with Excessive Erythrocytosis and the Increase in Bone Marrow Microvessel Density in Chronic Mountain Sickness

    PubMed Central

    Su, Juan; Cui, Sen; Ji, Linhua; Geng, Hui; Chai, Kexia; Ma, Xiaojing; Bai, Zhenzhong; Yang, Yingzhong; Wuren, Tana; Ge, Ri-Li; Rondina, Matthew T.

    2015-01-01

    Abstract Juan Su, Zhanquan Li, Sen Cui, Linhua Ji, Hui Geng, Kexia Chai, Xiaojing Ma, Zhenzhong Bai, Yingzhong Yang, Tana Wuren, Ri-Li Ge, and Matthew T. Rondina. The local HIF-2α/EPO pathway in the bone marrow is associated with excessive erythrocytosis and the increase in bone marrow microvessel density in chronic mountain sickness. High Alt Med Biol. 16:318–330, 2015.—Aim: Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis, and angiogenesis may be involved in the pathogenesis of this disease. The bone marrow niche is the primary site of erythropoiesis and angiogenesis. This study was aimed at investigating the associations of the levels of hypoxia-inducible factors (HIFs), erythropoietin (EPO), and erythropoietin receptor (EPOR), as well as microvessel density (MVD) in the bone marrow with CMS. Results: A total of 34 patients with CMS and 30 control subjects residing in areas at altitudes of 3000–4500 m were recruited for this study. The mRNA and protein expression of HIF-2α and EPO in the bone marrow cells was significantly higher in the CMS patients than in the controls. Moreover, changes in HIF-2α expression in CMS patients were significantly correlated with EPO and hemoglobin levels. In contrast, the expression of mRNA and protein expression of HIF-1α and EPOR did not differ significantly between the CMS and control patients. Increased MVD was observed in the bone marrow of the patients with CMS and it was significantly correlated with hemoglobin. Conclusions: Bone marrow cells of CMS patients may show enhanced activity of the HIF-2α/EPO pathway, and EPO may regulate the erythropoiesis and vasculogenesis through autocrine or/and paracrine mechanisms in the bone marrow niche. The increased MVD in the bone marrow of CMS patients appears to be involved in the pathogenesis of this disease. PMID:26625252

  4. Prognostic Value of Microvessel Density in Tumor and Peritumoral Area as Evaluated by CD31 Protein Expression and Argyrophilic Nucleolar Organizer Region Count in Endothelial Cells in Uterine Leiomyosarcoma

    PubMed Central

    Avdalyan, Ashot; Bobrov, Igor; Klimachev, Vladimir; Lazarev, Alexander

    2012-01-01

    The objective of this study was to investigate the prognostic value of microvessel density (MVD) in uterine leiomyosarcoma (LMS) and peritumoral area (PA) as evaluated by CD31 expression and argyrophilic nucleolar organizer region (AgNOR) count in endothelial cells. Tissue specimens from 66 patients with uterine LMS were examined. There were no significant differences in the mean MVD between tumor itself and the PA (P = 0.9); moreover, the MVD in the PA often exceeded that in the tumor. No correlation or significant differences were also found in the MVD between different grades of malignancy of LMS (r = 0.1; P = 0.07). The number of AgNORs in tumor endothelial cells was significantly higher in tumor vessels than in the peritumoral area (P < 0.005) and increased with the tumor grade. Analysis of the prognostic value of MVD in uterine LMS and PA showed that the density of tumor vessels was not an independent criterion, while the MVD in the PA affected 10-year survival to a significantly greater extent (χ 2 = 27.5; P = 0.0003). The number of AgNORs also had an important effect on survival of LMS patients: when the threshold of 11.6 granules was exceeded, prognosis was significantly more unfavorable than that prior to exceeding the threshold. PMID:22910809

  5. Fibroblast Growth Factor Receptor 1 (FGFR1), Partly Related to Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Microvessel Density, is an Independent Prognostic Factor for Non-Small Cell Lung Cancer

    PubMed Central

    Pu, Dan; Liu, Jiewei; Li, Zhixi; Zhu, Jiang; Hou, Mei

    2017-01-01

    Background This study aimed to explore the correlation between FGFR1 and clinical features, including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). FGFR1 gene amplification has been found in non-small cell lung cancer (NSCLC). However, the prognostic value of FGFR1 and the correlation between FGFR1 and clinical features are still controversial. Material/Methods A total of 92 patients with NSCLC who underwent R0 resection between July 2006 and July 2008 were enrolled in the study. The expression of FGFR1, VEGFR2, and CD34 was detected by immunohistochemistry. The correlations between the aforementioned markers and the patients’ clinical features were analyzed by the chi-square test. The impact factors of prognosis were evaluated by Cox regression analyses. Results The expression ratios of FGFR1 and VEGFR2 were 26.1% and 43.4%, respectively. The intensity of FGFR1 expression was related to VEGFR2 and histopathology. To some extent, the average microvessel density (MVD) had correlation to the expression of FGFR1 and VGEFR2. The pathological stages III–IV and high expression of FGFR1 were found to be independent prognostic factors. Conclusions The expression intensity of FGFR1 and VEGFR2 was associated with MVD, and the expression of FGFR1 is one of the independent prognostic indicators for NSCLC. PMID:28088809

  6. Microvessel basement membrane reduplication is not associated with repeated nerve fiber degeneration and regeneration.

    PubMed

    Baker, M K; Bourque, P; Dyck, P J

    1996-03-01

    To determine whether repeated nerve fiber degeneration and regeneration can induce reduplication of endoneurial microvessel basement membranes (BMs), typical of such conditions as diabetic polyneuropathy, electronmicrographs of endoneurial microvessels of rat peroneal and tibial nerves were studied in repeatedly crushed (10 x) sciatic nerves and compared to microvessels of sham-operated uncrushed nerves. On average, crushed nerves had 2.6, SE +/- 0.1 BMs, whereas control nerves had 2.7, SE +/- 0.1 (P > 0.05). Microvessel cellular components were significantly increased in both number and size in the crushed nerves. These nerves also demonstrated a trend to increased vessel numbers and density. These results are not in keeping with the hypothesis that BM reduplication of endoneurial microvessels is simply due to repeated fiber degeneration and regeneration.

  7. Tobacco Retail Outlet Density and Young Adult Tobacco Initiation

    PubMed Central

    Pearson, Jennifer L.; Anesetti-Rothermel, Andrew; Xiao, Haijun; Kirchner, Thomas R.; Vallone, Donna

    2016-01-01

    Background: A growing body of evidence indicates that the density of tobacco retail outlets around the home residence may influence tobacco use among youth and adults. The purpose of this study was to examine the impact of neighborhood tobacco retail outlet density on young adult initiation of different tobacco product types. Methods: Cross-sectional data from a 2013 nationally representative sample of young adults aged 18–34 was examined in relation to a 2012 geocoded listing of all outlets likely to sell tobacco in the United States. Separate multivariable logistic regression analyses examined associations between neighborhood outlet density and past 6 months first use of cigarettes, non-cigarette combustible products, and noncombustible products among adults aged 18–24 and 25–34. Results: Outlet density was significantly associated with recent initiation of cigarettes and other combustibles, but this impact varied for younger and older groups. Increased density was significantly associated with a higher likelihood of initiating cigarette use among adults aged 25–34 (OR = 3.75, 95% CI = 1.18, 11.90), and of initiating non-cigarette combustible use among 18–24 year olds (OR = 3.16, 95% CI = 1.03, 9.74). There was no impact of outlet density on recent noncombustible product initiation among either group. Conclusion: This study is the first to examine the impact of tobacco outlet density on young adult initiation of cigarettes and other tobacco products. Findings demonstrate that residential neighborhood outlet density is associated with recent initiation of combustible products and this effect varies by product type and age. The tobacco outlet environment may be a critical factor in promoting young adult tobacco use initiation. PMID:25666816

  8. Transurethral Resection of Prostate and Bleeding: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial to See the Efficacy of Short-Term Use of Finasteride and Dutasteride on Operative Blood Loss and Prostatic Microvessel Density.

    PubMed

    Bansal, Ankur; Arora, Aditi

    2017-09-01

    The aim of this study was to determine the efficacy of short-duration use of finasteride and dutasteride before transurethral resection of the prostate (TURP) on intraoperative blood loss and microvessel density (MVD) of prostate stroma and suburethral tissues in benign prostatic hyperplasia (BPH). This study includes 450 patients who were planned for TURP. They were prospectively randomized into three groups (150 patients each). Group 1 received placebo, group 2 received finasteride, 5 mg per day, and group 3 patients received dutasteride, 0.5 mg per day, for 4 weeks before surgery. The total blood loss, requirement of blood, and MVDs in prostate stroma and suburethral tissues were calculated in each patient and then compared among three groups. There was significant reduction in mean blood loss, blood loss/time, and total blood loss per gram of resected tissue in finasteride and dutasteride groups compared with placebo. Prostate stromal and suburethral MVDs were significantly higher compared with placebo. Blood transfusion was required in 9.3%, 2.7%, and 2% of the patients, respectively (p = 0.004). However, no statistically significant differences were observed between finasteride and dutasteride groups for these parameters (p > 0.05). The weight of resected prostate, operating time, and amount of irrigation fluid used did not show any significant difference between the three groups. Short-term pretreatment with finasteride and dutasteride has similar efficacy and significantly reduces perioperative bleeding during TURP and has minimal negative impact on sexual function. According to our findings, a 4-week prior administration of 5-alpha-reductase inhibitors may reduce operative blood loss and prostatic MVD in TURP, thus potentially decreasing blood loss-related complications and the requirement of blood transfusion.

  9. In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts

    PubMed Central

    McCormack, Devin R.; Walsh, Alex J.; Sit, Wesley; Arteaga, Carlos L.; Chen, Jin; Cook, Rebecca S.; Skala, Melissa C.

    2014-01-01

    HER2-amplified (HER2 + ) breast cancers are treated with the anti-HER2 monoclonal antibody trastuzumab. Although trastuzumab reduces production of the angiogenic factor VEGF in HER2 + tumors, the acute and sustained effects of trastuzumab on the tumor vasculature are not understood fully, particularly in trastuzumab-resistant tumors. We used mouse models of trastuzumab sensitive and trastuzumab-resistant HER2 + breast cancers to measure dynamic changes in tumor microvessel density and hemoglobin oxygenation (sO2) in vivo using quantitative hyperspectral imaging at 2, 5, 9, and 14 days after antibody treatment. Further analysis quantified the distribution of microvessels into low and high oxygenation groups, and monitored changes in these distributions with trastuzumab treatment. Gold standard immunohistochemistry was performed to validate complementary markers of tumor cell and vascular response to treatment. Trastuzumab treatment in both responsive and resistant tumors resulted in decreased sO2 5 days after initial treatment when compared to IgG-treated controls (p<0.05). Importantly, responsive tumors showed significantly higher vessel density and significantly lower sO2 than all other groups at 5 days post-treatment (p<0.05). Distribution analysis of vessel sO2 showed a significant (p<0.05) shift of highly oxygenated vessels towards lower oxygenation over the time-course in both trastuzumab-treated responsive and resistant tumors. This study suggests that longitudinal hyperspectral imaging of microvessel sO2 and density could distinguish trastuzumab-responsive from trastuzumab-resistant tumors, a finding that could be exploited in the post-neoadjuvant setting to guide post-surgical treatment decisions. PMID:25071962

  10. Three-dimensional visualization and analysis of microvessels in prostate cancer

    NASA Astrophysics Data System (ADS)

    Kay, Paul A.; Robb, Richard A.; Bostwick, David G.; Leske, David A.; Camp, Jon J.

    1995-05-01

    A significant increase in diagnostic incidence of prostate cancer underscores the need to accurately stratify and quantify the cancers to facilitate appropriate therapy. Currently, there is no reliable method to preoperatively predict pathological stage and thus malignant potential of prostate cancer. Tumor volume and microvessel density have been shown postoperatively to be accurate predictors of cancer metastatic potential. 3D visualization and analysis of image volumes produced from series of immunocytochemically stained pathological sections may improve our understanding of the relationships of the tumor to angiogenesis, i.e., to the microvessel density of the tumor. Sequential thinly sliced (approximately 7 microns) pathological sections of the prostate will be differentially stained with fluorescent antibodies to clotting factor VIII- related antigen, which labels the endothelial cells of the vessels, facilitating automated color separation for visualization of the microvessels. Digitized images of the sections can be synthesized into 3D volumes and measured to quantify vessel quantity and density. Using 3D colorwash and transparency display techniques, anatomic and densitrometric relationships between the tumor and microvessels can be visualized. The microvessel density can be measured using image processing algorithms and compared to measurements made by pathologists. Advanced approaches to imaging the prostate in vivo include dynamic MRI techniques using contrast agents to accurately detect and quantify the region of prostate cancer. The cancerous region can be correlated with histologic specimens using the same methods described for measurement of microvessel density. This detailed information could lead to improved methods to properly stratify patients with diagnosed prostate cancer.

  11. Probe initial parton density and formation time via jet quenching

    SciTech Connect

    Wang, Xin-Nian

    2002-09-20

    Medium modification of jet fragmentation function due to multiple scattering and induced gluon radiation leads directly to jet quenching or suppression of leading particle distribution from jet fragmentation. One can extract an effective total parton energy loss which can be related to the total transverse momentum broadening. For an expanding medium, both are shown to be sensitive to the initial parton density and formation time. Therefore, one can extract the initial parton density and formation time from simultaneous measurements of parton energy loss and transverse momentum broadening. Implication of the recent experimental data on effects of detailed balance in parton energy loss is also discussed.

  12. Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo

    PubMed Central

    Fu, Bingmei M.; Yang, Jinlin; Cai, Bin; Fan, Jie; Zhang, Lin; Zeng, Min

    2015-01-01

    Tumor cell adhesion to the microvessel wall is a critical step during tumor metastasis. Vascular endothelial growth factor (VEGF), a secretion of tumor cells, can increase microvessel permeability and tumor cell adhesion in the microvessel. To test the hypothesis that inhibiting permeability increase can reduce tumor cell adhesion, we used in vivo fluorescence microscopy to measure both microvessel permeability and adhesion rates of human mammary carcinoma MDA-MB-231 cells in post-capillary venules of rat mesentery under the treatment of VEGF and a cAMP analog, 8-bromo-cAMP, which can decrease microvessel permeability. By immunostaining adherens junction proteins between endothelial cells forming the microvessel wall, we further investigated the structural mechanism by which cAMP abolishes VEGF-induced increase in microvessel permeability and tumor cell adhesion. Our results demonstrate that 1) Pretreatment of microvessels with cAMP can abolish VEGF-enhanced microvessel permeability and tumor cell adhesion; 2) Tumor cells prefer to adhere to the endothelial cell junctions instead of cell bodies; 3) VEGF increases microvessel permeability and tumor cell adhesion by compromising endothelial junctions while cAMP abolishes these effects of VEGF by reinforcing the junctions. These results suggest that strengthening the microvessel wall integrity can be a potential approach to inhibiting hematogenous tumor metastasis. PMID:26507779

  13. Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo

    NASA Astrophysics Data System (ADS)

    Fu, Bingmei M.; Yang, Jinlin; Cai, Bin; Fan, Jie; Zhang, Lin; Zeng, Min

    2015-10-01

    Tumor cell adhesion to the microvessel wall is a critical step during tumor metastasis. Vascular endothelial growth factor (VEGF), a secretion of tumor cells, can increase microvessel permeability and tumor cell adhesion in the microvessel. To test the hypothesis that inhibiting permeability increase can reduce tumor cell adhesion, we used in vivo fluorescence microscopy to measure both microvessel permeability and adhesion rates of human mammary carcinoma MDA-MB-231 cells in post-capillary venules of rat mesentery under the treatment of VEGF and a cAMP analog, 8-bromo-cAMP, which can decrease microvessel permeability. By immunostaining adherens junction proteins between endothelial cells forming the microvessel wall, we further investigated the structural mechanism by which cAMP abolishes VEGF-induced increase in microvessel permeability and tumor cell adhesion. Our results demonstrate that 1) Pretreatment of microvessels with cAMP can abolish VEGF-enhanced microvessel permeability and tumor cell adhesion; 2) Tumor cells prefer to adhere to the endothelial cell junctions instead of cell bodies; 3) VEGF increases microvessel permeability and tumor cell adhesion by compromising endothelial junctions while cAMP abolishes these effects of VEGF by reinforcing the junctions. These results suggest that strengthening the microvessel wall integrity can be a potential approach to inhibiting hematogenous tumor metastasis.

  14. Mechanics and computational simulation of blood flow in microvessels

    PubMed Central

    Secomb, Timothy W.

    2010-01-01

    Blood is a concentrated suspension of red blood cells (RBCs). Motion and deformation of RBCs can be analyzed based on knowledge of their mechanical characteristics. Axisymmetric models for single-file motion of RBCs in capillaries yield predictions of apparent viscosity in good agreement with experimental results for diameters up to about 8 micron. Two-dimensional simulations, in which each RBC is represented as a set of interconnected viscoelastic elements, predict that off-centre RBCs in an 8-micron channel take asymmetric shapes and drift toward the centre-line. Predicted trajectories agree with observations in microvessels of the rat mesentery. An isolated RBC initially positioned near the wall of a 20-micron channel is deformed into an asymmetric shape, migrates away from the wall, and then enters a complex tumbling motion with continuous shape change. Realistic simulation of multiple interacting RBCs in microvessels remains as a major challenge. PMID:21036096

  15. Shockwave compression of Argon gas at several initial densities

    NASA Astrophysics Data System (ADS)

    Dattelbaum, Dana; Goodwin, Peter; Garcia, Daniel; Gustavsen, Richard; Lang, John; Aslam, Tariq; Sheffield, Stephen; Gibson, Lloyd; Morris, John; Los Alamos National Laboratory Team

    2015-06-01

    Experimental data of the principal Hugoniot locus of gas-phase noble gases are rare. The majority of Hugoniot data is either from shock tube experiments on low-pressure gases or from plate impact experiments on cryogenic, liquefied gases. In both cases, physics regarding shock compressibility, thresholds for the on-set of ionization, and dissociation chemistry are difficult to infer for gases at intermediate densities. We have developed an experimental target for gas gun-driven plate impact experiments on gases at initial pressures between 200-1000 psi. Using optical velocimetry, we directly determine shock and particle velocities on the principal Hugoniot locus, as well as clearly differentiate ionization thresholds. The target design also results in multiply shocking the gas in a quasi-isentropic fashion yielding off-Hugoniot compression data. Using an impactor with higher impedance than the drive plate, we are able to achieve initial particle velocities well in excess of the impactor velocities. We will describe the results of plate impact experiments on Ar with initial densities between 0.02-0.05 g/cm3. By coupling optical fibers to the targets, we have measured the time-resolved optical emission, spectrally-resolved with a spectrometer coupled to an optical streak camera, and with a 5-color optical pyrometer for temperature determination. The experimental results are compared with hydrodynamic simulations using ideal gas and Sesame tabular equations of state.

  16. Relationship between Exploding Bridgewire & Spark Initiation of Low Density PETN

    NASA Astrophysics Data System (ADS)

    Lee, Elizabeth; Drake, Rod

    2015-06-01

    Recent work has shown that the energy delivered after bridgewire burst affects the function time of an EBW detonator. The spark which is formed post bridgewire burst is the means by which the remaining fireset energy is delivered into the detonator. Therefore, by studying the characteristics of spark-gap detonators insight into the contribution of spark initiation to the functioning of EBW detonators may be achieved. Spark initiation of low density explosives consists of; (i) spark formation, (ii) spark interaction with the bed, and (iii) ignition and growth of reaction. Experiments were performed in which beds of an inert simulant were used to study the formation and propagation of sparks. The effect of the spark on inert porous beds was studied over a limited delivered energy range. The disruption of the bed was found to be dependent on the particle size / pore structure of the bed. The effect of spark initiation on a low density PETN bed was then examined, the relationship between delivered energy and function time was found to be the same as for EBW detonators. This necessitated the development of electrical diagnostic techniques to measure the energy delivered to the spark.

  17. Shockwave compression of Ar gas at several initial densities

    NASA Astrophysics Data System (ADS)

    Dattelbaum, Dana M.; Goodwin, Peter M.; Garcia, Daniel B.; Gustavsen, Richard L.; Lang, John M.; Aslam, Tariq D.; Sheffield, Stephen A.; Gibson, Lloyd L.; Morris, John S.

    2017-01-01

    Experimental data of the principal Hugoniot locus of variable density gas-phase noble and molecular gases are rare. The majority of shock Hugoniot data is either from shock tube experiments on low-pressure gases or from plate impact experiments on cryogenic, liquefied gases. In both cases, physics regarding shock compressibility, thresholds for the on-set of shock-driven ionization, and even dissociation chemistry are difficult to infer for gases at intermediate densities. We have developed an experimental target design for gas gun-driven plate impact experiments on noble gases at initial pressures between 200-1000 psi. Using optical velocimetry, we are able to directly determine both the shock and particle velocities of the gas on the principal Hugoniot locus, as well as clearly differentiate ionization thresholds. The target design also results in multiply shocking the gas in a quasi-isentropic fashion yielding off-Hugoniot compression data. We describe the results of a series of plate impact experiments on Ar with starting densities between 0.02-0.05 g/cm3 at room temperature. Furthermore, by coupling optical fibers to the targets, we have measured the time-resolved optical emission from the shocked gas using a spectrometer coupled to an optical streak camera to spectrally-resolve the emission, and with a 5-color optical pyrometer for temperature determination.

  18. Gender-specific protection from microvessel rarefaction in female hypertensive rats.

    PubMed

    Papanek, P E; Rieder, M J; Lombard, J H; Greene, A S

    1998-08-01

    Epidemiologic studies reveal that women have a significantly lower age-adjusted morbidity and mortality from cardiovascular disease than men, suggesting that gender is a cardiovascular disease risk factor. The mechanism of the "gender protection" is unknown. In this study, we investigated the microvascular remodeling in reduced renal mass plus a high salt (4.0% NaCl) diet model of hypertension (RRM + HS). We hypothesized that women would be protected from the increase in blood pressure and from the microvascular rarefaction associated with RRM + HS hypertension. Studies were designed to determine whether female rats were less susceptible to changes in microvessel density during RRM + HS. Microvessel density was measured in male and female low salt (0.4% LS) sham-operated controls (Sham + LS) and after 3 days or 4 weeks of RRM + HS hypertension. The microcirculation of hind limb (medial and lateral gastrocnemius, plantaris, soleus) muscles was visualized using rhodamine-labeled Griffonia simplicifolia I lectin. Tissue sections were examined by videomicroscopy and microvessel density was determined by quantitative stereology. As shown previously, mean arterial pressure increased to 160 +/- 8 mm Hg and microvessel density decreased (>30% decrease in all beds) in male RRM + HS. In contrast, mean arterial pressure of female RRM + HS rats was modestly increased from 101 +/- 2 to 118 +/- 4 mm Hg. Despite previous results showing a reduction in microvessel density of both normotensive and hypertensive male rats on a high salt diet, microvessel density of female RRM + HS rats was not reduced at either time. These results suggest that gender protection in the RRM rat extends beyond an attenuation of the increase in pressure to an immunity from microvascular rarefaction.

  19. Changes in endothelial connexin 43 expression inversely correlate with microvessel permeability and VE-cadherin expression in endotoxin-challenged lungs

    PubMed Central

    Kandasamy, Kathirvel; Escue, Rachel; Manna, Jayeeta; Adebiyi, Adebowale

    2015-01-01

    Endothelial barrier restoration reverses microvessel hyperpermeability and facilitates recovery from lung injury. Because inhibiting connexin 43 (Cx43)-dependent interendothelial communication blunts hyperpermeability in single microvessels, we determined whether endothelial Cx43 levels correlate with changes in microvessel permeability during recovery from lung injury. Toward this, bacterial endotoxin was instilled intratracheally into rat lungs, and at different durations postinstillation the lungs were isolated and blood perfused. Microvessel Cx43 expression was quantified by in situ immunofluorescence and microvessel permeability via a fluorescence method. To supplement the immunofluorescence data, protein levels were determined by immunoblots of lung tissue from endotoxin-instilled rats. Immunofluorescence and immunoblot together revealed that both Cx43 expression and microvessel permeability increased above baseline within a few hours after endotoxin instillation but declined progressively over the next few days. On day 5 postendotoxin, microvessel Cx43 declined to negligible levels, resulting in complete absence of intermicrovessel communication determined by photolytic uncaging of Ca2+. However, by day 14, both Cx43 expression and microvessel permeability returned to baseline levels. In contrast to Cx43, expression of microvessel vascular endothelial (VE)-cadherin, a critical determinant of vascular barrier integrity, exhibited an inverse trend by initially declining below baseline and then returning to baseline at a longer duration. Knockdown of vascular Cx43 by tail vein injection of Cx43 shRNA increased VE-cadherin expression, suggesting that reduction in Cx43 levels may modulate VE-cadherin levels in lung microvessels. Together, the data suggest that endotoxin challenge initiates interrelated changes in microvessel Cx43, VE-cadherin, and microvessel permeability, with changes in Cx43 temporally leading the other responses. PMID:26163513

  20. Changes in endothelial connexin 43 expression inversely correlate with microvessel permeability and VE-cadherin expression in endotoxin-challenged lungs.

    PubMed

    Kandasamy, Kathirvel; Escue, Rachel; Manna, Jayeeta; Adebiyi, Adebowale; Parthasarathi, Kaushik

    2015-09-15

    Endothelial barrier restoration reverses microvessel hyperpermeability and facilitates recovery from lung injury. Because inhibiting connexin 43 (Cx43)-dependent interendothelial communication blunts hyperpermeability in single microvessels, we determined whether endothelial Cx43 levels correlate with changes in microvessel permeability during recovery from lung injury. Toward this, bacterial endotoxin was instilled intratracheally into rat lungs, and at different durations postinstillation the lungs were isolated and blood perfused. Microvessel Cx43 expression was quantified by in situ immunofluorescence and microvessel permeability via a fluorescence method. To supplement the immunofluorescence data, protein levels were determined by immunoblots of lung tissue from endotoxin-instilled rats. Immunofluorescence and immunoblot together revealed that both Cx43 expression and microvessel permeability increased above baseline within a few hours after endotoxin instillation but declined progressively over the next few days. On day 5 postendotoxin, microvessel Cx43 declined to negligible levels, resulting in complete absence of intermicrovessel communication determined by photolytic uncaging of Ca(2+). However, by day 14, both Cx43 expression and microvessel permeability returned to baseline levels. In contrast to Cx43, expression of microvessel vascular endothelial (VE)-cadherin, a critical determinant of vascular barrier integrity, exhibited an inverse trend by initially declining below baseline and then returning to baseline at a longer duration. Knockdown of vascular Cx43 by tail vein injection of Cx43 shRNA increased VE-cadherin expression, suggesting that reduction in Cx43 levels may modulate VE-cadherin levels in lung microvessels. Together, the data suggest that endotoxin challenge initiates interrelated changes in microvessel Cx43, VE-cadherin, and microvessel permeability, with changes in Cx43 temporally leading the other responses.

  1. Neurotransmitter Receptor Binding in Bovine Cerebral Microvessels

    NASA Astrophysics Data System (ADS)

    Peroutka, Stephen J.; Moskowitz, Michael A.; Reinhard, John F.; Synder, Solomon H.

    1980-05-01

    Purified preparations of microvessels from bovine cerebral cortex contain substantial levels of alpha-adrenergic, beta-adrenergic, and histamine 1 receptor binding sites but only negligible serotonin, muscarinic cholinergic, opiate, and benzodiazepine receptor binding. Norepinephrine and histamine may be endogenous regulators of the cerebral microcirculation at the observed receptors.

  2. Chronic ethanol treatment changes the number of beta-receptors in rat brain microvessels

    SciTech Connect

    Lucchi, L.; Cazzaniga, A.; Picotti, G.B.; Covelli, V.; Magnoni, M.S.; Borriero, L.; Spano, P.F.; Trabucchi, M.

    1984-01-01

    The effect of chronic ethanol consumption on the binding (125I)-iodohydroxybenzylpindolol to beta-adrenergic receptors in rat brain microvessels has been studied. The results show that chronic ethanol treatment increases the number of beta-receptors present in brain microvessels without changing the binding affinity of the binding site for the beta-adrenoceptor ligand. This effect is apparently not associated with changes in peripheral adrenergic tone, since no differences in platelet epinephrine or norepinephrine concentrations were found between ethanol-treated and control animals. An increase in beta-receptor density in brain microvessels might contribute to the alterations of cerebral blood flow and oxygen consumption reported during chronic ethanol intoxication.

  3. Structural and functional bases of laser-microvessels interaction

    NASA Astrophysics Data System (ADS)

    Kozlov, Valentine I.; Terman, Oleg A.; Builin, Vitalij; Lebedeva, Natalia A.; Samoilov, Nickolai

    1993-07-01

    Structural and functional microcirculatory changes in tissues and organs (muscles, liver, derma, epinephros, brain cortex) under various dosages and powers of laser irradiation in the red (633 nm) and near infrared (890 nm) spectrum regions have been studied in experiments and clinic. In case of nonsensitized tissues the `photoactivation' range of power densities and doses of laser irradiation has been established. We have identified a short-term reaction of microvessels and a long-term reaction (adaptation). The former consists of intensification of microcirculation and metabolism rise in parenchymatous cells; the latter is connected with neoangiogenesis acceleration. The intensification of the blood microcirculation includes a dilation of microvessels of all orders, an amplification of arteriolar vasomotions and an opening of `reserved' capillaries. Data on the structural reconstruction of myocytes and endotheliocytes have shown that the high differential parenchymatous cells and its membrane structures are sensitive to low energy laser irradiation and, on the other hand, under low energy laser irradiation there is an activation of synthetic processes in the cells. Thus, during the laser-tissue interaction in such complex system as human organism the microcirculation plays the key role among the other systems.

  4. Comparison of methods for staining microvessels in bone.

    PubMed

    Jian, Yuekui; Tian, Xiaobin; Li, Qing; Li, Bo; Peng, Zhi

    2012-08-01

    Detection of microvessels is critical for studying bone tissue. We developed an intravascular ink-based method coupled with Van Gieson (VG) staining and compared it with other commonly used methods for capillary visualization. The ink perfusate was formulated as 10% ink, 10% formaldehyde and 20% mannitol. The ink solution was perfused into a healthy goat and the tibia was subjected to decalcification, dehydration, paraffin embedding, de-waxing and staining to observe microvessels. Angiogenesis was assessed by vascular area image analysis and the hematoxylin and eosin (HE), Masson, and VG staining techniques were compared to determine the reliability of these methods for counting microvessels. We found that HE, Masson, and VG staining produced poor contrast between the microvessels and surrounding tissues. By contrast, ink coupled with VG staining permitted clear discrimination between the microvessels and surrounding tissues. Our results indicate that ink-VG staining could be more useful than other methods for detecting tissue microvessels.

  5. In vivo perfusion of human skin substitutes with microvessels formed by adult circulating endothelial progenitor cells.

    PubMed

    Kung, Elaine F; Wang, Feiya; Schechner, Jeffrey S

    2008-02-01

    At present, tissue-engineered human skin substitutes (HSSs) mainly function as temporary bioactive dressings due to inadequate perfusion. Failure to form functional vascular networks within the initial posttransplantation period compromises cell survival of the graft and its long-term viability in the wound bed. Our goal was to demonstrate that adult circulating endothelial progenitor cells (EPCs) seeded onto HSS can form functional microvessels capable of graft neovascularization and perfusion. Adult peripheral blood mononuclear cells (PBMCs) underwent CD34 selection and endothelial cell (EC) culture conditions. After in vitro expansion, flow cytometry verified EC phenotype before their incorporation into HSS. After 2 weeks in vivo, immunohistochemical analysis, immunofluorescent microscopy, and microfil polymer perfusion were performed. CD34+ PBMCs differentiated into EPC demonstrating characteristic EC morphology and expression of CD31, Tie-2, and E-selectin after TNFalpha-induction. Numerous human CD31 and Ulex europaeus agglutinin-1 (UEA-1) microvessels within the engineered grafts (HSS/EPCs) inosculated with recipient murine circulation. Limitation of murine CD31 immunoreactivity to HSS margins showed angiogenesis was attributable to human EPC at 2 weeks posttransplantation. Delivery of intravenous rhodamine-conjugated UEA-1 and microfil polymer to HSS/EPCs demonstrated enhanced perfusion by functional microvessels compared to HSS control without EPCs. We successfully engineered functional microvessels in HSS by incorporating adult circulating EPCs. This autologous EC source can form vascular conduits enabling perfusion and survival of human bioengineered tissues.

  6. Shock initiation experiments with ignition and growth modeling on low density composition B

    NASA Astrophysics Data System (ADS)

    Vandersall, Kevin S.; Garcia, Frank; Tarver, Craig M.

    2017-01-01

    Shock initiation experiments on low density (˜1.2 and ˜1.5 g/cm3) Composition B were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (˜1.2 g/cm3) confined in Teflon rings or sample disks pressed to low density (˜1.5 g/cm3). The shock sensitivity was found to increase with decreasing density as expected. Ignition and Growth model parameters were derived that yielded reasonable agreement with the experimental data at both initial densities. The shock sensitivity at the tested densities are compared to prior published work with near full density material.

  7. Effects of wall shear stress and its gradient on tumor cell adhesion in curved microvessels.

    PubMed

    Yan, W W; Cai, B; Liu, Y; Fu, B M

    2012-05-01

    Tumor cell adhesion to vessel walls in the microcirculation is one critical step in cancer metastasis. In this paper, the hypothesis that tumor cells prefer to adhere at the microvessels with localized shear stresses and their gradients, such as in the curved microvessels, was examined both experimentally and computationally. Our in vivo experiments were performed on the microvessels (post-capillary venules, 30-50 μm diameter) of rat mesentery. A straight or curved microvessel was cannulated and perfused with tumor cells by a glass micropipette at a velocity of ~1mm/s. At less than 10 min after perfusion, there was a significant difference in cell adhesion to the straight and curved vessel walls. In 60 min, the averaged adhesion rate in the curved vessels (n = 14) was ~1.5-fold of that in the straight vessels (n = 19). In 51 curved segments, 45% of cell adhesion was initiated at the inner side, 25% at outer side, and 30% at both sides of the curved vessels. To investigate the mechanical mechanism by which tumor cells prefer adhering at curved sites, we performed a computational study, in which the fluid dynamics was carried out by the lattice Boltzmann method , and the tumor cell dynamics was governed by the Newton's law of translation and rotation. A modified adhesive dynamics model that included the influence of wall shear stress/gradient on the association/dissociation rates of tumor cell adhesion was proposed, in which the positive wall shear stress/gradient jump would enhance tumor cell adhesion while the negative wall shear stress/gradient jump would weaken tumor cell adhesion. It was found that the wall shear stress/gradient, over a threshold, had significant contribution to tumor cell adhesion by activating or inactivating cell adhesion molecules. Our results elucidated why the tumor cell adhesion prefers to occur at the positive curvature of curved microvessels with very low Reynolds number (in the order of 10(-2)) laminar flow.

  8. Thrombin Induces Inositol Trisphosphate-Mediated Spatially Extensive Responses in Lung Microvessels.

    PubMed

    Escue, Rachel; Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2017-04-01

    Activation of plasma membrane receptors initiates compartmentalized second messenger signaling. Whether this compartmentalization facilitates the preferential intercellular diffusion of specific second messengers is unclear. Toward this, the receptor-mediated agonist, thrombin, was instilled into microvessels in a restricted region of isolated blood-perfused mouse lungs. Subsequently, the thrombin-induced increase in endothelial F-actin was determined using confocal fluorescence microscopy. Increased F-actin was evident in microvessels directly treated with thrombin and in those located in adjoining thrombin-free regions. This increase was abrogated by inhibiting inositol trisphosphate-mediated calcium release with Xestospongin C (XeC). XeC also inhibited the thrombin-induced increase in the amplitude of endothelial cytosolic Ca(2+) oscillations. Instillation of thrombin and XeC into adjacent restricted regions increased F-actin in microvessels in the thrombin-treated and adjacent regions but not in those in the XeC-treated region. Thus, inositol trisphosphate, and not calcium, diffused interendothelially to the spatially remote thrombin-free microvessels. Thus, activation of plasma membrane receptors increased the ambit of inflammatory responses via a second messenger different from that used by stimuli that induce cell-wide increases in second messengers. Thrombin however failed to induce the spatially extensive response in microvessels of mice lacking endothelial connexin43, suggesting a role for connexin43 gap junctions. Compartmental second messenger signaling and interendothelial communication define the specific second messenger involved in exacerbating proinflammatory responses to receptor-mediated agonists.

  9. Leukocyte margination in a model microvessel

    NASA Astrophysics Data System (ADS)

    Freund, Jonathan B.

    2007-02-01

    The physiological inflammation response depends upon the multibody interactions of blood cells in the microcirculation that bring leukocytes (white blood cells) to the vessel walls. We investigate the fluid mechanics of this using numerical simulations of 29 red blood cells and one leukocyte flowing in a two-dimensional microvessel, with the cells modeled as linearly elastic shell membranes. Despite its obvious simplifications, this model successfully reproduces the increasingly blunted velocity profiles and increased leukocyte margination observed at lower shear rates in actual microvessels. Red cell aggregation is shown to be unnecessary for margination. The relative stiffness of the red cells in our simulations is varied by over a factor of 10, but the margination is found to be much less correlated with this than it is to changes associated with the blunting of the mean velocity profile at lower shear rates. While velocity around the leukocyte when it is near the wall depends upon the red cell properties, it changes little for strongly versus weakly marginating cases. In the more strongly marginating cases, however, a red cell is frequently observed to be leaning on the upstream side of the leukocyte and appears to stabilize it, preventing other red cells from coming between it and the wall. A well-known feature of the microcirculation is a near-wall cell-free layer. In our simulations, it is observed that the leukocyte's most probable position is at the edge of this layer. This wall stand-off distance increases with velocity following a scaling that would be expected for a lubrication mechanism, assuming that there were a nearly constant force pushing the cells toward the wall. The leukocyte's near-wall position is observed to be less stable with increasing mean stand-off distance, but this distance would have potentially greater effect on adhesion since the range of the molecular binding is so short.

  10. Quantification of microvessels in canine lymph nodes.

    PubMed

    Tonar, Zbynĕk; Egger, Gunter F; Witter, Kirsti; Wolfesberger, Birgitt

    2008-10-01

    Quantification of microvessels in tumors is mostly based on counts of vessel profiles in tumor hot spots. Drawbacks of this method include low reproducibility and large interobserver variance, mainly as a result of individual differences in sampling of image fields for analysis. Our aim was to test an unbiased method for quantifying microvessels in healthy and tumorous lymph nodes of dogs. The endothelium of blood vessels was detected in paraffin sections by a combination of immunohistochemistry (von Willebrand factor) and lectin histochemistry (wheat germ agglutinin) in comparison with detection of basal laminae by laminin immunohistochemistry or silver impregnation. Systematic uniform random sampling of 50 image fields was performed during photo-documentation. An unbiased counting frame (area 113,600 microm(2)) was applied to each micrograph. The total area sampled from each node was 5.68 mm(2). Vessel profiles were counted according to stereological counting rules. Inter- and intraobserver variabilities were tested. The application of systematic uniform random sampling was compared with the counting of vessel profiles in hot spots. The unbiased estimate of the number of vessel profiles per unit area ranged from 100.5 +/- 44.0/mm(2) to 442.6 +/- 102.5/mm(2) in contrast to 264 +/- 72.2/mm(2) to 771.0 +/- 108.2/mm(2) in hot spots. The advantage of using systematic uniform random sampling is its reproducibility, with reasonable interobserver and low intraobserver variance. This method also allows for the possibility of using archival material, because staining quality is not limiting as it is for image analysis, and artifacts can easily be excluded. However, this method is comparatively time-consuming.

  11. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

    PubMed

    Colbert, C M; Johnston, D

    1996-11-01

    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  12. Lateral Root Initiation in Arabidopsis: Developmental Window, Spatial Patterning, Density and Predictability

    PubMed Central

    DUBROVSKY, J. G.; GAMBETTA, G. A.; HERNÁNDEZ-BARRERA, A.; SHISHKOVA, S.; GONZÁLEZ, I.

    2006-01-01

    • Background and Aims The basic regulatory mechanisms that control lateral root (LR) initiation are still poorly understood. An attempt is made to characterize the pattern and timing of LR initiation, to define a developmental window in which LR initiation takes place and to address the question of whether LR initiation is predictable. • Methods The spatial patterning of LRs and LR primordia (LRPs) on cleared root preparations were characterized. New measures of LR and LRP densities (number of LRs and/or LRPs divided by the length of the root portions where they are present) were introduced and illustrate the shortcomings of the more customarily used measure through a comparative analysis of the mutant aux1-7. The enhancer trap line J0121 was used to monitor LR initiation in time-lapse experiments and a plasmolysis-based method was developed to determine the number of pericycle cells between successive LRPs. • Key Results LRP initiation occurred strictly acropetally and no de novo initiation events were found between already developed LRs or LRPs. However, LRPs did not become LRs in a similar pattern. The longitudinal spacing of lateral organs was variable and the distance between lateral organs was proportional to the number of cells and the time between initiations of successive LRPs. There was a strong tendency towards alternation in LR initiation between the two pericycle cell files adjacent to the protoxylem poles. LR density increased with time due to the emergence of slowly developing LRPs and appears to be unique for individual Arabidopsis accessions. • Conclusions. In Arabidopsis there is a narrow developmental window for LR initiation, and no specific cell-count or distance-measuring mechanisms have been found that determine the site of successive initiation events. Nevertheless, the branching density and lateral organ density (density of LRs and LRPs) are accession-specific, and based on the latter density the average distance between successive

  13. Remark on compressible Navier-Stokes equations with density-dependent viscosity and discontinuous initial data

    NASA Astrophysics Data System (ADS)

    Zhang, Ting; Fang, Daoyuan

    2008-03-01

    In this paper, we study the free boundary problem for 1D compressible Navier-Stokes equations with density-dependent viscosity. We focus on the case where the viscosity coefficient vanishes on vacuum. We prove the global existence and uniqueness for discontinuous solutions to the Navier-Stokes equations when the initial density is a bounded variation function, and give a decay result for the density as t-->+[infinity].

  14. Ammonia inhibition on Arthrospira platensis in relation to the initial biomass density and pH.

    PubMed

    Markou, Giorgos; Vandamme, Dries; Muylaert, Koenraad

    2014-08-01

    In this study the combined effect of total ammoniacal nitrogen (TAN) concentration, initial biomass density and initial pH of the cultivation medium on growth of Arthrospira platensis was studied. The results indicate that TAN inhibition in relation to the initial biomass in unregulated pH cultures is neither a clearly biomass-independent nor biomass-dependent phenomenon. However, low biomass densities are more susceptible to ammonia inhibition than higher biomass densities. Higher biomass densities seems to mitigate ammonia inhibition through rapider assimilation of TAN. In all cases studied the growth rates were lower compared to the cultures with nitrate as nitrogen source. It was observed that at low TAN concentration, although no ammonia inhibition occured the growth rates were decreased due to nitrogen limitation. Low TAN concentration triggered the accumulation of carbohydrates affecting thus significantly the biomass composition. Ammonia losses from the cultivation system were also determined. Ammonia losses ranged between 17% and 80%.

  15. Heterogeneous growth fingerlings of the Nile tilapia Oreochromis niloticus: effects of density and initial size variability.

    PubMed

    Barbosa, J M; Brugiolo, S S S; Carolsfeld, J; Leitão, S S

    2006-05-01

    In this study, the effect of initial heterogeneity of weight and density on heterogeneous growth (HetG) evaluated by the coefficient of the variation of weight in the young Nile tilapia Oreochromis niloticus of the territorial species was tested. Fish were maintained in a glass aquarium (8 and 2 L of water) with two levels of initial heterogeneity of weight: low and high, under two density conditions: low and high, thus constituting four conditions (six replications for each). Initially, the weights of the animals were taken after 8, 16, 22 and 30 days (end of experiment). The results, evaluated by the non-parametric test of Kruskal- Wallis, demonstrated that in the groups where the animals were stored under high initial HetG, there was a reduction of the same and that in the groups where the animals were stored under high density, there was exacerbation or maintained high values of HetG. High density in association with high initial heterogeneity caused more exacerbation of HetG in such a way that the density appeared to be a determining factor for exacerbation or the maintenance of high values of HetG, whereas the initial heterogeneity of the weight could be a secondary factor.

  16. Fabrication of pillared PLGA microvessel scaffold using femtosecond laser ablation

    PubMed Central

    Wang, Hsiao-Wei; Cheng, Chung-Wei; Li, Ching-Wen; Chang, Han-Wei; Wu, Ping-Han; Wang, Gou-Jen

    2012-01-01

    One of the persistent challenges confronting tissue engineering is the lack of intrinsic microvessels for the transportation of nutrients and metabolites. An artificial microvascular system could be a feasible solution to this problem. In this study, the femtosecond laser ablation technique was implemented for the fabrication of pillared microvessel scaffolds of polylactic-co-glycolic acid (PLGA). This novel scaffold facilitates implementation of the conventional cell seeding process. The progress of cell growth can be observed in vitro by optical microscopy. The problems of becoming milky or completely opaque with the conventional PLGA scaffold after cell seeding can be resolved. In this study, PLGA microvessel scaffolds consisting of 47 μm × 80 μm pillared branches were produced. Results of cell culturing of bovine endothelial cells demonstrate that the cells adhere well and grow to surround each branch of the proposed pillared microvessel networks. PMID:22605935

  17. Structure-based algorithms for microvessel classification.

    PubMed

    Smith, Amy F; Secomb, Timothy W; Pries, Axel R; Smith, Nicolas P; Shipley, Rebecca J

    2015-02-01

    Recent developments in high-resolution imaging techniques have enabled digital reconstruction of three-dimensional sections of microvascular networks down to the capillary scale. To better interpret these large data sets, our goal is to distinguish branching trees of arterioles and venules from capillaries. Two novel algorithms are presented for classifying vessels in microvascular anatomical data sets without requiring flow information. The algorithms are compared with a classification based on observed flow directions (considered the gold standard), and with an existing resistance-based method that relies only on structural data. The first algorithm, developed for networks with one arteriolar and one venular tree, performs well in identifying arterioles and venules and is robust to parameter changes, but incorrectly labels a significant number of capillaries as arterioles or venules. The second algorithm, developed for networks with multiple inlets and outlets, correctly identifies more arterioles and venules, but is more sensitive to parameter changes. The algorithms presented here can be used to classify microvessels in large microvascular data sets lacking flow information. This provides a basis for analyzing the distinct geometrical properties and modelling the functional behavior of arterioles, capillaries, and venules. © 2014 The Authors. Microcirculation published by John Wiley & Sons Ltd.

  18. [Effect of initial population density on resting egg formation of rotifer Brachionus calyciflorus].

    PubMed

    Xi, Y; Huang, X

    2000-04-01

    With the method of population accumulative culture, the effect of initial population density on the formation of resting eggs of freshwater rotifer(Brachionus calyciflorus), and on the rates of mictic female and fertilization was studied. During 11 days culture, the productivity and the formation efficiency of resting eggs, and the mean rate of mictic female were the biggest when the initial population density was 1.0-10.0 ind.ml-1, second by the density of 20.0 ind.ml-1, and the lowest by the density of 50.0 ind.ml-1. There was no significant effect of initial population density on the fertilization rate. Statistical analysis on maximum formation efficiency of resting eggs, their emergence and productivity showed that when the production of resting eggs was large-scaled proceeded, the feasible initial population density should be 10.0 ind.ml-1, and the corresponding time should be 6 days to obtain a higher yield of resting eggs and a higher formation efficiency.

  19. Physiological responses to acid stress by Saccharomyces cerevisiae when applying high initial cell density

    PubMed Central

    Guo, Zhong-peng; Olsson, Lisbeth

    2016-01-01

    High initial cell density is used to increase volumetric productivity and shorten production time in lignocellulosic hydrolysate fermentation. Comparison of physiological parameters in high initial cell density cultivation of Saccharomyces cerevisiae in the presence of acetic, formic, levulinic and cinnamic acids demonstrated general and acid-specific responses of cells. All the acids studied impaired growth and inhibited glycolytic flux, and caused oxidative stress and accumulation of trehalose. However, trehalose may play a role other than protecting yeast cells from acid-induced oxidative stress. Unlike the other acids, cinnamic acid did not cause depletion of cellular ATP, but abolished the growth of yeast on ethanol. Compared with low initial cell density, increasing initial cell density reduced the lag phase and improved the bioconversion yield of cinnamic acid during acid adaptation. In addition, yeast cells were able to grow at elevated concentrations of acid, probable due to the increase in phenotypic cell-to-cell heterogeneity in large inoculum size. Furthermore, the specific growth rate and the specific rates of glucose consumption and metabolite production were significantly lower than at low initial cell density, which was a result of the accumulation of a large fraction of cells that persisted in a viable but non-proliferating state. PMID:27620460

  20. Physiological responses to acid stress by Saccharomyces cerevisiae when applying high initial cell density.

    PubMed

    Guo, Zhong-Peng; Olsson, Lisbeth

    2016-11-01

    High initial cell density is used to increase volumetric productivity and shorten production time in lignocellulosic hydrolysate fermentation. Comparison of physiological parameters in high initial cell density cultivation of Saccharomyces cerevisiae in the presence of acetic, formic, levulinic and cinnamic acids demonstrated general and acid-specific responses of cells. All the acids studied impaired growth and inhibited glycolytic flux, and caused oxidative stress and accumulation of trehalose. However, trehalose may play a role other than protecting yeast cells from acid-induced oxidative stress. Unlike the other acids, cinnamic acid did not cause depletion of cellular ATP, but abolished the growth of yeast on ethanol. Compared with low initial cell density, increasing initial cell density reduced the lag phase and improved the bioconversion yield of cinnamic acid during acid adaptation. In addition, yeast cells were able to grow at elevated concentrations of acid, probable due to the increase in phenotypic cell-to-cell heterogeneity in large inoculum size. Furthermore, the specific growth rate and the specific rates of glucose consumption and metabolite production were significantly lower than at low initial cell density, which was a result of the accumulation of a large fraction of cells that persisted in a viable but non-proliferating state. © FEMS 2016.

  1. Astroglia-microvessel relationship in the developing human telencephalon.

    PubMed

    Virgintino, D; Maiorano, E; Errede, M; Vimercati, A; Greco, P; Selvaggi, L; Roncali, L; Bertossi, M

    1998-11-01

    The telencephalon of 12 and 18 week-old human foetuses was examined for evidence of astroglia-microvessel relationship. Immature astroglia cells (radial glia and astroblasts) and astrocytes were immunostained using antibodies to the cytoskeletal proteins vimentin (VIM) and glial fibrillary acidic protein (GFAP). The microvessels were detected using an antibody to the blood-brain barrier (BBB)-specific glucose transporter GLUT1. Two extracellular matrix (ECM) glycoproteins, laminin (LM), an endothelial-derived molecule, and tenascin-C (TN-C), a glia-derived molecule, were also analyzed. In the two stages examined, VIM- and GFAP-positive fibers of the radial glia establish close relationships with the radial and periventricular microvessels, which are GLUT1-positive and lined by an LM-positive basal lamina-like matrix. At the 18th week, also radial glia transitional forms and immature astrocytes exhibit extensive contacts with the microvasculature. A TN-C-rich ECM is revealed around the vascular plexus of ventricular zones at the 12th week, and around the newly growing radial microvessels and the microvessel branching sites at the 18th week. The observations taken as a whole, suggest that during the telencephalon morphogenesis the immature astroglia cells play a role in the early establishment of the distribution pattern of the neural microvessels and in their growth and maturation.

  2. Effect of osmolarity on potassium transport in isolated cerebral microvessels

    SciTech Connect

    Lin, J.D.

    1988-01-01

    Potassium transport in microvessels isolated from rat brain by a technique involving density gradient centrifugation was studied in HEPES buffer solutions of varying osmolarity from 200 to 420 mosmols, containing different concentration of sodium chloride, choline chloride, or sodium nitrate. The flux of /sup 86/Rb into and out of the endothelial cells was estimated. Potassium influx was very sensitive to the osmolarity of the medium. Ouabain-insensitive K-component was reduced in hypotonic medium and was increased in medium made hypertonic with sodium chloride or mannitol. Choline chloride replacement caused a large reduction in K influx. Potassium influx was significant decrease when nitrate is substituted for chloride ion in isotonic and hypertonic media, whereas a slight decrease was found in hypotonic medium. The decrease of K influx in the ion-replacement medium is due to a decrement of the ouabain-insensitive component. Potassium efflux was unchanged in hypotonic medium but was somewhat reduced in hypertonic medium. The marked effect of medium osmolarity of K fluxes suggests that these fluxes may be responsible for the volume regulatory K movements. The possible mechanism of changes of K flux under anisotonic media is also discussed.

  3. Shock initiation experiments with ignition and growth modeling on low density HMX

    NASA Astrophysics Data System (ADS)

    Garcia, Frank; Vandersall, Kevin S.; Tarver, Craig M.

    2014-05-01

    Shock initiation experiments on low density (~1.2 and ~1.6 g/cm3) HMX were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (~1.2 g/cm3) or sample disks pressed to low density (~1.6 g/cm3). The measured shock sensitivity of the ~1.2 g/cm3 HMX was similar to that previously measured by Sheffield et al. and the ~1.6 g/cm3 HMX was measured to be much less shock sensitive. Ignition and Growth model parameters were utilized that yielded good agreement with the experimental data at both initial densities.

  4. On the thermodynamic origin of the initial radiation energy density in warm inflation

    NASA Astrophysics Data System (ADS)

    Gim, Yongwan; Kim, Wontae

    2016-11-01

    In warm inflation scenarios, radiation always exists, so that the radiation energy density is also assumed to be finite when inflation starts. To find out the origin of the non-vanishing initial radiation energy density, we revisit thermodynamic analysis for a warm inflation model and then derive an effective Stefan-Boltzmann law which is commensurate with the temperature-dependent effective potential by taking into account the non-vanishing trace of the total energy-momentum tensors. The effective Stefan-Boltzmann law shows that the zero energy density for radiation at the Grand Unification epoch increases until the inflation starts and it becomes eventually finite at the initial stage of warm inflation. By using the above effective Stefan-Boltzmann law, we also study the cosmological scalar perturbation, and obtain the sufficient radiation energy density in order for GUT baryogenesis at the end of inflation.

  5. Erythrocyte hemodynamics in stenotic microvessels: A numerical investigation

    NASA Astrophysics Data System (ADS)

    Wang, T.; Xing, Z. W.

    2013-10-01

    This paper presents a two-dimensional numerical investigation of deformation and motion of erythrocytes in stenotic microvessels using the immersed boundary-fictitious domain method. The erythrocytes were modeled as biconcave-shaped closed membranes filled with cytoplasm. We studied the biophysical characteristics of human erythrocytes traversing constricted microchannels with the narrowest cross-sectional diameter as small as 3 μm. The effects of essential parameters, namely, stenosis severity, shape of the erythrocytes, and erythrocyte membrane stiffness, were simulated and analyzed in this study. Moreover, simulations were performed to discuss conditions associated with the shape transitions of the cells along with the relative effects of radial position and initial orientation of erythrocytes, membrane stiffness, and plasma environments. The simulation results were compared with existing experiment findings whenever possible, and the physical insights obtained were discussed. The proposed model successfully simulated rheological behaviors of erythrocytes in microscale flow and thus is applicable to a large class of problems involving fluid flow with complex geometry and fluid-cell interactions. Our study would be helpful for further understanding of pathology of malaria and some other blood disorders.

  6. Erythrocyte hemodynamics in stenotic microvessels: A numerical investigation

    NASA Astrophysics Data System (ADS)

    Wang, Tong; Xing, Zhongwen

    2014-03-01

    This paper presents a two-dimensional numerical investigation of deformation and motion of erythrocytes in stenotic microvessels using the immersed boundary-fictitious domain method. The erythrocytes were modeled as biconcave-shaped closed membranes filled with cytoplasm. We studied the biophysical characteristics of human erythrocytes traversing constricted microchannels with the narrowest cross-sectional diameter as small as 3 μm. The effects of essential parameters, namely, stenosis severity, shape of the erythrocytes, and erythrocyte membrane stiffness, were simulated and analyzed in this study. Moreover, simulations were performed to discuss conditions associated with the shape transitions of the cells along with the relative effects of radial position and initial orientation of erythrocytes, membrane stiffness, and plasma environments. The simulation results were compared with existing experiment findings whenever possible, and the physical insights obtained were discussed. The proposed model successfully simulated rheological behaviors of erythrocytes in microscale flow and thus is applicable to a large class of problems involving fluid flow with complex geometry and fluid-cell interactions. Our study would be helpful for further understanding of pathology of malaria and some other blood disorders.

  7. Erythrocyte hemodynamics in stenotic microvessels: a numerical investigation.

    PubMed

    Wang, T; Xing, Z W

    2013-10-01

    This paper presents a two-dimensional numerical investigation of deformation and motion of erythrocytes in stenotic microvessels using the immersed boundary-fictitious domain method. The erythrocytes were modeled as biconcave-shaped closed membranes filled with cytoplasm. We studied the biophysical characteristics of human erythrocytes traversing constricted microchannels with the narrowest cross-sectional diameter as small as 3 μm. The effects of essential parameters, namely, stenosis severity, shape of the erythrocytes, and erythrocyte membrane stiffness, were simulated and analyzed in this study. Moreover, simulations were performed to discuss conditions associated with the shape transitions of the cells along with the relative effects of radial position and initial orientation of erythrocytes, membrane stiffness, and plasma environments. The simulation results were compared with existing experiment findings whenever possible, and the physical insights obtained were discussed. The proposed model successfully simulated rheological behaviors of erythrocytes in microscale flow and thus is applicable to a large class of problems involving fluid flow with complex geometry and fluid-cell interactions. Our study would be helpful for further understanding of pathology of malaria and some other blood disorders.

  8. Shock Initiation Experiments with Ignition and Growth Modeling on Low Density Composition B

    NASA Astrophysics Data System (ADS)

    Vandersall, Kevin S.; Garcia, Frank; Tarver, Craig M.

    2015-06-01

    Shock initiation experiments on low density (~1.2 and ~1.5 g/cm3) Composition B were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (~1.2 g/cm3) confined in Teflon rings or sample disks pressed to low density (~1.5 g/cm3) . The shock sensitivity was found to increase with decreasing density as expected. Ignition and Growth model parameters were derived that yielded reasonable agreement with the experimental data at both initial densities. The shock sensitivity at the tested densities will be compared to prior work published as near full density material. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. This work was funded in part by the Joint DoD-DOE Munitions Program.

  9. Rapidity profile of the initial energy density in heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Özönder, Şener; Fries, Rainer J.

    2014-03-01

    The rapidity dependence of the initial energy density in heavy-ion collisions is calculated from a three-dimensional McLerran-Venugopalan model introduced by Lam and Mahlon. This model is infrared safe since global color neutrality is enforced. In this framework, the nuclei have nonzero thickness in the longitudinal direction. This leads to Bjorken-x-dependent unintegrated gluon distribution functions, which in turn result in a rapidity-dependent initial energy density after the collision. These unintegrated distribution functions are substituted in the initial energy density expression, which has been derived for the boost-invariant case. We argue that using three-dimensional (x-dependent) unintegrated distribution functions together with the boost-invariant energy formula is consistent given that the overlap of the two nuclei lasts less than the natural time scale for the evolution of the fields (1/Qs) after the collision. The initial energy density and its rapidity dependence are important initial conditions for the quark gluon plasma and its hydrodynamic evolution.

  10. On the logistic equation subject to uncertainties in the environmental carrying capacity and initial population density

    NASA Astrophysics Data System (ADS)

    Dorini, F. A.; Cecconello, M. S.; Dorini, L. B.

    2016-04-01

    It is recognized that handling uncertainty is essential to obtain more reliable results in modeling and computer simulation. This paper aims to discuss the logistic equation subject to uncertainties in two parameters: the environmental carrying capacity, K, and the initial population density, N0. We first provide the closed-form results for the first probability density function of time-population density, N(t), and its inflection point, t*. We then use the Maximum Entropy Principle to determine both K and N0 density functions, treating such parameters as independent random variables and considering fluctuations of their values for a situation that commonly occurs in practice. Finally, closed-form results for the density functions and statistical moments of N(t), for a fixed t > 0, and of t* are provided, considering the uniform distribution case. We carried out numerical experiments to validate the theoretical results and compared them against that obtained using Monte Carlo simulation.

  11. In Silico Investigation of Angiogenesis with Growth and Stress Generation Coupled to Local Extracellular Matrix Density

    PubMed Central

    Edgar, Lowell T.; Hoying, James B.; Weiss, Jeffrey A.

    2015-01-01

    Mechanical interactions during angiogenesis, i.e., traction applied by neovessels to the extracellular matrix and the corresponding deformation, are important regulators of growth and neovascularization. We have previously designed, implemented, and validated a coupled model of angiogenesis in which a discrete microvessel growth model interacts with a continuous finite element mesh through the application of local remodeling sprout stresses (Edgar et al. in Biomech Model Mechanobiol, 2014). However, the initial implementation of this framework does not take matrix density into account when determined these remodeling stresses and is therefore insufficient for the study of angiogenesis within heterogeneous matrix environments such as those found in vivo. The objective of this study was to implement sensitivity to matrix density in the active stress generation within AngioFE in order to allow the study of angiogenic growth within a heterogeneous density environment. We accomplished this by scaling active sprout stresses relative to local matrix density using a scaling factor previously determined from experimental data. We then exercised the new functionality of the model by simulating angiogenesis within four different scenarios: homogeneous density, a narrow gap model, and matrix density gradient, and a construct subjected to repeated loading/unloading and preconditioning. These numerical experiments predicted heterogeneous matrix density in the initially homogeneous case, the closure and alignment of microvessels along a low-density gap, the formation of a unique cap-like structure during angiogenesis within a density gradient, and the alignment of microvessels in the absence of applied load due to preconditioning. The result of these in silico investigations demonstrate how matrix heterogeneity affects neovascularization and matrix deformation and provides a platform for studying angiogenesis in complicated and multi-faceted mechanical environments that

  12. Centrizonal Arteries and Microvessels in Non-Alcoholic Steatohepatitis

    PubMed Central

    Gill, Ryan M.; Belt, Patricia; Wilson, Laura; Bass, Nathan M.; Ferrell, Linda D.

    2011-01-01

    Correct classification of non-alcoholic steatohepatitis (NASH) liver biopsies is of critical importance and relies on correct orientation to microscopic liver architecture. Centrizonal arteries can cause central zones to be mistaken for portal tracts, especially in the setting of centrizonal ductular reaction, and result in either missed diagnosis or inaccurate staging of NASH. 100 randomly selected biopsies from NASH Clinical Research Network participants (2/05-8/06, fibrosis stage >1a,) were evaluated for arteries and CD34 positive microvessels in the centrizonal region. Prevalence of both centrizonal arteries and CD34 positive microvessels was graded as 0 (none in central zones), 1 (1-2 central zones with vessels), 2 (< 50% of central zones with vessels), or 3 (≥ 50% of central zones with vessels). Centrizonal arteries and CD34 positive microvessels were present in 40 and 100 cases (40% and 100%), respectively. Arteries and CD34 positive microvessels were more commonly found in central zones in biopsies with greater degrees of fibrosis; 62% with arteries in stage 3-4 vs. 21% in stage 1-2 and 70% with microvessels in stage 3-4 vs. 25% in stage 1-2, with increased prevalence of both centrizonal arteries and CD34 positive microvessels correlating directly with fibrosis stage (p<0.001). Ductular reaction was a common finding (55%) in patients with central zone arteries. The presence of an aberrant centrizonal artery must be recognized to allow for correct orientation to liver architecture in NASH and, together with the finding of increased CD34 positive microvessel formation in higher stage fibrosis, suggests a possible association between neoangiogenesis and NASH progression to cirrhosis. PMID:21836480

  13. Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels

    PubMed Central

    Tsai, Philbert S.; Kaufhold, John P.; Blinder, Pablo; Friedman, Beth; Drew, Patrick J.; Karten, Harvey J.; Lyden, Patrick D.; Kleinfeld, David

    2016-01-01

    It is well known that the density of neurons varies within the adult brain. In neocortex, this includes variations in neuronal density between different lamina as well as between different regions. Yet the concomitant variation of the microvessels is largely uncharted. Here we present automated histological, imaging, and analysis tools to simultaneously map the locations of all neuronal and non-neuronal nuclei and the centerlines and diameters of all blood vessels within thick slabs of neocortex from mice. Based on total inventory measurements of different cortical regions (~ 107 cells vectorized across brains), these methods revealed: (1) In three dimensions, the mean distance of the center of neuronal somata to the closest microvessel was 14 μm. (2) Volume samples within lamina of a given region show that the density of microvessels does not match the strong laminar variation in neuronal density. This holds for both agranular and granular cortex. (3) Volume samples in successive radii from the midline to the ventral-lateral edge, where each volume summed the number of cells and microvessels from the pia to the white matter, show a significant correlation between neuronal and microvessel densities. These data show that while neuronal and vascular densities do not track each other on the 100 μm scale of cortical lamina, they do track each other on the 1 – 10 mm scale of the cortical mantle. The absence of a disproportionate density of blood vessels in granular lamina is argued to be consistent with the initial locus of functional brain imaging signals. PMID:19923289

  14. LABORATORY CULTURE OF CHIRONOMUS TENTANS FOR USE IN TOXICITY TESTING: OPTIMUM INITIAL EGG STOCKING DENSITIES

    EPA Science Inventory

    This study was conducted to determine the effet of initial culture stocking density on: (1) post-hatch (larval) dry weight, body length and head-capsule width at 10 and 20 days; (2) time to emergence; (3) number and sex of emergent adults; (4) number of larvae and pupae at test t...

  15. LABORATORY CULTURE OF CHIRONOMUS TENTANS FOR USE IN TOXICITY TESTING: OPTIMUM INITIAL EGG STOCKING DENSITIES

    EPA Science Inventory

    This study was conducted to determine the effet of initial culture stocking density on: (1) post-hatch (larval) dry weight, body length and head-capsule width at 10 and 20 days; (2) time to emergence; (3) number and sex of emergent adults; (4) number of larvae and pupae at test t...

  16. Tortuous Microvessels Contribute to Wound Healing via Sprouting Angiogenesis.

    PubMed

    Chong, Diana C; Yu, Zhixian; Brighton, Hailey E; Bear, James E; Bautch, Victoria L

    2017-10-01

    Wound healing is accompanied by neoangiogenesis, and new vessels are thought to originate primarily from the microcirculation; however, how these vessels form and resolve during wound healing is poorly understood. Here, we investigated properties of the smallest capillaries during wound healing to determine their spatial organization and the kinetics of formation and resolution. We used intravital imaging and high-resolution microscopy to identify a new type of vessel in wounds, called tortuous microvessels. Longitudinal studies showed that tortuous microvessels increased in frequency after injury, normalized as the wound healed, and were closely associated with the wound site. Tortuous microvessels had aberrant cell shapes, increased permeability, and distinct interactions with circulating microspheres, suggesting altered flow dynamics. Moreover, tortuous microvessels disproportionately contributed to wound angiogenesis by sprouting exuberantly and significantly more frequently than nearby normal capillaries. A new type of transient wound vessel, tortuous microvessels, sprout dynamically and disproportionately contribute to wound-healing neoangiogenesis, likely as a result of altered properties downstream of flow disturbances. These new findings suggest entry points for therapeutic intervention. © 2017 The Authors.

  17. Cold dissipationless collapse of spherical systems - Sensitivity to the initial density law

    NASA Technical Reports Server (NTRS)

    Cannizzo, John K.; Hollister, Timothy C.

    1992-01-01

    The collapse of cold, initially spherical systems with varying degrees of central condensation is investigated. The way in which the final shape of a collapsing system depends on the initial density law is examined. For an initial stellar number density rho varies as r exp -n, where n is in the range 0-2.5, the final, nearly prolate shape is given by a/c is approximately equal to 1.28(1 + 0.16 n), where a/c is the ratio of long to short axes of the inertia ellipsoid computed from the moment of inertia tensor of the most tightly bound 80 percent of the mass. The properties associated with the final states in the present computations are also studied. The collapsing systems develop an anisotropic halo dominated by radial orbits surrounding an isotropic core as predicted by Burkert (1990).

  18. Determination of an Initial Mesh Density for Finite Element Computations via Data Mining

    SciTech Connect

    Kanapady, R; Bathina, S K; Tamma, K K; Kamath, C; Kumar, V

    2001-07-23

    Numerical analysis software packages which employ a coarse first mesh or an inadequate initial mesh need to undergo a cumbersome and time consuming mesh refinement studies to obtain solutions with acceptable accuracy. Hence, it is critical for numerical methods such as finite element analysis to be able to determine a good initial mesh density for the subsequent finite element computations or as an input to a subsequent adaptive mesh generator. This paper explores the use of data mining techniques for obtaining an initial approximate finite element density that avoids significant trial and error to start finite element computations. As an illustration of proof of concept, a square plate which is simply supported at its edges and is subjected to a concentrated load is employed for the test case. Although simplistic, the present study provides insight into addressing the above considerations.

  19. Effects of wall shear stress and its gradient on tumor cell adhesion in curved microvessels

    PubMed Central

    Yan, W. W.; Cai, B.

    2016-01-01

    Tumor cell adhesion to vessel walls in the microcirculation is one critical step in cancer metastasis. In this paper, the hypothesis that tumor cells prefer to adhere at the microvessels with localized shear stresses and their gradients, such as in the curved microvessels, was examined both experimentally and computationally. Our in vivo experiments were performed on the microvessels (post-capillary venules, 30–50 μm diameter) of rat mesentery. A straight or curved microvessel was cannulated and perfused with tumor cells by a glass micropipette at a velocity of ~1mm/s. At less than 10 min after perfusion, there was a significant difference in cell adhesion to the straight and curved vessel walls. In 60 min, the averaged adhesion rate in the curved vessels (n = 14) was ~1.5-fold of that in the straight vessels (n = 19). In 51 curved segments, 45% of cell adhesion was initiated at the inner side, 25% at outer side, and 30% at both sides of the curved vessels. To investigate the mechanical mechanism by which tumor cells prefer adhering at curved sites, we performed a computational study, in which the fluid dynamics was carried out by the lattice Boltzmann method, and the tumor cell dynamics was governed by the Newton’s law of translation and rotation. A modified adhesive dynamics model that included the influence of wall shear stress/gradient on the association/dissociation rates of tumor celladhesion was proposed, in which the positive wall shear stress/gradient jump would enhance tumor cell adhesion while the negative wall shear stress/gradient jump would weaken tumor cell adhesion. It was found that the wall shear stress/gradient, over a threshold, had significant contribution to tumor cell adhesion by activating or inactivating cell adhesion molecules. Our results elucidated why the tumor cell adhesion prefers to occur at the positive curvature of curved microvessels with very low Reynolds number (in the order of 10−2) laminar flow. PMID:21818636

  20. Association between Dietary Energy Density and Incident Type 2 Diabetes in the Women's Health Initiative.

    PubMed

    Hingle, Melanie D; Wertheim, Betsy C; Neuhouser, Marian L; Tinker, Lesley F; Howard, Barbara V; Johnson, Karen; Liu, Simin; Phillips, Lawrence S; Qi, Lihong; Sarto, Gloria; Turner, Tami; Waring, Molly E; Thomson, Cynthia A

    2017-05-01

    Dietary energy density, or energy available in relation to gram intake, can inform disease risk. The objective of this study was to investigate the association between baseline dietary energy density and risk of incident type 2 diabetes in postmenopausal women. Dietary energy density, weight status, and type 2 diabetes incidence were prospectively characterized in a large cohort of postmenopausal women participating in one or more clinical trials or an observational study. The study involved 161,808 postmenopausal women recruited to the Women's Health Initiative observational study or clinical trials at 40 centers across the United States between 1993 and 1998. The primary outcome was incident type 2 diabetes. The association between dietary energy density quintiles and incident diabetes was tested using Cox proportional hazards regression. A total of 143,204 participants without self-reported diabetes at enrollment completed baseline dietary assessment and were followed for 12.7±4.6 years. Risk of diabetes developing was 24% greater for women in the highest dietary energy density quintile compared with the lowest after adjusting for confounders (95% CI 1.17 to 1.32). Body mass index (calculated as kg/m(2)) and waist circumference mediated the relationship between dietary energy density and diabetes. In waist circumference-stratified analysis, women in dietary energy density quintiles 2 to 5 with waist circumferences >88 cm were at 9% to 12% greater risk of diabetes developing compared with women with waist circumference ≤88 cm. In this prospective study, a higher baseline dietary energy density was associated with higher incidence of type 2 diabetes among postmenopausal women, both overall, and in women with elevated waist circumference. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  1. Shock Initiation Experiments with Ignition and Growth Modeling on Low Density HMX

    NASA Astrophysics Data System (ADS)

    Garcia, Frank; Vandersall, Kevin; Tarver, Craig

    2013-06-01

    Shock initiation experiments on low density (1.24 and 1.64 g/cm3) HMX were performed to obtain in-situ pressure gauge data, characterize the run-distance-to-detonation behavior, and provide a basis for Ignition and Growth reactive flow modeling. A 101 mm diameter gas gun was utilized to initiate the explosive charges with manganin piezoresistive pressure gauge packages placed between packed layers (1.24 g/cm3) or sample disks pressed to low density (1.64 g/cm3) . The measured shock sensitivity of the 1.24 g/cm3 HMX was similar to that previously measured by Dick and Sheffield et al. and the 1.64 g/cm3 HMX was measured to be much less shock sensitive. Ignition and Growth model parameters were derived that yielded good agreement with the experimental data at both initial densities. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  2. Loading of atoms into an optical trap with high initial phase-space density

    NASA Astrophysics Data System (ADS)

    Shibata, Kosuke; Yonekawa, Shota; Tojo, Satoshi

    2017-07-01

    We report a method for loading cold atoms into an optical trap with high initial phase-space density (PSD). When the trap beam is overlapped with atoms in optical molasses of optimized parameters including large cooling beam detuning compared with conventional detuning used for a magneto-optical trap (MOT), more than 3 ×106 rubidium atoms with an initial temperature less than 20 μ K are loaded into a single beam trap. The obtained maximum initial PSD is estimated to be 1.1 ×10-3 , which is one or two orders of magnitude greater than that achieved with the conventional loading into an optical trap from atoms in a MOT. The proposed method is promising for creating a quantum gas with a large number of atoms in a short evaporation time.

  3. Imaging of lymph flow in single microvessels in vivo

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekateryna I.; Ulyanov, Sergey S.; Tuchin, Valery V.; Brill, Gregory E.; Solov'eva, Anastasiya V.

    2000-10-01

    In this study parameters of lymph microcirculation are investigated. The microcirculation was studied on small intestine mesentery in norm and during Dimethyl sulfoxide (DMSO) application. The direct measurement of lymph flow velocity (parameter V) in individual microvessels was based on the technique of light intravital videomicroscopy. The first spectral moments of Doppler signal, characterizing the mean velocities of lymph flow in microvessels (parameter M1), were measured by speckle-interferometrical method. Simultaneously, diameters of lymph microvessels as well as parameters of phasic contractions and valve function of lymphatics were registered. The value of V was very changeable; the mean V was equal to 270+/- 24micrometers /s. The M1 was the varying characteristic of the lymph flow too. The temporal dynamic of M1 was reflected alternating- translation motion of lymph flow. DMSO application during 15 min caused the constriction in a majority of lymphatics and the phasic contractions. DMSO induced lymphostatis in 20% of cases. But the other microvessels responded to the rise of lymph flow velocity. These changes led to the stimulation of drainage function of lymph microcirculation function.

  4. Mechanical behavior of the erythrocyte in microvessel stenosis.

    PubMed

    Zhang, ZhiGuo; Zhang, XiWen

    2011-05-01

    The passage of red blood cells (RBCs) through capillaries is essential for human blood microcirculation. This study used a moving mesh technology that incorporated leader-follower pairs to simulate the fluid-structure and structure-structure interactions between the RBC and a microvessel stenosis. The numerical model consisted of plasma, cytoplasm, the erythrocyte membrane, and the microvessel stenosis. Computational results showed that the rheology of the RBC is affected by the Reynolds number of the plasma flow as well as the surface-to-volume ratio of the erythrocyte. At a constant inlet flow rate, an increased plasma viscosity will improve the transit of the RBC through the microvessel stenosis. For the above reasons, we consider that the decreased hemorheology in microvessels in a pathological state may primarily be attributed to an increase in the number of white blood cells. This leads to the aggregation of RBCs and a change in the blood flow structure. The present fundamental study of hemorheology aimed at providing theoretical guidelines for clinical hemorheology.

  5. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  6. Fluids density functional theory and initializing molecular dynamics simulations of block copolymers

    NASA Astrophysics Data System (ADS)

    Brown, Jonathan R.; Seo, Youngmi; Maula, Tiara Ann D.; Hall, Lisa M.

    2016-03-01

    Classical, fluids density functional theory (fDFT), which can predict the equilibrium density profiles of polymeric systems, and coarse-grained molecular dynamics (MD) simulations, which are often used to show both structure and dynamics of soft materials, can be implemented using very similar bead-based polymer models. We aim to use fDFT and MD in tandem to examine the same system from these two points of view and take advantage of the different features of each methodology. Additionally, the density profiles resulting from fDFT calculations can be used to initialize the MD simulations in a close to equilibrated structure, speeding up the simulations. Here, we show how this method can be applied to study microphase separated states of both typical diblock and tapered diblock copolymers in which there is a region with a gradient in composition placed between the pure blocks. Both methods, applied at constant pressure, predict a decrease in total density as segregation strength or the length of the tapered region is increased. The predictions for the density profiles from fDFT and MD are similar across materials with a wide range of interfacial widths.

  7. Fluids density functional theory and initializing molecular dynamics simulations of block copolymers.

    PubMed

    Brown, Jonathan R; Seo, Youngmi; Maula, Tiara Ann D; Hall, Lisa M

    2016-03-28

    Classical, fluids density functional theory (fDFT), which can predict the equilibrium density profiles of polymeric systems, and coarse-grained molecular dynamics (MD) simulations, which are often used to show both structure and dynamics of soft materials, can be implemented using very similar bead-based polymer models. We aim to use fDFT and MD in tandem to examine the same system from these two points of view and take advantage of the different features of each methodology. Additionally, the density profiles resulting from fDFT calculations can be used to initialize the MD simulations in a close to equilibrated structure, speeding up the simulations. Here, we show how this method can be applied to study microphase separated states of both typical diblock and tapered diblock copolymers in which there is a region with a gradient in composition placed between the pure blocks. Both methods, applied at constant pressure, predict a decrease in total density as segregation strength or the length of the tapered region is increased. The predictions for the density profiles from fDFT and MD are similar across materials with a wide range of interfacial widths.

  8. Fingerprints of the initial conditions on the density profiles of cold and warm dark matter haloes

    NASA Astrophysics Data System (ADS)

    Polisensky, E.; Ricotti, M.

    2015-06-01

    We use N-body simulations of dark matter haloes in cold dark matter (CDM) and a large set of different warm dark matter (WDM) cosmologies to demonstrate that the spherically averaged density profile of dark matter haloes has a shape that depends on the power spectrum of matter perturbations. Density profiles are steeper in WDM but become shallower at r < 0.01Rvir. Virialization isotropizes the velocity dispersion in the inner regions of the halo but does not erase the memory of the initial conditions in phase space. The location of the observed deviations from CDM in the density profile and in phase space can be directly related to the ratio between the halo mass and the filtering mass and are most evident in small mass haloes, even for a 34 keV thermal relic WDM. The rearrangement of mass within the haloes supports analytic models of halo structure that include angular momentum. We also find evidence of a dependence of the slope of the inner density profile in CDM cosmologies on the halo mass with more massive haloes exhibiting steeper profiles, in agreement with the model predictions and with previous simulation results. Our work complements recent studies of microhaloes near the filtering scale in CDM and strongly argue against a universal shape for the density profile.

  9. Effect of initiator concentration to low-density polyethylene production in a tubular reactor

    NASA Astrophysics Data System (ADS)

    Azmi, A.; Aziz, N.

    2016-11-01

    Low-density polyethylene (LDPE) is one of the most widely used polymers in the world, which is produced in high-capacity tubular and autoclave reactors. As the LDPE industry turn into more competitive and its market profit margins become tighter, manufacturers have to develop solutions to debottleneck the reactor output while abiding to the stringent product specification. A single polyolefin plant producing ten to forty grades of LDPE with various melt flow index (MFI), therefore understanding the reaction mechanism, the operating conditions as well as the dynamic behavior of tubular reactor is essential before any improvement can take place. In the present work, a steady state mathematical model representing a tubular reactor for the production of LDPE is simulated using MATLAB R2015a®. The model developed is a function of feed inlet, reactor jacket, single initiator injector and outlet stream. Analysis on the effect of initiator concentration (CI) shows sudden declining trend of initiator's concentration which indicates that all of the initiators are exhausted after polymerization reaction and no further reaction occur from this point onwards. Furthermore, the results demonstrate that the concentration of initiator gives significant impact on reactor temperature's profile and monomer conversion rate, since higher initiator concentration promotes greater polymerization rate, and therefore leads to higher monomer conversion throughput.

  10. Breast carcinoma vascularity: a comparison of manual microvessel count and Chalkley count.

    PubMed

    Dhakal, Hari Prasad; Bassarova, Assia; Naume, Bjørn; Synnestvedt, Marit; Borgen, Elin; Kaaresen, Rolf; Schlichting, Ellen; Wiedswang, Gro; Giercksky, Karl-Erik; Nesland, Jahn M

    2009-08-01

    Manual counting of microvessels as intratumoral microvessel density (MVD) and Chalkley counting have been used in several studies to assess the prognostic impact of vascularity in invasive breast carcinomas. In our present study, the aim was to evaluate the prognostic value of angiogenesis in invasive breast carcinoma assessed by MVD and Chalkley techniques in the same series of patients. A total of 498 breast carcinoma patients with median follow up time 85 months were evaluated. The tumour vascularity was quantified by both manual microvessel count (MVD) and Chalkley count in CD34 stained breast carcinoma slides by a single investigator blinded to clinical information. Other relevant clinicopathological parameters were noted, including breast cancer related death and both loco-regional and systemic relapse. The patients were stratified by converting MVD and Chalkley counts to categorical variables to assess prognostic impact, and results were compared. High vascular grades using MVD count did not demonstrate any prognostic significance for breast cancer specific survival (BCSS) or distant disease free survival (DDFS) either in whole patient group (BCSS, p=0.517, DDFS, p=0.301) or in non-treated node negative patients (p>0.05). Chalkley count showed prognostic significance for both DDFS and BCSS in whole patient group (p<0.001) and also in untreated node negative patient group (p<0.05). In multivariate analysis, Chalkley count, but not MVD, retained the prognostic value for BCSS (p=0.007) and DDFS (p=0.014). The Chalkley count for assessing angiogenesis in invasive breast carcinomas demonstrated prognostic value. The Chalkley method appears to be the better method in estimating the prognostic impact of vascularity in invasive breast carcinomas.

  11. Strain energy density and thermodynamic entropy as prognostic measures of crack initiation in aluminum

    NASA Astrophysics Data System (ADS)

    Ontiveros, Victor Luis

    A critical challenge to the continued use of engineering structures as they are asked to perform longer than their design life is the prediction of an initiating crack and the prevention of damage, estimation of remaining useful life, schedule maintenance and to reduce costly downtimes and inspections. The research presented in this dissertation explores the cumulative plastic strain energy density and thermodynamic entropy generation up to crack initiation. Plastic strain energy density and thermodynamic entropy generation are evaluated to investigate whether they would be capable of providing a physical basis for fatigue life and structural risk and reliability assessments. Navy aircraft, specifically, the Orion P-3C, which represent an engineered structure currently being asked to perform past is design life, which are difficult and time consuming to inspect from carrier based operations and are currently evaluated using an empirically based damage index the, fatigue life expended, is used as an example in this investigation. A set of experimental results for aluminum alloy 7075-T651, used in airframe structures, are presented to determine the correlation between plastic strain energy dissipation and the thermodynamic entropy generation versus fatigue crack initiation over a wide range of fatigue loadings. Cumulative plastic strain energy and thermodynamic entropy generation measured from hysteresis energy and temperature rise proved to be valid physical indices for estimation of the probability of crack initiation. Crack initiation is considered as a major evidence of fatigue damage and structural integrity risk. A Bayesian estimation and validation approach is used to determine systematic errors in the developed models as well as other model uncertainties. Comparisons of the energy-based and entropy-based models are presented and benefits of using one over the other are discussed.

  12. Relationship between exploding bridgewire and spark initiation of low density PETN

    NASA Astrophysics Data System (ADS)

    Lee, Elizabeth; Drake, Rod

    2017-01-01

    Recent work has shown that the energy delivered after bridgewire burst affects the function time of an EBW detonator. The spark which is formed post bridgewire burst is the means by which the remaining fireset energy contributes to the reaction. Therefore, by studying the characteristics of spark-gap detonators, insight into the contribution of spark initiation to the functioning of EBW detonators may be achieved. Spark initiation of low density explosives consists of: (i) spark formation, (ii) spark interaction with the bed, and (iii) ignition and growth of reaction. Experiments were performed in which an inert simulant was used to study the formation and propagation of sparks as a function of spark energy. The effect of the spark on inert porous beds was studied over a limited delivered energy range. The disruption of the bed was found to be dependent on the energy delivered. The effect of spark initiation on a low density PETN bed was then examined, the relationship between delivered energy and function time was found to be the same as for EBW detonators.

  13. Trait- and density-mediated indirect interactions initiated by an exotic invasive plant autogenic ecosystem engineer.

    PubMed

    Pearson, Dean E

    2010-10-01

    Indirect interactions are important for structuring ecological systems. However, research on indirect effects has been heavily biased toward top-down trophic interactions, and less is known about other indirect-interaction pathways. As autogenic ecosystem engineers, plants can serve as initiators of nontrophic indirect interactions that, like top-down pathways, can involve both trait-mediated indirect interactions (TMIIs) and density-mediated indirect interactions (DMIIs). Using microcosms, I examined a plant --> predator --> consumer interaction pathway involving the exotic autogenic ecosystem engineer Centaurea maculosa; native Dictyna spiders (which exhibit density and trait [web-building] responses to C. maculosa); Dictyna's insect prey, Urophora affinis; and Urophora's host plant (a secondary receiver species) to quantify DMIIs and TMIIs in an autogenic engineered pathway. Both DMIIs and TMIIs were strong enough to reduce Urophora populations, but only DMIIs, which were 4.3 times stronger than TMIIs, were strong enough to also reduce Urophora's fecundity and increase the fecundity of its host plant. Prior field studies support these results, suggesting that the differences between DMIIs and TMIIs are even stronger in nature. This study illustrates that autogenic ecosystem engineers can initiate powerful indirect interactions that generally parallel predator-initiated interactions but also differ in important functional ways.

  14. Motion of red blood cells near microvessel walls: effects of a porous wall layer

    PubMed Central

    HARIPRASAD, DANIEL S.; SECOMB, TIMOTHY W.

    2013-01-01

    A two-dimensional model is used to simulate the motion and deformation of a single mammalian red blood cell (RBC) flowing close to the wall of a microvessel, taking into account the effects of a porous endothelial surface layer (ESL) lining the vessel wall. Migration of RBCs away from the wall leads to the formation of a cell-depleted layer near the wall, which has a large effect on the resistance to blood flow in microvessels. The objective is to examine the mechanical factors causing this migration, including the effects of the ESL. The vessel is represented as a straight parallel-sided channel. The RBC is represented as a set of interconnected viscoelastic elements, suspended in plasma, a Newtonian fluid. The ESL is represented as a porous medium, and plasma flow in the layer is computed using the Brinkman approximation. It is shown that an initially circular cell positioned close to the ESL in a shear flow is deformed into an asymmetric shape. This breaking of symmetry leads to migration away from the wall. With increasing hydraulic resistivity of the layer, the rate of lateral migration increases. It is concluded that mechanical interactions of RBCs flowing in microvessels with a porous wall layer may reduce the rate of lateral migration and hence reduce the width of the cell-depleted zone external to the ESL, relative to the cell-depleted zone that would be formed if the interface between the ESL and free-flowing plasma were replaced by an impermeable boundary. PMID:23493820

  15. Study of the stability of Z-pinch implosions with different initial density profiles

    SciTech Connect

    Rousskikh, A. G.; Zhigalin, A. S.; Labetskaya, N. A.; Chaikovsky, S. A.; Yushkov, G. Yu.; Oreshkin, V. I.; Batrakov, A. V.; Baksht, R. B.

    2014-05-15

    Stability of metal-puff Z pinches was studied experimentally. Experiments were carried out on a facility producing a load current up to 450 kA with a rise time of 450 ns. In a metal-puff Z pinch, the plasma shell is produced due to evaporation of the electrode material during the operation of a vacuum arc. In the experiment to be reported, a single-shell and a shell-on-jet pinch load with magnesium electrodes were used. Two-dimensional, 3 ns gated, visible-light images were taken at different times during the implosion. When the shell was formed from a collimated plasma flow with small radial divergence, Rayleigh–Taylor (RT) instability typical of gas-puff implosions was recorded. The RT instability was completely suppressed in a mode where the initial density distribution of the shell approached a tailored density profile [A. L. Velikovich et al., Phys. Rev. Lett. 77, 853 (1996)].

  16. Current initiation in low-density foam z-pinch plasmas

    SciTech Connect

    Derzon, M.; Nash, T.; Allshouse, G.

    1996-07-01

    Low density agar and aerogel foams were tested as z-pinch loads on the SATURN accelerator. In these first experiments, we studied the initial plasma conditions by measuring the visible emission at early times with a framing camera and 1-D imaging. At later time, near the stagnation when the plasma is hotter, x-ray imaging and spectral diagnostics were used to characterize the plasma. Filamentation and arcing at the current contacts was observed. None of the implosions were uniform along the z-axis. The prime causes of these problems are believed to be the electrode contacts and the current return configuration and these are solvable. Periodic phenomena consistent with the formation of instabilities were observed on one shot, not on others, implying that there may be a way of controlling instabilities in the pinch. Many of the issues involving current initiation may be solvable. Solutions are discussed.

  17. Reduction of damage initiation density in fused silica optics via UV laser conditioning

    DOEpatents

    Peterson, John E.; Maricle, Stephen M.; Brusasco, Raymond M.; Penetrante, Bernardino M.

    2004-03-16

    The present invention provides a method for reducing the density of sites on the surface of fused silica optics that are prone to the initiation of laser-induced damage, resulting in optics which have far fewer catastrophic defects and are better capable of resisting optical deterioration upon exposure for a long period of time to a high-power laser beam having a wavelength of about 360 nm or less. The initiation of laser-induced damage is reduced by conditioning the optic at low fluences below levels that normally lead to catastrophic growth of damage. When the optic is then irradiated at its high fluence design limit, the concentration of catastrophic damage sites that form on the surface of the optic is greatly reduced.

  18. Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels.

    PubMed

    Yi, Wei; Xu, Hai-tao; Tian, Dao-feng; Wu, Li-quan; Zhang, Shen-qi; Wang, Long; Ji, Bao-wei; Zhu, Xiao-nan; Okechi, Humphrey; Liu, Gang; Chen, Qian-xue

    2015-04-01

    Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.

  19. Constructing and Validating Initial Cα Models from Subnanometer Resolution Density Maps with Pathwalking

    PubMed Central

    Baker, Mariah R.; Rees, Ian; Ludtke, Steven J.; Chiu, Wah; Baker, Matthew L.

    2012-01-01

    A significant number of macromolecular structures solved by electron cryo-microscopy and X-ray crystallography obtain resolutions of 3.5–6Å, at which direct atomistic interpretation is difficult. To address this, we developed pathwalking, a semi-automated protocol to enumerate reasonable Cα models from near-atomic resolution density maps without a structural template or sequence-structure correspondence. Pathwalking uses a novel approach derived from the Traveling Salesman Problem to rapidly generate an ensemble of initial models for individual proteins, which can later be optimized to produce full atomic models. Pathwalking can also be used to validate and identify potential structural ambiguities in models generated from near-atomic resolution density maps. In this work, examples from the EMDB and PDB are used to assess the broad applicability and accuracy of our method. With the growing number of near-atomic resolution density maps from cryo-EM and X-ray crystallography, pathwalking can become an important tool in modeling protein structures. PMID:22405004

  20. Schwann cell interactions with axons and microvessels in diabetic neuropathy.

    PubMed

    Gonçalves, Nádia P; Vægter, Christian B; Andersen, Henning; Østergaard, Leif; Calcutt, Nigel A; Jensen, Troels S

    2017-03-01

    The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annually. The most common complication of diabetes is peripheral neuropathy, which has a prevalence as high as 50% and is characterized by damage to neurons, Schwann cells and blood vessels within the nerve. The pathogenic mechanisms of diabetic neuropathy remain poorly understood, impeding the development of targeted therapies to treat nerve degeneration and its most disruptive consequences of sensory loss and neuropathic pain. Involvement of Schwann cells has long been proposed, and new research techniques are beginning to unravel a complex interplay between these cells, axons and microvessels that is compromised during the development of diabetic neuropathy. In this Review, we discuss the evolving concept of Schwannopathy as an integral factor in the pathogenesis of diabetic neuropathy, and how disruption of the interactions between Schwann cells, axons and microvessels contribute to the disease.

  1. Statistics of initial density perturbations in heavy ion collisions and their fluid dynamic response

    NASA Astrophysics Data System (ADS)

    Floerchinger, Stefan; Wiedemann, Urs Achim

    2014-08-01

    An interesting opportunity to determine thermodynamic and transport properties in more detail is to identify generic statistical properties of initial density perturbations. Here we study event-by-event fluctuations in terms of correlation functions for two models that can be solved analytically. The first assumes Gaussian fluctuations around a distribution that is fixed by the collision geometry but leads to non-Gaussian features after averaging over the reaction plane orientation at non-zero impact parameter. In this context, we derive a three-parameter extension of the commonly used Bessel-Gaussian event-by-event distribution of harmonic flow coefficients. Secondly, we study a model of N independent point sources for which connected n-point correlation functions of initial perturbations scale like 1 /N n-1. This scaling is violated for non-central collisions in a way that can be characterized by its impact parameter dependence. We discuss to what extent these are generic properties that can be expected to hold for any model of initial conditions, and how this can improve the fluid dynamical analysis of heavy ion collisions.

  2. Two-dimensional simulation of red blood cell deformation and lateral migration in microvessels.

    PubMed

    Secomb, Timothy W; Styp-Rekowska, Beata; Pries, Axel R

    2007-05-01

    A theoretical method is used to simulate the motion and deformation of mammalian red blood cells (RBCs) in microvessels, based on knowledge of the mechanical characteristics of RBCs. Each RBC is represented as a set of interconnected viscoelastic elements in two dimensions. The motion and deformation of the cell and the motion of the surrounding fluid are computed using a finite-element numerical method. Simulations of RBC motion in simple shear flow of a high-viscosity fluid show "tank-treading'' motion of the membrane around the cell perimeter, as observed experimentally. With appropriate choice of the parameters representing RBC mechanical properties, the tank-treading frequency and cell elongation agree closely with observations over a range of shear rates. In simulations of RBC motion in capillary-sized channels, initially circular cell shapes rapidly approach shapes typical of those seen experimentally in capillaries, convex in front and concave at the rear. An isolated RBC entering an 8-mum capillary close to the wall is predicted to migrate in the lateral direction as it traverses the capillary, achieving a position near the center-line after traveling a distance of about 60 mum. Cell trajectories agree closely with those observed in microvessels of the rat mesentery.

  3. Effect of viscoelasticity and RBC migration phenomena in stenotic microvessels

    NASA Astrophysics Data System (ADS)

    Dimakopoulos, Yiannis; Syrakos, Alexandros; Georgiou, Georgios; Tsamopoulos, John

    2014-11-01

    This study deals with the numerical simulation of the hemodynamics in stenotic microvessels. The blood flow in microvessels differs significantly from that in large arteries and veins, because the Red Blood Cells (RBCs) are comparable in size with the radius of the microvessels and, consequently, local effects such as cell interaction and migration are more pronounced. In terms of complexity of the flow, viscoelasticity along with stress-gradient induced migration effects have a more dominant role, which exceeds the viscous, inertial and transient effects. Recently, a non-homogeneous viscoelastic model has been proposed by Moyers-Gonzalez et al. (2008), which can accurately predict the Fahraeus effects. We developed a numerical algorithm for the time-integration of the set of differential equations that arise from the coupling of momentum, mass, and population balances for RBCs and aggregates with the constitutive laws for both species. The simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness. Along this layer, the shear stresses are almost Newtonian because of the plasma, but the normal stresses that are exerted on the wall are high due to the contribution of the individual RBCs and rouleaux.

  4. High latitude proton precipitation and light-ion density profiles during the magnetic storm initial phase

    NASA Technical Reports Server (NTRS)

    Burch, J. L.

    1973-01-01

    Measurements of precipitating protons and light ion densities by experiments on OGO-4 indicate that widespread proton precipitation occurs in predawn hours during the magnetic storm initial phase from the latitude of the high-latitude ion trough, or plasmapause , up to Lambda 75 deg. A softening of the proton spectrum is apparent as the plasmapause is approached. The separation of the low-latitude precipitation boundaries for 7.3 kev and 23.8 kev protons is approximately 1 deg, compared with a 3.6 deg separation which has been computed using the formulas of Gendrin and Eather and Carovillano. Consideration of probable proton drift morphology leads to the conclusion that protons ase injected in predawn hours, with widespread precipitation occurring in the region outside the plasmapause. Protons less energetic than approximately 7 kev drift eastward, while the more energetic protons drift westward, producing the observed dawn-dusk asymmetry for the lower-energy protons.

  5. Effect of initial bulk density on high-solids anaerobic digestion of MSW: General mechanism.

    PubMed

    Caicedo, Luis M; Wang, Hongtao; Lu, Wenjing; De Clercq, Djavan; Liu, Yanjun; Xu, Sai; Ni, Zhe

    2017-06-01

    Initial bulk density (IBD) is an important variable in anaerobic digestion since it defines and optimizes the treatment capacity of a system. This study reveals the mechanism on how IBD might affect anaerobic digestion of waste. Four different IBD values: D1 (500-700kgm(-3)), D2 (900-1000kgm(-3)), D3 (1100-1200kgm(-3)) and D4 (1200-1400kgm(-3)) were set and tested over a period of 90days in simulated landfill reactors. The main variables affected by the IBD are the methane generation, saturation degree, extraction of organic matter, and the total population of methanogens. The study identified that IBD >1000kgm(-3) may have significant effect on methane generation, either prolonging the lag time or completely inhibiting the process. This study provides a new understanding of the anaerobic digestion process in saturated high-solids systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Initial Subsurface Incorporation of Oxygen into Ru(0001): A Density Functional Theory Study.

    PubMed

    Cai, Jian-Qiu; Luo, Hai-Jun; Tao, Xiang-Ming; Tan, Ming-Qiu

    2015-12-21

    The adsorption and diffusion of oxygen on Ru(0001) surfaces as a function of coverage are systematically investigated by using density functional theory. A high incorporation barrier of low-coverage adsorbed oxygen into the subsurface is discovered. Calculations show that the adsorption of additional on-surface oxygen can lower the penetration barrier dramatically. The minimum penetration barrier obtained is 1.81 eV for a path starting with oxygen in mixed on-surface hcp and fcc sites at an oxygen coverage of 0.75 ML, which should be regarded as close to 1 ML. Energy diagrams show that oxygen-diffusion barriers on the surface and in the subsurface are much lower than the penetration barrier. Oxygen diffusion on the surface is an indispensable step for its initial incorporation into the subsurface. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Initiation of gametocytogenesis at very low parasite density in Plasmodium falciparum infection

    PubMed Central

    Farid, Ryan; Dixon, Matthew W.; Tilley, Leann

    2017-01-01

    Abstract The recent focus on the elimination of malaria has led to an increased interest in the role of sexual stages in its transmission. We introduce Plasmodium falciparum gametocyte exported protein-5 (PfGEXP5) transcript analysis as an important tool for evaluating the earliest (ring) stage sexual gametocytes in the blood of infected individuals. We show that gametocyte rings are detected in the peripheral blood immediately following establishment of asexual infections—without the need for triggers such as high-density asexual parasitemia or drug treatment. Committed gametocytes are refractory to the commonly used drug piperaquine, and mature gametocytes reappear in the bloodstream 10 days after the initial appearance of gametocyte rings. A further wave of commitment is observed following recrudescent asexual parasitemia, and these gametocytes are again refractory to piperaquine treatment. This work has implications for monitoring gametocyte and transmission dynamics and responses to drug treatment. PMID:28498997

  8. Evidence for top-heavy stellar initial mass functions with increasing density and decreasing metallicity

    NASA Astrophysics Data System (ADS)

    Marks, Michael; Kroupa, Pavel; Dabringhausen, Jörg; Pawlowski, Marcel S.

    2012-05-01

    Residual-gas expulsion after cluster formation has recently been shown to leave an imprint in the low-mass present-day stellar mass function (PDMF) which allowed the estimation of birth conditions of some Galactic globular clusters (GCs) such as mass, radius and star formation efficiency. We show that in order to explain their characteristics (masses, radii, metallicity and PDMF) their stellar initial mass function (IMF) must have been top heavy. It is found that the IMF is required to become more top heavy the lower the cluster metallicity and the larger the pre-GC cloud-core density are. The deduced trends are in qualitative agreement with theoretical expectation. The results are consistent with estimates of the shape of the high-mass end of the IMF in the Arches cluster, Westerlund 1, R136 and NGC 3603, as well as with the IMF independently constrained for ultra-compact dwarf galaxies (UCDs). The latter suggests that GCs and UCDs might have formed along the same channel or that UCDs formed via mergers of GCs. A Fundamental Plane is found which describes the variation of the IMF with density and metallicity of the pre-GC cloud cores. The implications for the evolution of galaxies and chemical enrichment over cosmological times are expected to be major.

  9. Cursorial spiders retard initial aphid population growth at low densities in winter wheat.

    PubMed

    Birkhofer, K; Gavish-Regev, E; Endlweber, K; Lubin, Y D; von Berg, K; Wise, D H; Scheu, S

    2008-06-01

    Generalist predators contribute to pest suppression in agroecosystems. Spider communities, which form a substantial fraction of the generalist predator fauna in arable land, are characterized by two functional groups: web-building and cursorial (non-web-building) species. We investigated the relative impact of these two functional groups on a common pest (Sitobion avenae, Aphididae) in wheat by combining a molecular technique that revealed species-specific aphid consumption rates with a factorial field experiment that analyzed the impact, separately and together, of equal densities of these two spider functional groups on aphid population growth. Only cursorial spiders retarded aphid population growth in our cage experiment, but this effect was limited to the initial aphid-population growth period and low-to-intermediate aphid densities. The molecular analysis, which used aphid-specific primers to detect aphid DNA in predator species, detected the highest proportion of aphid-consuming individuals in two cursorial spiders: the foliage-dwelling Xysticus cristatus (Thomisidae) and the ground-active Pardosa palustris (Lycosidae). The results suggest that manipulating the community composition in favour of pest-consuming functional groups may be more important for improving biological control than fostering predator biodiversity per se. Agricultural management practices that specifically foster effective species or functional groups (e.g. mulching for cursorial spiders) should receive more attention in low-pesticide farming systems.

  10. Shock initiation studies of low density HMX using electromagnetic particle velocity and PVDF stress gauges

    SciTech Connect

    Sheffield, S.A.; Gustavsen, R.L.; Alcon, R.R.; Graham, R.A.; Anderson, M.U.

    1993-09-01

    Magnetic particle velocity and PVDF stress rate gauges have been used to measure the shock response of low density octotetramethylene tetranitramine (HMX) (1.24 &/cm{sup 3}). In experiments done at LANL, magnetic particle velocity gauges were located on both sides of the explosive. In nearly identical experiments done at SNL, PVDF stress rate gauges were located at the same positions so both particle velocity and stress histories were obtained for a particular experimental condition. Unreacted Hugoniot data were obtained and an EOS was developed by combining methods used by Hayes, Sheffield and Mitchell (for describing the Hugoniot of HNS at various densities) with Hermann`s P-{alpha} model. Using this technique, it is only necessary to know some thermodynamic constants or the Hugoniot of the initially solid material and the porous material sound speed to obtain accurate unreacted Hugoniots for the porous explosive. Loading and reaction paths were established in the stress-particle velocity plane for some experimental conditions. This information was used to determine a global reaction rate of {approx} 0.13 {mu}s{sup {minus}1} for porous HMX shocked to 0.8 GPa. At low input stresses the transmitted wave profiles had long rise times (up to 1 {mu}s) due to the compaction processes.

  11. Paedomorphosis in Ambystoma talpoideum: effects of initial body size variation and density.

    PubMed

    Doyle, Jacqueline M; Whiteman, Howard H

    2008-05-01

    Facultative paedomorphosis is the ability of a salamander to either metamorphose into a terrestrial, metamorphic adult or retain a larval morphology to become a sexually mature paedomorphic adult. It has been hypothesized that density and initial body size variation within populations are instrumental in cueing metamorphosis or paedomorphosis in salamanders, yet few studies have adequately tested these hypotheses in long-term experiments. Beginning in the spring of 2004, 36 experimental ponds were used to manipulate three body size variation levels (low, medium, high) and two density levels (low, high) of Ambystoma talpoideum larvae. Larvae were individually marked using visible implant elastomers and collected every 2 weeks in order to measure snout-vent length and mass. Bi-nightly sampling was used to collect new metamorphs as they appeared. Analysis revealed significant effects of density, size variation and morph on body size of individuals during the summer. Individuals that metamorphosed during the fall and following spring were significantly larger as larvae than those becoming paedomorphic across all treatments. These results support the Best-of-a-Bad-Lot hypothesis, which proposes that the largest larvae metamorphose in order to escape unfavorable aquatic habitats. Large larvae may metamorphose to leave aquatic habitats, regardless of treatment, due to the colder climate and lower productivity found in Kentucky, which is in the northern-most part of A. talpoideum's range. By maintaining a long-term experiment, we have provided evidence for the transition of both larvae and paedomorphs into metamorphs during fall and spring metamorphosis events. Furthermore, the production of similar morphs under different environmental conditions observed in this research suggests that the ecological mechanisms maintaining polyphenisms may be more diverse that first suspected.

  12. Self-similar space-time evolution of an initial density discontinuity

    SciTech Connect

    Rekaa, V. L.; Pécseli, H. L.; Trulsen, J. K.

    2013-07-15

    The space-time evolution of an initial step-like plasma density variation is studied. We give particular attention to formulate the problem in a way that opens for the possibility of realizing the conditions experimentally. After a short transient time interval of the order of the electron plasma period, the solution is self-similar as illustrated by a video where the space-time evolution is reduced to be a function of the ratio x/t. Solutions of this form are usually found for problems without characteristic length and time scales, in our case the quasi-neutral limit. By introducing ion collisions with neutrals into the numerical analysis, we introduce a length scale, the collisional mean free path. We study the breakdown of the self-similarity of the solution as the mean free path is made shorter than the system length. Analytical results are presented for charge exchange collisions, demonstrating a short time collisionless evolution with an ensuing long time diffusive relaxation of the initial perturbation. For large times, we find a diffusion equation as the limiting analytical form for a charge-exchange collisional plasma, with a diffusion coefficient defined as the square of the ion sound speed divided by the (constant) ion collision frequency. The ion-neutral collision frequency acts as a parameter that allows a collisionless result to be obtained in one limit, while the solution of a diffusion equation is recovered in the opposite limit of large collision frequencies.

  13. Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment

    PubMed Central

    Tapia, Mónica; Dominguez, Ana; Zhang, Wei; del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José

    2017-01-01

    Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies

  14. Cannabinoid Receptors Modulate Neuronal Morphology and AnkyrinG Density at the Axon Initial Segment.

    PubMed

    Tapia, Mónica; Dominguez, Ana; Zhang, Wei; Del Puerto, Ana; Ciorraga, María; Benitez, María José; Guaza, Carmen; Garrido, Juan José

    2017-01-01

    Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown. In this study, we have focused on the role of the type-1 cannabinoid receptor (CB1R), a highly abundant G-protein coupled receptor (GPCR) in the nervous system largely involved in different phases of neuronal development and differentiation. Although CB1R activity modulation has been related to changes in axons or dendrites, its possible role as a modulator of AIS development has not been yet explored. Here we analyzed the potential role of CB1R on neuronal morphology and AIS development using pharmacological and RNA interference approaches in cultured hippocampal neurons. CB1R inhibition, at a very early developmental stage, has no effect on axonal growth, yet CB1R activation can promote it. By contrast, subsequent dendritic growth is impaired by CB1R inhibition, which also reduces ankyrinG density at the AIS. Moreover, our data show a significant correlation between early dendritic growth and ankyrinG density. However, CB1R inhibition in later developmental stages after dendrites are formed only reduces ankyrinG accumulation at the AIS. In conclusion, our data suggest that neuronal CB1R basal activity plays a role in initial development of dendrites and indirectly in AIS proteins accumulation. Based on the lack of CB1R expression at the AIS, we hypothesize that CB1R mediated modulation of dendritic arbor size during early development indirectly determines the accumulation of ankyrinG and AIS development. Further studies

  15. Cyclooxygenase products stimulate carbon monoxide production by piglet cerebral microvessels.

    PubMed

    Kanu, Alie; Gilpin, David; Fedinec, Alexander L; Leffler, Charles W

    2006-02-01

    Products of arachidonic acid (AA) metabolism by cyclooxygenase (Cox) are important in regulation of neonatal cerebral circulation. The brain and cerebral microvessels also express heme oxygenase (HO) that metabolizes heme to carbon monoxide (CO), biliverdin, and iron. The purpose of this study in newborn pig cerebral microvessels was to address the hypothesis that Cox products affect HO activity and HO products affect Cox activity. AA (2.0-20 microM) increased prostaglandin E2 (PGE2) measured by radioimmunoassay (RIA) and also CO measured by gas chromatography/mass spectrometry (GC/MS). Further, 10(-4) M indomethacin, which inhibited Cox, reduced both AA and heme-induced CO production. Conversely, neither exogenous 2 x 10(-6) M heme, which markedly increased CO production, nor the inhibitor of HO, chromium mesoporphyrin, altered PGE2 synthesis. Because AA metabolism by Cox generates both prostanoids and superoxides, we determined the effects of the predominant prostanoid and superoxide on CO production. Although PGE2 caused a small increase in CO production, xanthine oxidase plus hypoxanthine, which produces superoxide, strongly stimulated the production of CO by cerebral microvessels. This increase was mildly attenuated by catalase. These data suggest that Cox-catalyzed AA metabolites, most likely superoxide and/or a subsequent reactive oxygen species, increase cerebrovascular CO production. This increase seems to be caused, at least in part, by the elevation of HO-2 catalytic activity. Conversely, Cox activity is not affected by HO-catalyzed heme metabolites. These data suggest that some cerebrovascular functions attributable to Cox activity could be mediated by CO.

  16. Permeability of disrupted cerebral microvessels in the frog.

    PubMed

    Fraser, P A; Dallas, A D

    1993-02-01

    1. This study reports the results of varying the hydrostatic pressure on measurements of permeability coefficient to the low molecular weight impermeant dye carboxyfluorescein (MW = 376) in single leaky cerebral microvessels. A mathematical model, that solved the convective diffusion equations used to analyse the measurements, showed that the measurements were consistent with leakiness being due to 22 nm wide parallel-sided slits between endothelial cells. 2. Microvessels on the surface of the frog's brain were cannulated with a micropipette and perfused with an artificial cerebrospinal fluid containing the dye. Vessels were occluded with a glass microneedle and the rate of change in dye concentration in a 12 microns length section was measured using video-intensified microscopy. 3. It was found that the rate of dye loss at all points along the occluded microvessel segment could be accounted for by a model for convection and diffusion, and that changes in dye concentration at a point remote from the segment entrance can give a good measure of diffusive permeability. 4. When series of measurements were carried out on a single vessel, permeability rose over the course of 20 min. Mean permeability for all measurements was 3.01 x 10(-5) cm sec-1, n = 64 (mode, 2.0; range, 0.48-9.6). The hydrostatic pressure applied during the perfusion had no effect on the measured permeability. 5. The dye concentration along the vessel axis was measured at the steady state and was shown to respond to changes in hydrostatic perfusion pressure in a way predicted by the model. This indicates that hydrostatically driven bulk flow can be important, and thus convection may account for effects previously ascribed to vesicular transcytosis. 6. The possible anatomical basis for the porous pathway is discussed in the light of recent observations on the presence of 0.5 microns perijunctional gaps, the possibility of transendothelial channels, and the unzipping of tight junctions to leave a 22 nm

  17. CYCLOOXYGENASE PRODUCTS STIMULATE CARBON MONOXIDE PRODUCTION BY PIGLET CEREBRAL MICROVESSELS

    PubMed Central

    Kanu, Alie; Gilpin, David; Fedinec, Alexander L.

    2005-01-01

    Products of arachidonic acid (AA) metabolism by cyclooxygenase (COX) are important in regulation of neonatal cerebral circulation. The brain and cerebral microvessels also express heme oxygenase (HO) that metabolizes heme to carbon monoxide (CO), biliverdin, and iron. The purpose of this study in newborn pig cerebral microvessels was to address the hypothesis that COX products affect HO activity and HO products affect COX activity. AA (2.0-20μM) increased PGE2 measured by RIA and also CO measured by gas chromatography/mass spectrometry (GC-MS). Further, indomethacin (10-4M), that inhibited COX, reduced both AA and heme-induced CO production. Conversely, neither exogenous heme (2×10-6M), that markedly increased CO production, nor the inhibitor of HO, chromium mesoporphyrin, altered PGE2 synthesis. Because AA metabolism by COX generates both prostanoids and superoxides, we determined the effects of the predominant prostanoid and superoxide on CO production. While PGE2 caused a small increase in CO production, xanthine oxidase plus hypoxanthine that produces superoxide strongly stimulated the production of CO by cerebral microvessels. This increase was mildly attenuated by catalase. These data suggest that COX catalyzed AA metabolite(s), most likely superoxide, H2O2, and / or a subsequent reactive oxygen species increases cerebrovascular CO production. This increase appears to be due, at least in part, to the elevation of HO-2 catalytic activity. Conversely, COX activity is not affected by HO-catalyzed heme metabolites. These data suggest that some cerebrovascular functions attributable to COX activity could be mediated by CO. PMID:16446494

  18. Initial density fluctuation measurements from the NSTX Beam Emission Spectroscopy diagnostic system*

    NASA Astrophysics Data System (ADS)

    Smith, D. R.; Fonck, R. J.; McKee, G. R.; Schoenbeck, N. L.; Thompson, D.; Uzun-Kaymak, I. U.; Stratton, B. C.

    2010-11-01

    Density fluctuation measurements on the ion gyroscale have been obtained on NSTX with a newly commissioned beam emission spectroscopy (BES) diagnostic system. The BES system measures red-shifted Dα emission near 660 nm from deuterium neutral beams with high throughput optics and high efficiency detectors. The system presently employs 16 detection channels arranged in radial and poloidal arrays, and an expansion to 32 channels is planned. Radial arrays can measure fluctuations from r/a 0.1 to beyond the last closed flux surface and resolve fluctuations with kρi<=1.5. Initial BES measurements reveal broadband turbulence and coherent modes below 300 kHz for r/a>=0.4. The broadband turbulence appears in high gradient regions and increases at H-L transitions. The frequency characteristics of the coherent modes correlate with Alfvén/energetic particle modes in Mirnov probe measurements, but some coherent modes appear in BES measurements only. *Supported by the U.S. Department of Energy under Contract Nos. DE-FG02-89ER53296, DE-AC02-09CH11466 and DE-SC0001288.

  19. Effect of initial densities in the lattice Boltzmann model for non-ideal fluid with curved interface

    NASA Astrophysics Data System (ADS)

    Gong, Jiaming; Oshima, Nobuyuki

    2017-06-01

    The effect of initial densities in a free energy based two-phase-flow lattice Boltzmann method for non-ideal fluids with a curved interface was investigated in the present work. To investigate this effect, the initial densities in the liquid and gas phases coming from the saturation points and the equilibrium state were adopted in the simulation of a static droplet in an open and a closed system. For the purpose of simplicity and easier comparison, the closed system is fabricated by the implementation of the periodic boundary condition at the inlet and outlet of a gas channel, and the open system is fabricated by the implementation of a constant flux boundary condition at the inlet and a free-out boundary condition at the outlet of the same gas channel. By comparing the simulation results from the two types of initial densities in the open and closed systems, it is proven that the commonly used saturation initial densities setting is the reason for droplet mass and volume variation which occurred in the simulation, particularly in the open system with a constant flux boundary condition. Such problems are believed to come from the curvature effect of the surface tension and can be greatly reduced by adopting the initial densities in the two phases from equilibrium state.

  20. Initial glenoid fixation using two different reverse shoulder designs with an equivalent center of rotation in a low-density and high-density bone substitute.

    PubMed

    Stroud, Nicholas J; DiPaola, Matthew J; Martin, Brian L; Steiler, Cindy A; Flurin, Pierre-Henri; Wright, Thomas W; Zuckerman, Joseph D; Roche, Christopher P

    2013-11-01

    Numerous glenoid implant designs have been introduced into the global marketplace in recent years; however, little comparative biomechanical data exist to substantiate one design consideration over another. This study dynamically evaluated reverse shoulder glenoid baseplate fixation and compared the initial fixation associated with 2 reverse shoulder designs having an equivalent center of rotation in low-density and high-density bone substitute substrates. Significant differences in fixation were observed between implant designs, where the circular-porous reverse shoulder was associated with approximately twice the micromotion per equivalent test than the oblong-grit-blasted design. Additionally, 6 of the 7 circular-porous reverse shoulders failed catastrophically in the low-density bone model at an average of 2603 ± 981 cycles. None of the oblong-grit-blasted designs failed in the low-or high-density bone models and none of the circular-porous designs failed in the high-density bone models after 10,000 cycles of loading. These results demonstrate that significant differences in initial fixation exist between reverse shoulder implants having an equivalent center of rotation and suggest that design parameters, other than the position of the center of rotation, significantly affect fixation in low-density and high-density polyurethane bone substitutes. Subtle changes in glenoid baseplate design can dramatically affect fixation, particularly in low-density bone substitutes that are intended to simulate the bone quality of the recipient population for reverse shoulders. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  1. The proteome of mouse brain microvessel membranes and basal lamina

    PubMed Central

    Chun, Hyun Bae; Scott, Michael; Niessen, Sherry; Hoover, Heather; Baird, Andrew; Yates, John; Torbett, Bruce E; Eliceiri, Brian P

    2011-01-01

    The blood–brain barrier (BBB) is a multicellular vascular structure separating blood from the brain parenchyma that is composed of endothelial cells with tight intercellular junctions, surrounded by a basal lamina, astrocytes, and pericytes. Previous studies have generated detailed databases of the microvessel transcriptome; however, less information is available on the BBB at the protein level. In this study, we specifically focused on characterization of the membrane fraction of cells within the BBB to generate a more complete understanding of membrane transporters, tight junction proteins, and associated extracellular matrix proteins that are functional hallmarks of the BBB. We used Multidimensional Protein Identification Technology to identify a total of 1,143 proteins in mouse brain microvessels, of which 53% were determined to be membrane associated. Analyses of specific classes of BBB-associated proteins in the context of recent transcriptome reports provide a unique database to assess the relative contribution of genes at the level of both RNA and protein in the maintenance of normal BBB integrity. PMID:21792245

  2. Magnetic resonance imaging of microvessels using iron-oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Olamaei, N.; Cheriet, F.; Martel, S.

    2013-03-01

    The visualization of microstructures including blood vessels with an inner overall cross-sectional area below approximately 200 μm remains beyond the capabilities of current clinical imaging modalities. But with magnetic resonance (MR) imaging, magnetic entities cause susceptibility artifacts in the images by disrupting the homogeneous magnetic field in a much larger scale than their actual size. As validated in this paper through simulation and in-vitro experiments, these artifacts can serve as a source of contrast, enabling microvessels with an inner diameter below the spatial resolution of any medical imaging modalities to be visualized using a clinical MR scanner. For such experiments, micron-sized agglomerations of iron-oxide (Fe3O4) nanoparticles were injected in microchannels with internal diameters of 200 and 50 μm equivalent to a narrower artery or a larger arteriole, and down to a smaller arteriole, respectively. The results show the feasibility of the proposed method for micro-particle detection and the visualization of microvessels using a 1.5 T clinical MR scanner. It was confirmed that the method is reproducible and accurate at the sub-pixel level.

  3. Quantitative study on appearance of microvessels in spectral endoscopic imaging

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Hiroshi; Saito, Takaaki; Shiraishi, Yasushi; Arai, Fumihito; Morimoto, Yoshinori; Yuasa, Atsuko

    2015-03-01

    Increase in abnormal microvessels in the superficial mucosa is often relevant to diagnostic findings of neoplasia in digestive endoscopy; hence, observation of superficial vasculature is crucial for cancer diagnosis. To enhance the appearance of such vessels, several spectral endoscopic imaging techniques have been developed, such as narrow-band imaging and blue laser imaging. Both techniques exploit narrow-band blue light for the enhancement. The emergence of such spectral imaging techniques has increased the importance of understanding the relation of the light wavelength to the appearance of superficial vasculature, and thus a new method is desired for quantitative analysis of vessel visibility in relation to the actual structure in the tissue. Here, we developed microvessel-simulating phantoms that allowed quantitative evaluation of the appearance of 15-μm-thick vessels. We investigated the relation between the vascular contrast and light wavelength by the phantom measurements and also verified it in experiments with swine, where the endoscopically observed vascular contrast was investigated together with its real vascular depth and diameter obtained by microscopic observation of fluorescence-labeled vessels. Our study indicates that changing the spectral property even in the wavelength range of blue light may allow selective enhancement of the vascular depth for clinical use.

  4. THE INITIAL MASS FUNCTION AND THE SURFACE DENSITY PROFILE OF NGC 6231

    SciTech Connect

    Sung, Hwankyung; Sana, Hugues; Bessell, Michael S. E-mail: H.Sana@uva.nl

    2013-02-01

    We have performed new wide-field photometry of the young open cluster NGC 6231 to study the shape of the initial mass function (IMF) and mass segregation. We also investigated the reddening law toward NGC 6231 from optical to mid-infrared color excess ratios, and found that the total-to-selective extinction ratio is R{sub V} = 3.2, which is very close to the normal value. But many early-type stars in the cluster center show large color excess ratios. We derived the surface density profiles of four member groups, and found that they reach the surface density of field stars at about 10', regardless of stellar mass. The IMF of NGC 6231 is derived for the mass range 0.8-45 M{sub Sun }. The slope of the IMF of NGC 6231 ({Gamma} = -1.1 {+-} 0.1) is slightly shallower than the canonical value, but the difference is marginal. In addition, the mass function varies systematically, and is a strong function of radius-it is very shallow at the center, and very steep at the outer ring suggesting the cluster is mass segregated. We confirm the mass segregation for the massive stars (m {approx}> 8 M{sub Sun }) by a minimum spanning tree analysis. Using a Monte Carlo method, we estimate the total mass of NGC 6231 to be about 2.6 ({+-} 0.6) Multiplication-Sign 10{sup 3} M{sub Sun }. We constrain the age of NGC 6231 by comparison with evolutionary isochrones. The age of the low-mass stars ranges from 1 to 7 Myr with a slight peak at 3 Myr. However, the age of the high-mass stars depends on the adopted models and is 3.5 {+-} 0.5 Myr from the non-rotating or moderately rotating models of Brott et al. as well as the non-rotating models of Ekstroem et al. But the age is 4.0-7.0 Myr if the rotating models of Ekstroem et al. are adopted. This latter age is in excellent agreement with the timescale of ejection of the high-mass runaway star HD 153919 from NGC 6231, albeit the younger age cannot be entirely excluded.

  5. Beetle and plant density as cues initiating dispersal in two species of adult predaceous diving beetles.

    PubMed

    Yee, Donald A; Taylor, Stacy; Vamosi, Steven M

    2009-05-01

    Dispersal can influence population dynamics, species distributions, and community assembly, but few studies have attempted to determine the factors that affect dispersal of insects in natural populations. Consequently, little is known about how proximate factors affect the dispersal behavior of individuals or populations, or how an organism's behavior may change in light of such factors. Adult predaceous diving beetles are active dispersers and are important predators in isolated aquatic habitats. We conducted interrelated studies to determine how several factors affected dispersal in two common pond-inhabiting species in southern Alberta, Canada: Graphoderus occidentalis and Rhantus sericans. Specifically, we (1) experimentally tested the effect of plant and beetle densities on dispersal probabilities in ponds; (2) surveyed ponds and determined the relationships among beetle densities and plant densities and water depth; and (3) conducted laboratory trials to determine how beetle behavior changed in response to variation in plant densities, conspecific densities, food, and water depth. Our field experiment determined that both species exhibited density dependence, with higher beetle densities leading to higher dispersal probabilities. Low plant density also appeared to increase beetle dispersal. Consistent with our experimental results, densities of R. sericans in ponds were significantly related to plant density and varied also with water depth; G. occidentalis densities did not vary with either factor. In the laboratory, behavior varied with plant density only for R. sericans, which swam at low density but were sedentary at high density. Both species responded to depth, with high beetle densities eliciting beetles to spend more time in deeper water. The presence of food caused opposite responses for G. occidentalis between experiments. Behavioral changes in response to patch-level heterogeneity likely influence dispersal in natural populations and are expected

  6. Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study1234

    PubMed Central

    Orchard, Tonya S; Larson, Joseph C; Alghothani, Nora; Bout-Tabaku, Sharon; Cauley, Jane A; Chen, Zhao; LaCroix, Andrea Z; Wactawski-Wende, Jean; Jackson, Rebecca D

    2014-01-01

    Background: Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear. Objective: We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD). Design: This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants. Results: Baseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with <206.5 mg Mg/d. However, the incidence and RR of hip and total fractures did not differ across quintiles of magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend < 0.001]. Conclusions: Lower magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls. This trial was registered at clinicaltrials.gov as NCT00000611. PMID:24500155

  7. The dynamics of superclusters - Initial determination of the mass density of the universe at large scales

    NASA Technical Reports Server (NTRS)

    Ford, H. C.; Ciardullo, R.; Harms, R. J.; Bartko, F.

    1981-01-01

    The radial velocities of cluster members of two rich, large superclusters have been measured in order to probe the supercluster mass densities, and simple evolutionary models have been computed to place limits upon the mass density within each supercluster. These superclusters represent true physical associations of size of about 100 Mpc seen presently at an early stage of evolution. One supercluster is weakly bound, the other probably barely bound, but possibly marginally unbound. Gravity has noticeably slowed the Hubble expansion of both superclusters. Galaxy surface-density counts and the density enhancement of Abell clusters within each supercluster were used to derive the ratio of mass densities of the superclusters to the mean field mass density. The results strongly exclude a closed universe.

  8. The dynamics of superclusters - Initial determination of the mass density of the universe at large scales

    NASA Technical Reports Server (NTRS)

    Ford, H. C.; Ciardullo, R.; Harms, R. J.; Bartko, F.

    1981-01-01

    The radial velocities of cluster members of two rich, large superclusters have been measured in order to probe the supercluster mass densities, and simple evolutionary models have been computed to place limits upon the mass density within each supercluster. These superclusters represent true physical associations of size of about 100 Mpc seen presently at an early stage of evolution. One supercluster is weakly bound, the other probably barely bound, but possibly marginally unbound. Gravity has noticeably slowed the Hubble expansion of both superclusters. Galaxy surface-density counts and the density enhancement of Abell clusters within each supercluster were used to derive the ratio of mass densities of the superclusters to the mean field mass density. The results strongly exclude a closed universe.

  9. Self-gravitating compressible Maxwell Earth models: the role of the self compression and the compositional initial density gradient

    NASA Astrophysics Data System (ADS)

    Cambiotti, G.

    2009-04-01

    We analyse a new class of self-gravitating Maxwell Earth models that takes the compressibility into account both at the initial state of hydrostatic equilibrium and during the deformations. By resorting to the Correspondence Principle we derive the analytical solution for a particular model with an inviscid core, a Darwin law density profile in the mantle and a continuous compositional initial density gradient. It allows to gain deep insight into the global dynamics of the Earth showing that the compressional stratification is responsible only for stable modes, namely the C0 and M0 buoyancy modes, the D-modes and the transient modes, while the compositional stratification triggers new transient modes and a denumerably set of buoyancy modes, of which the RT-modes are a particular case. We show that the model is unstable only when the square of the Brunt-Väiäsala frequency is positive and the solely unstable modes are the new compositional ones. By resorting to a numerical algorithm we extend our analysis to more general self-compressed compressible models with specific Darwin law density profiles in each layer and a compositional initial density gradient describing the density contrasts at the main Earth interfaces. We show that no buoyancy modes are due to the continuous variation of the initial density but they arise because of the density contrasts while the D-modes are substitute by a non-modal contribution always associated with the compressional relaxation times. Such results shed light on the role of the compositional stratification on the relaxation processes and allow us to deal with the issue of the Earth stability in a more consistent way compared to the past. Besides this they are relevant to model the Post-Glacial rebound and the post seismic deformations.

  10. On peculiarities of near-threshold initiation of powder density explosive by air shock wave and by solid impactor

    NASA Astrophysics Data System (ADS)

    Kashkarov, AO; Ershov, AP; Pruuel, ER

    2016-10-01

    The features of near-threshold mode of initiating by gas-tight piston and high- enthalpy gas flow was evaluated for a powder density explosive PETN. Both methods lead to the development of detonation in about 10 μs time. The synchrotron radiation diagnostics have shown that the initial stages of the process were significantly different, that diversity being caused by the influence of the gas flow in the pores of the charge. In this work, the effect of the gas flow on the mode of initiation was studied experimentally.

  11. Relation of initial spacing and relative stand density indices to stand characteristics in a Douglas-fir plantation spacing trial

    Treesearch

    Robert O. Curtis; Sheel Bansal; Constance A. Harrington

    2016-01-01

    This report presents updated information on a 1981 Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii ) plantation spacing trial at 33 years from planting. Stand statistics at the most recent measurement were compared for initial spacing of 1 through 6 meters and associated relative densities. There was no clear...

  12. Microvessel Landscape Assessment in Pancreatic Ductal Adenocarcinoma: Unclear Value of Targeting Endoglin (CD105) as Prognostic Factor of Clinical Outcome.

    PubMed

    Lytras, Dimitrios; Leontara, Vassileia; Kefala, Maria; Foukas, Periklis G; Giannakou, Niki; Pouliakis, Abraham; Dervenis, Christos; Panayiotides, Ioannis G; Karakitsos, Petros

    2015-01-01

    Tumor angiogenesis based on microvessel density assessment has been associated with poor prognosis in several studies of patients with pancreatic ductal adenocarcinoma (PDAC). Expression of endoglin (CD105), a tumor-induced vascularization marker, has been found to represent a negative prognostic factor in many malignant tumors. The aim of our study was to assess the value of tumoral microvascularity both with pan-endothelial markers and endoglin as well, in correlation with the clinical outcome of patients with PDAC. Fifty-eight patients with PDAC, 36 males and 22 females, with a mean (SD) age of 65.4 (10.0) years were included in the study. Deparaffinized sections from formalin-fixed areas both from the center and periphery (invasion front) of the tumors were immunostained for CD105 as well as for the endothelial markers CD31 and CD34. Tumoral angiogenesis was assessed on the basis of microvessel density (number of vessels per square millimeter) and on microvascular area (square micrometers) as well. High intratumoral microvascular area, in endoglin-stained sections, was found to be of marginal prognostic significance for recurrence (log rank, P 0.05). Survival was also marginally associated with CD31 intratumoral microvascular area (log rank, P 0.05). Further studies are needed before endoglin replaces the conventional angiogenesis markers in PDCA.

  13. Relation of initial spacing and relative stand density indices to stand characteristics in a Douglas-fir plantation spacing trial

    USGS Publications Warehouse

    Curtis, Robert O.; Bansal, Sheel; Harrington, Constance A.

    2016-01-01

    This report presents updated information on a 1981 Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii) plantation spacing trial at 33 years from planting. Stand statistics at the most recent measurement were compared for initial spacing of 1 through 6 meters and associated relative densities. There was no clear relationship of spacing to top height. Diameter, live crown ratio, and percent survival increased with spacing; basal area and relative density decreased with increase in spacing. Volume in trees ≥ 4 cm diameter was greatest at 2 m spacing, while utilizable volume (trees ≥20 cm dbh) was greatest at 4 m spacing. Live crown ratio decreased and total crown projectional area increased with increasing relative density indices. Total crown projectional area was more closely related to relative density than to basal area.

  14. Social behaviour involving drug resistance: the role of initial density, initial frequency and population structure in shaping the effect of antibiotic resistance as a public good.

    PubMed

    Domingues, I L; Gama, J A; Carvalho, L M; Dionisio, F

    2017-06-21

    Bacteria sometimes cooperate with co-inhabiting cells. Pathogenic bacteria, for example, often produce and excrete virulence factors, eventually benefitting both producer and non-producer cells. The role of social interactions involving antibiotic resistance, however, has been more elusive. Enzymes that inactivate β-lactam antibiotics such as ampicillin or penicillin (β-lactamases) are good candidates as public goods. Nonetheless, it has been claimed that bacteria harbouring plasmids of natural origin coding for β-lactamase almost do not protect sensitive bacteria. This does not fit with the fact that ampicillin-sensitive bacteria can be isolated from subjects undergoing ampicillin treatment. We hypothesised that there are two non-exclusive explanations for the discrepancy between previous works: (1) the range of values of demographic conditions (such as initial strain frequency, initial total cell density or habitat structure) has not been broad enough to include most scenarios, or (2) there are interactions between some of these factors. We performed experiments with Escherichia coli bacterial cells to measure the degree of protection of sensitive cells when co-cultured with cells harbouring RP4, R16a or the R1 plasmids, all of natural origin and coding for β-lactamases, and in presence of ampicillin. In these co-cultures, performed in structured and non-structured environments, both the initial total cell density and the initial frequency of sensitive cells spanned four orders of magnitude. We found protection of sensitive cells in 63% of tested conditions. All factors (plasmid, structure, frequency and density) significantly affect levels of protection. Moreover, all factors interact, with interactions revealing large or very large effect sizes.Heredity advance online publication, 21 June 2017; doi:10.1038/hdy.2017.33.

  15. Effect of Initial Nematode Population Density on the Interaction of Pratylenchus penetrans and Verticillium dahliae on 'Russet Burbank' Potato

    PubMed Central

    Saeed, I. A. M.; MacGuidwin, A. E.; Rouse, D. I.

    1998-01-01

    Four similar growth chamber experiments were conducted to test the hypothesis that the initial population density (Pi) of Pratylenchus penetrans influences the severity of interactive effects of P. penetrans and Verticillium dahliae on shoot growth, photosynthesis, and tuber yield of Russet Burbank potato. In each experiment, three population densities of P. penetrans with and without concomitant inoculation with V. dahliae were compared with nematode-free controls. The three specific Pi of JR penetrans tested varied from experiment to experiment but fell in the ranges 0.8-2.5, 1.8-3.9, 2.1-8.8, and 7.5-32.4 nematodes/cm³ soil. Inoculum of V. dahliaewas mixed into soil, and the assayed density was 5.4 propagules/gram dry soil. Plants were grown 60 to 80 days in a controlled environment. Plant growth parameters in two experiments indicated significant interactions between P. penetrans and V. dahliae. In the absence of V. dahliae, P. penetrans did not reduce plant growth and tuber yield below that of the nematode-free control or did so only at the highest one or two population densities tested. In the presence of K dahliae, the lowest population density significantly reduced shoot weight and photosynthesis in three and four experiments, respectively. Higher densities had no additional effect on shoot weight and caused additional reductions in photosynthesis in only one experiment. Population densities of 0.8 and 7.5 nematodes/cm³ soil reduced tuber yield by 51% and 45%, whereas higher densities had no effect or a 15% additional effect, respectively. These data indicate that interactive effects between P. penetrans and V. dahliae on Russet Burbank potato are manifested at P. penetrans population densities less than 1 nematode/cm³ soil and that the nematode population density must be substantially higher before additional effects are apparent. PMID:19274204

  16. Widefield in vivo spectral and fluorescence imaging microscopy of microvessel blood supply and oxygenation

    NASA Astrophysics Data System (ADS)

    Lee, Jennifer; Kozikowski, Raymond; Wankhede, Mamta; Sorg, Brian S.

    2011-02-01

    Abnormal microvascular function and angiogenesis are key components of various diseases that can contribute to the perpetuation of the disease. Several skin diseases and ophthalmic pathologies are characterized by hypervascularity, and in cancer the microvasculature of tumors is structurally and functionally abnormal. Thus, the microvasculature can be an important target for treatment of diseases characterized by abnormal microvasculature. Motivated largely by cancer research, significant effort has been devoted to research on drugs that target the microvasculature. Several vascular targeting drugs for cancer therapy are in clinical trials and approved for clinical use, and several off-label uses of these drugs have been reported for non-cancer diseases. The ability to image and measure parameters related to microvessel function preclinically in laboratory animals can be useful for development and comparison of vascular targeting drugs. For example, blood supply time measurements give information related to microvessel morphology and can be measured with first-pass fluorescence imaging. Hemoglobin saturation measurements give an indication of microvessel oxygen transport and can be measured with spectral imaging. While each measurement individually gives some information regarding microvessel function, the measurements together may yield even more information since theoretically microvessel morphology can influence microvessel oxygenation, especially in metabolically active tissue like tumors. However, these measurements have not yet been combined. In this study, we report the combination of blood supply time imaging and hemoglobin saturation imaging of microvessel networks in tumors using widefield fluorescence and spectral imaging, respectively. The correlation between the measurements in a mouse mammary tumor is analyzed.

  17. The Effect of Air Density on Atmospheric Electric Fields Required for Lightning Initiation from a Long Airborne Object

    NASA Technical Reports Server (NTRS)

    Bazelyan, E. M.; Aleksandrov, N. L.; Raizer, Yu. Pl.; Konchankov, A. M.

    2006-01-01

    The purpose of the work was to determine minimum atmospheric electric fields required for lightning initiation from an airborne vehicle at various altitudes up to 10 km. The problem was reduced to the determination of a condition for initiation of a viable positive leader from a conductive object in an ambient electric field. It was shown that, depending on air density and shape and dimensions of the object, critical atmospheric fields are governed by the condition for leader viability or that for corona onset. To establish quantitative criteria for reduced air densities, available observations of spark discharges in long laboratory gaps were analyzed, the effect of air density on leader velocity was discussed and evolution in time of the properties of plasma in the leader channel was numerically simulated. The results obtained were used to evaluate the effect of pressure on the quantitative relationships between the potential difference near the leader tip, leader current and its velocity; based on these relationships, criteria for steady development of a leader were determined for various air pressures. Atmospheric electric fields required for lightning initiation from rods and ellipsoidal objects of various dimensions were calculated at different air densities. It was shown that there is no simple way to extend critical ambient fields obtained for some given objects and pressures to other objects and pressures.

  18. Endothelial cell shrinkage increases permeability through a Ca2+-dependent pathway in single frog mesenteric microvessels

    PubMed Central

    Kajimura, M; Curry, F E

    1999-01-01

    We tested whether calcium (Ca2+)-dependent mechanisms were essential for our previous observation that a change in the endothelial cell (EC)-extracellular matrix (ECM) attachment caused an increase in microvessel hydraulic permeability (Lp) after exposure to hypertonic solutions in single perfused mesenteric microvessels in pithed frogs (Rana pipiens). In microvessels where integrin-dependent EC-ECM attachments were disrupted by pretreatment with the peptide Gly-Arg-Gly-Asp-Thr-Pro (GRGDTP; 0·3 mmol l−1), we measured microvessel Lp after exposure to hypertonic solutions under experimental conditions that reduced Ca2+ influx into endothelial cells. High K+ solutions (59·7 and 100 mmol l−1 K+) were used to depolarize the endothelial membrane and therefore to reduce the electrochemical driving force for Ca2+ influx through conductive Ca2+ channels. These solutions abolished the increase in Lp caused by hypertonic solutions in the microvessels pretreated with GRGDTP. We previously suggested that the removal of albumin from the perfusate may reduce EC-ECM attachment because hypertonic solutions increased the Lp of microvessels above that due to removal of albumin alone. This additional increase in Lp was attenuated by the 59·7 mmol l−1 K+ solution and was completely abolished by the 100 mmol l−1 K+ solution. Bumetanide, an inhibitor of the Na+-K+-2Cl− co-transporter and one of the mechanisms of regulatory volume increase after exposure to hypertonic solutions in endothelial cells, did not change the response of microvessels to high K+ solutions. Our findings indicate that Ca2+ entry into endothelial cells via passive conductance channels is necessary to increase microvessel Lp after exposure to hypertonic solutions in microvessels where EC-ECM attachments are disrupted. PMID:10373704

  19. Reactive flow modeling of initial density effect on divergence JB-9014 detonation driving

    NASA Astrophysics Data System (ADS)

    Yu, Xin; Huang, Kuibang; Zheng, Miao

    2016-06-01

    A serious of experiments were designed and the results were represented in this paper, in which 2mm thickness cooper shells were impacted by explosives named JB-9014 with different densities, and the surface velocities of the OFHC shells were measured. The comparison of experimental data shows the free surface velocity of the OFHC shell increase with the IHE density. Numerical modeling, which occupied phenomenological reactive flow rate model using the two-dimensional Lagrange hydrodynamic code, were carried out to simulate the above experiments, and empirical adjustments on detonation velocity and pressure and Pier Tang's adjustments on EOS of detonation products were both introduced in our numerical simulation work. The computational results agree well with that of experiments, and the numerical results with original parameters of products and the adjusted ones of JB-9014 could describe the density effect distinctly.

  20. Reactive flow modeling of initial density effect on divergence JB-9014 detonation driving

    SciTech Connect

    Yu, Xin Huang, Kuibang; Zheng, Miao

    2016-06-08

    A serious of experiments were designed and the results were represented in this paper, in which 2 mm thickness cooper shells were impacted by explosives named JB-9014 with different densities, and the surface velocities of the OFHC shells were measured. The comparison of experimental data shows the free surface velocity of the OFHC shell increase with the IHE density. Numerical modeling, which occupied phenomenological reactive flow rate model using the two-dimensional Lagrange hydrodynamic code, were carried out to simulate the above experiments, and empirical adjustments on detonation velocity and pressure and Pier Tang’s adjustments on EOS of detonation products were both introduced in our numerical simulation work. The computational results agree well with that of experiments, and the numerical results with original parameters of products and the adjusted ones of JB-9014 could describe the density effect distinctly.

  1. Initial development of a new empirical model of the earth's inner magnetosphere for density, temperature, and composition

    NASA Technical Reports Server (NTRS)

    Gallagher, D. L.; Craven, P. D.

    1988-01-01

    The analytical representation of plasma characteristics in the near earth environment is a valuable tool for studying wave propagation, for new instrument and spacecraft design, and for developing a better theoretical understanding of plasmaspheric processes. There are no empirical models currently available that encompass the near-earth environment and include the core or low-energy plasma characteristic of that region. The initial steps to constructing a new empirical model of plasmaspheric density, temperature, and composition are discussed. A limited set of density measurements from the retarding ion mass spectrometer and the plasma wave instrument on the Dynamics Explorer 1 spacecraft is used to demonstrate features of the proposed analytical formalism.

  2. Late-Time Mixing Sensitivity to Initial Broadband Surface Roughness in High-Energy-Density Shear Layers

    DOE PAGES

    Flippo, K. A.; Doss, F. W.; Kline, J. L.; ...

    2016-11-23

    While using a large volume high-energy-density fluid shear experiment ( 8.5 cm 3 ) at the National Ignition Facility, we have demonstrated for the first time the ability to significantly alter the evolution of a supersonic sheared mixing layer by controlling the initial conditions of that layer. Furthermore, by altering the initial surface roughness of the tracer foil, we demonstrate the ability to transition the shear mixing layer from a highly ordered system of coherent structures to a randomly ordered system with a faster growing mix layer, indicative of strong mixing in the layer at a temperature of several tensmore » of electron volts and at near solid density. Moreover, simulations using a turbulent-mix model show good agreement with the experimental results and poor agreement without turbulent mix.« less

  3. Late-Time Mixing Sensitivity to Initial Broadband Surface Roughness in High-Energy-Density Shear Layers

    NASA Astrophysics Data System (ADS)

    Flippo, K. A.; Doss, F. W.; Kline, J. L.; Merritt, E. C.; Capelli, D.; Cardenas, T.; DeVolder, B.; Fierro, F.; Huntington, C. M.; Kot, L.; Loomis, E. N.; MacLaren, S. A.; Murphy, T. J.; Nagel, S. R.; Perry, T. S.; Randolph, R. B.; Rivera, G.; Schmidt, D. W.

    2016-11-01

    Using a large volume high-energy-density fluid shear experiment (8.5 cm3 ) at the National Ignition Facility, we have demonstrated for the first time the ability to significantly alter the evolution of a supersonic sheared mixing layer by controlling the initial conditions of that layer. By altering the initial surface roughness of the tracer foil, we demonstrate the ability to transition the shear mixing layer from a highly ordered system of coherent structures to a randomly ordered system with a faster growing mix layer, indicative of strong mixing in the layer at a temperature of several tens of electron volts and at near solid density. Simulations using a turbulent-mix model show good agreement with the experimental results and poor agreement without turbulent mix.

  4. Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

    PubMed Central

    Scheibel, Paula Cabrini; Ramos, Adilson Luiz; Iwaki, Lilian Cristina Vessoni; Micheletti, Kelly Regina

    2014-01-01

    OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI) and external apical root resorption (EARR) after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1) and after 12 months of treatment (T2). ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157). CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction. PMID:25715722

  5. Late-Time Mixing Sensitivity to Initial Broadband Surface Roughness in High-Energy-Density Shear Layers

    SciTech Connect

    Flippo, K. A.; Doss, F. W.; Kline, J. L.; Merritt, E. C.; Capelli, D.; Cardenas, T.; DeVolder, B.; Fierro, F.; Huntington, C. M.; Kot, L.; Loomis, E. N.; MacLaren, S. A.; Murphy, T. J.; Nagel, S. R.; Perry, T. S.; Randolph, R. B.; Rivera, G.; Schmidt, D. W.

    2016-11-23

    Using a large volume high-energy-density fluid shear experiment (8.5 cm3) at the National Ignition Facility, we have demonstrated for the first time the ability to significantly alter the evolution of a supersonic sheared mixing layer by controlling the initial conditions of that layer. By altering the initial surface roughness of the tracer foil, we demonstrate the ability to transition the shear mixing layer from a highly ordered system of coherent structures to a randomly ordered system with a faster growing mix layer, indicative of strong mixing in the layer at a temperature of several tens of electron volts and at near solid density. Simulations using a turbulent-mix model show good agreement with the experimental results and poor agreement without turbulent mix.

  6. Identification of P-glycoprotein co-fractionating proteins and specific binding partners in rat brain microvessels.

    PubMed

    Tome, Margaret E; Schaefer, Charles P; Jacobs, Leigh M; Zhang, Yifeng; Herndon, Joseph M; Matty, Fabian O; Davis, Thomas P

    2015-07-01

    Drug delivery to the brain for the treatment of pathologies with a CNS component is a significant clinical challenge. P-glycoprotein (PgP), a drug efflux pump in the endothelial cell membrane, is a major factor in preventing therapeutics from crossing the blood-brain barrier (BBB). Identifying PgP regulatory mechanisms is key to developing agents to modulate PgP activity. Previously, we found that PgP trafficking was altered concomitant with increased PgP activity and disassembly of high molecular weight PgP-containing complexes during acute peripheral inflammatory pain. These data suggest that PgP activity is post-translationally regulated at the BBB. The goal of the current study was to identify proteins that co-localize with PgP in rat brain microvessel endothelial cell membrane microdomains and use the data to suggest potential regulatory mechanisms. Using new density gradients of microvessel homogenates, we identified two unique pools (1,2) of PgP in membrane fractions. Caveolar constituents, caveolin1, cavin1, and cavin2, co-localized with PgP in these fractions indicating the two pools contained caveolae. A chaperone (Hsc71), protein disulfide isomerase and endosomal/lysosomal sorting proteins (Rab5, Rab11a) also co-fractionated with PgP in the gradients. These data suggest signaling pathways with a potential role in post-translational regulation of PgP activity at the BBB.

  7. Real-time broadening of nonequilibrium density profiles and the role of the specific initial-state realization

    NASA Astrophysics Data System (ADS)

    Steinigeweg, R.; Jin, F.; Schmidtke, D.; De Raedt, H.; Michielsen, K.; Gemmer, J.

    2017-01-01

    The real-time broadening of density profiles starting from nonequilibrium states is at the center of transport in condensed-matter systems and dynamics in ultracold atomic gases. Initial profiles close to equilibrium are expected to evolve according to the linear response, e.g., as given by the current correlator evaluated exactly at equilibrium. Significantly off equilibrium, the linear response is expected to break down and even a description in terms of canonical ensembles is questionable. We unveil that single pure states with density profiles of maximum amplitude yield a broadening in perfect agreement with the linear response, if the structure of these states involves randomness in terms of decoherent off-diagonal density-matrix elements. While these states allow for spin diffusion in the XXZ spin-1 /2 chain at large exchange anisotropies, coherences yield entirely different behavior.

  8. Acoustic response of compliable microvessels containing ultrasound contrast agents.

    PubMed

    Qin, Shengping; Ferrara, Katherine W

    2006-10-21

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 microm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 microm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 microm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the

  9. Acoustic response of compliable microvessels containing ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Qin, Shengping; Ferrara, Katherine W.

    2006-10-01

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 µm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 µm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 µm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the

  10. Influence of initial pesticide concentrations and plant population density on dimethomorph toxicity and removal by two duckweed species.

    PubMed

    Dosnon-Olette, Rachel; Couderchet, Michel; El Arfaoui, Achouak; Sayen, Stéphanie; Eullaffroy, Philippe

    2010-04-15

    Aquatic plants take up, transform and sequester organic contaminants and may therefore be used in phytoremediation for the removal of pollutants from wastewaters. A better understanding of factors affecting the rate of contaminant uptake by aquatic plants is needed to improve engineered systems for removal of pollutants from wastewaters. This work focused on the influence of initial concentrations of pesticide and population density of plants on toxicity and uptake of the fungicide dimethomorph by two duckweed species. An increased sensitivity to dimethomorph was observed with increasing duckweed population density. Less light, due to crowding, may explain this higher sensitivity and reduced removal rate. A positive relationship was also found between toxicity or contaminant uptake and initial pesticide concentration with a maximal removal of 41 and 26 microg g(-1) fresh weight of dimethomorph (at 600 microg L(-1) of dimethomorph and an initial density of 0.10g E-flask(-1)) by Lemna minor and Spirodela polyrhiza, respectively. This research also indicated that these aquatic plants can efficiently eliminate organic contaminants and may ultimately serve as phytoremediation agents in the natural environment. Copyright 2010 Elsevier B.V. All rights reserved.

  11. ELUCID - Exploring the Local Universe with ReConstructed Initial Density Field III: Constrained Simulation in the SDSS Volume

    NASA Astrophysics Data System (ADS)

    Wang, Huiyuan; Mo, H. J.; Yang, Xiaohu; Zhang, Youcai; Shi, JingJing; Jing, Y. P.; Liu, Chengze; Li, Shijie; Kang, Xi; Gao, Yang

    2016-11-01

    A method we developed recently for the reconstruction of the initial density field in the nearby universe is applied to the Sloan Digital Sky Survey Data Release 7. A high-resolution N-body constrained simulation (CS) of the reconstructed initial conditions, with 30723 particles evolved in a 500 {h}-1 {Mpc} box, is carried out and analyzed in terms of the statistical properties of the final density field and its relation with the distribution of Sloan Digital Sky Survey galaxies. We find that the statistical properties of the cosmic web and the halo populations are accurately reproduced in the CS. The galaxy density field is strongly correlated with the CS density field, with a bias that depends on both galaxy luminosity and color. Our further investigations show that the CS provides robust quantities describing the environments within which the observed galaxies and galaxy systems reside. Cosmic variance is greatly reduced in the CS so that the statistical uncertainties can be controlled effectively, even for samples of small volumes.

  12. Assessment of bone density in the posterior maxilla based on Hounsfield units to enhance the initial stability of implants.

    PubMed

    Sogo, Motofumi; Ikebe, Kazunori; Yang, Tsung-Chieh; Wada, Masahiro; Maeda, Yoshinobu

    2012-05-01

    The poor bone quality that exists in the posterior maxilla is associated with lower initial stability and higher failure rates in implants. This study examined the bone densities of edentulous posterior maxillae by computed tomography (CT). Based on CT images, the voxel values representing implant replacement in the posterior maxillary regions of 30 patients were calculated in the range from 150 to 2,000 Hounsfield units (HU). The bone densities of these regions were categorized according to Misch's classification and compared among individuals and between sexes. The average of the median individual CT values was 495 HU (95% confidence interval: 442-547 HU) and was significantly higher in males than in females. Most of the bone in the posterior maxillae was classified as D3 (350-850 HU) or D4 (150-350 HU) according to Misch's classification, comprising 50% and 32% of the entire regions, respectively. More than 80% of the edentulous posterior maxillae consisted of porous cortical crest or no cortical bone according to CT, although the bone densities varied markedly among individuals. More detailed assessments of bone density may be useful to enhance initial stability of implants in the posterior maxilla. © 2011 Wiley Periodicals, Inc.

  13. Measurement of filtration coefficient in single cerebral microvessels of the frog.

    PubMed

    Fraser, P A; Dallas, A D; Davies, S

    1990-04-01

    1. This study reports the first results of measurements of filtration coefficient (Lp) and osmotic reflection coefficient to sucrose (sigma suc) in single brain microvessels. 2. Microvessels on the surface of frog brain were cannulated with a micropipette and perfused with an artificial cerebrospinal fluid (CSF) containing the low molecular weight impermeant dye carboxyfluorescein (MW 376). The superfusing solution was a similar CSF which could be made hypertonic by the addition of 40-125 mmol l-1 sucrose. 3. Vessels were assessed for dye retention using video-intensified microscopy after occlusion with a glass microneedle. Only six vessels out of a total of ninety-five were tight under the experimental conditions used. Those vessels which were tight were occluded while an osmotic load was applied across them. When this load was 50 mosmol l-1 and less, the steady-state dye concentration within the vessel lumen was similar to that predicted assuming the endothelium behaves as a perfect semipermeable membrane, with concentration polarization of solute. 4. The product Lp sigma was estimated in two ways: (i) from the fitted monoexponential function that described the rising dye concentration within the occluded segment, and (ii) from the initial rate of increase in dye concentration. The two values obtained were similar and it was concluded that sigma NaCl = sigma suc = 1, and the best estimate for filtration coefficient Lp = 2.0 x 10(-9) cm (cmH2O s)-1. 5. At the osmotic loads of 100 mosmol l-1 and more, the initial rate of increase estimate of Lp sigma was less than half of the whole curve estimate, the axial dye distributions were dissimilar from those predicted by a mathematical model based on the perfect semipermeable membrane, and the steady-state concentration was less than 70% of that expected. These findings are consistent with a diffusive pathway having opened. The model was modified to include patches of vessel wall which had developed leaks and a good fit

  14. Aligned Human Microvessels Formed in 3D Fibrin Gel by Constraint of Gel Contraction

    PubMed Central

    Morin, Kristen T.; Smith, Annie O.; Davis, George E.; Tranquillo, Robert T.

    2013-01-01

    This study aimed to form microvessels in fibrin gels, which is of interest both for studying the fundamental cell-matrix interactions as well as for tissue engineering purposes, and to align the microvessels, which would provide natural inlet and outlet sides for perfusion. The data reported here demonstrate the formation of highly interconnected microvessels in fibrin gel under defined medium conditions and the ability to align them using two methods, both of which involved anchoring the gel at both ends to constrain the cell-induced compaction. The first method used only defined medium and resulted in moderate alignment. The second method used defined and serum-containing media sequentially to achieve high levels of microvessel alignment. PMID:23938272

  15. Spectral imaging reveals microvessel physiology and function from anastomoses to thromboses

    NASA Astrophysics Data System (ADS)

    Wankhede, Mamta; Agarwal, Nikita; Fraga-Silva, Rodrigo A.; Dedeugd, Casey; Raizada, Mohan K.; Oh, S. Paul; Sorg, Brian S.

    2010-01-01

    Abnormal microvascular physiology and function is common in many diseases. Numerous pathologies include hypervascularity, aberrant angiogenesis, or abnormal vascular remodeling among the characteristic features of the disease, and quantitative imaging and measurement of microvessel function can be important to increase understanding of these diseases. Several optical techniques are useful for direct imaging of microvascular function. Spectral imaging is one such technique that can be used to assess microvascular oxygen transport function with high spatial and temporal resolution in microvessel networks through measurements of hemoglobin saturation. We highlight novel observation made with our intravital microscopy spectral imaging system employed with mouse dorsal skin-fold window chambers for imaging hemoglobin saturation in microvessel networks. Specifically, we image acute oxygenation fluctuations in a tumor microvessel network, the development of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia, and the formation of spontaneous and induced microvascular thromboses and occlusions.

  16. Initiation of conidiation in Erysiphe necator is regulated by prior vegetative growth, inoculum density and light

    USDA-ARS?s Scientific Manuscript database

    Initiation of asexual sporulation in powdery mildews is preceded by a period of superficial vegetative growth of mildew colonies. We found evidence of signaling in Erysiphe necator that was promulgated at the colony center as early as five days after inoculation and stimulated sporulation throughout...

  17. Plant Response to Soils, Site Preparation, and Initial Pine Planting Density

    Treesearch

    Henry A. Pearson; Gale L. Wolters; Ronald E. Thill; Alton Martin; V. Clark Baldwin

    1995-01-01

    This study described the effects of soils, site preparation, and initial pine regeneration spacings on tree growth and the associated understory woody and herbaceous plant succession. Although Sawyer soils appeared more productive than Ruston soils before the harvest and regeneration treatments, woody and herbaceous plant differences were not apparent between the...

  18. Trait- and density-mediated indirect interactions initiated by an exotic invasive plant autogenic ecosystem engineer

    Treesearch

    Dean E. Pearson

    2010-01-01

    Indirect interactions are important for structuring ecological systems. However, research on indirect effects has been heavily biased toward top-down trophic interactions, and less is known about other indirect-interaction pathways. As autogenic ecosystem engineers, plants can serve as initiators of nontrophic indirect interactions that, like top-down pathways, can...

  19. An experimental investigation of the dynamics of submarine leveed channel initiation as sediment-laden density currents experience sudden unconfinement

    SciTech Connect

    Rowland, Joel C; Hilley, George E; Fildani, Andrea

    2009-01-01

    Leveed submarine channels play a critical role in the transfer of sediment from the upper continental slopes to interslope basins and ultimately deepwater settings. Despite a reasonable understanding of how these channels grow once established, how such channels initiate on previously unchannelized portions of the seafloor remains poorly understood. We conducted a series of experiments that elucidate the influence of excess density relative to flow velocity on the dynamics of, and depositional morphologies arising from, density currents undergoing sudden unconfinement across a sloped bed. Experimental currents transported only suspended sediment across a non-erodible substrate. Under flow conditions ranging from supercritical to subcritical (bulk Richardson numbers of 0.02 to 1.2) our experiments failed to produce deposits resembling or exhibiting the potential to evolve into self-formed leveed channels. In the absence of excess density, a submerged sediment-laden flow produced sharp crested lateral deposits bounding the margins of the flow for approximately a distance of two outlet widths down basin. These lateral deposits terminated in a centerline deposit that greatly exceeded marginal deposits in thickness. As excess density increased relative to the outlet velocity, the rate of lateral spreading of the flow increased relative to the downstream propagation of the density current, transitioning from a narrow flow aligned with the channel outlet to a broad radially expanding flow. Coincident with these changes in flow dynamics, the bounding lateral deposits extended for shorter distances, had lower, more poorly defined crests that were increasingly wider in separation than the initial outlet, and progressively became more oblong rather than linear. Based on our results, we conclude that leveed channels cannot initiate from sediment-laden density currents under strictly depositional conditions. Partial confinement of these currents appears to be necessary to

  20. Hydrodynamic behavior of tumor cells in a confined model microvessel

    NASA Astrophysics Data System (ADS)

    Khan, Zeina S.; Vanapalli, Siva A.

    2012-02-01

    An important step in cancer metastasis is the hydrodynamic transport of circulating tumor cells (CTCs) through microvasculature. In vivo imaging studies in mice models show episodes of confined motion and trapping of tumor cells at microvessel bifurcations, suggesting that hydrodynamic phenomena are important processes regulating CTC dissemination. Our goal is to use microfluidics to understand the interplay between tumor cell rheology, confinement and fluid forces that may help to identify physical factors determining CTC transport. We use leukemia cells as model CTCs and mimic the in vivo setting by investigating their motion in a confined microchannel with an integrated microfluidic manometer to measure time variations in the excess pressure drop during cell motion. Using image analysis, variations in excess pressure drop, cell shape and cell velocity are simultaneously quantified. We find that the throughput of the technique is high enough ( 100 cells/min) to assess tumor cell heterogeneity. Therefore, in addition to measuring the hydrodynamic response of tumor cells in confined channels, our results indicate that the microfluidic manometer device could be used for rapid mechanical phenotyping of tumor cells.

  1. Neutral amino acid transport across brain microvessel endothelial cell monolayers

    SciTech Connect

    Audus, K.L.; Borchardt, R.T.

    1986-03-01

    Brain microvessel endothelial cells (BMEC) which form the blood-brain barrier (BBB) possess an amino acid carrier specific for large neutral amino acids (LNAA). The carrier is important for facilitating the delivery of nutrient LNAA's and centrally acting drugs that are LNAA's, to the brain. Bovine BMEC's were isolated and grown up to complete monolayers on regenerated cellulose-membranes in primary culture. To study the transendothelial transport of leucine, the monolayers were placed in a side-by-side diffusion cell, and transport across the monolayers followed with (/sup 3/H)-leucine. The transendothelial transport of leucine in this in vitro model was determined to be bidirectional, and time-, temperature-, and concentration-dependent. The transport of leucine was saturable and the apparent K/sub m/ and V/sub max/, 0.18 mM and 6.3 nmol/mg/min, respectively. Other LNAA's, including the centrally acting drugs, ..cap alpha..-methyldopa, L-DOPA, ..cap alpha..-methyl-tyrosine, and baclofen, inhibited leucine transport. The leucine carrier was also found to be stereospecific and not sensitive to inhibitors of active transport. These results are consistent with previous in vitro and in vivo studies. Primary cultures of BMEC's appear to be a potentially important tool for investigating at the cellular level, the transport mechanisms of the BBB.

  2. Flow of Red Blood Cells in Stenosed Microvessels

    PubMed Central

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2016-01-01

    A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis. PMID:27319318

  3. Flow of Red Blood Cells in Stenosed Microvessels

    NASA Astrophysics Data System (ADS)

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2016-06-01

    A computational study is presented on the flow of deformable red blood cells in stenosed microvessels. It is observed that the Fahraeus-Lindqvist effect is significantly enhanced due to the presence of a stenosis. The apparent viscosity of blood is observed to increase by several folds when compared to non-stenosed vessels. An asymmetric distribution of the red blood cells, caused by geometric focusing in stenosed vessels, is observed to play a major role in the enhancement. The asymmetry in cell distribution also results in an asymmetry in average velocity and wall shear stress along the length of the stenosis. The discrete motion of the cells causes large time-dependent fluctuations in flow properties. The root-mean-square of flow rate fluctuations could be an order of magnitude higher than that in non-stenosed vessels. Several folds increase in Eulerian velocity fluctuation is also observed in the vicinity of the stenosis. Surprisingly, a transient flow reversal is observed upstream a stenosis but not downstream. The asymmetry and fluctuations in flow quantities and the flow reversal would not occur in absence of the cells. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis.

  4. Strain energy density-distance criterion for the initiation of stress corrosion cracking of alloy X-750

    SciTech Connect

    Hall, M.M. Jr.; Symons, D.M.

    1996-05-01

    A strain energy density-distance criterion was previously developed and used to correlate rising-load K{sub c} initiation data for notched and fatigue precracked specimens of hydrogen precharged Alloy X-750. This criterion, which was developed for hydrogen embrittlement (HE) cracking, is used here to correlate static-load stress corrosion cracking (SCC) initiation times obtained for smooth geometry, notched and fatigue precracked specimens. The onset of SCC crack growth is hypothesized to occur when a critical strain, which is due to environment-enhanced creep, is attained within the specimen interior. For notched and precracked specimens, initiation is shown by analysis to occur at a variable distance from notch and crack tips. The initiation site varies from very near the crack tip, for highly loaded sharp cracks, to a site that is one grain diameter from the notch, for lower loaded, blunt notches. The existence of hydrogen gradients, which are due to strain-induced hydrogen trapping in the strain fields of notch and crack tips, is argued to be controlling the site for initiation of cracking. By considering the sources of the hydrogen, these observations are shown to be consistent with those from the previous HE study, in which the characteristic distance for crack initiation was found to be one grain diameter from the notch tip, independent of notch radius, applied stress intensity factor and hydrogen level.

  5. Magnetic-nanoparticle-decorated polypyrrole microvessels: toward encapsulation of mRNA cap analogues.

    PubMed

    Kijewska, Krystyna; Jarzębińska, Anita; Kowalska, Joanna; Jemielity, Jacek; Kępińska, Daria; Szczytko, Jacek; Pisarek, Marcin; Wiktorska, Katarzyna; Stolarski, Jarosław; Krysiński, Paweł; Twardowski, Andrzej; Mazur, Maciej

    2013-06-10

    Many phosphorylated nucleoside derivatives have therapeutic potential, but their application is limited by problems with membrane permeability and with intracellular delivery. Here, we prepared polypyrrole microvessel structures modified with superparamagnetic nanoparticles for use as potential carriers of nucleotides. The microvessels were prepared via the photochemical polymerization of the monomer onto the surface of aqueous ferrofluidic droplets. A complementary physicochemical analysis revealed that a fraction of the nanoparticles was embedded in the microvessel walls, while the other nanoparticles were in the core of the vessel. SQUID (superconducting quantum interference device) measurements indicated that the incorporated nanoparticles retained their superparamagnetic properties; thus, the resulting nanoparticle-modified microvessels can be directed by an external magnetic field. As a result of these features, these microvessels may be useful as drug carriers in biomedical applications. To demonstrate the encapsulation of drug molecules, two labeled mRNA cap analogues, nucleotide-derived potential anticancer agents, were used. It was shown that the cap analogues are located in the aqueous core of the microvessels and can be released to the external solution by spontaneous permeation through the polymer walls. Mass spectrometry analysis confirmed that the cap analogues were preserved during encapsulation, storage, and release. This finding provides a foundation for the future development of anticancer therapies and for the delivery of nucleotide-based therapeutics.

  6. Current Fluctuations in One Dimensional Diffusive Systems with a Step Initial Density Profile

    NASA Astrophysics Data System (ADS)

    Derrida, Bernard; Gerschenfeld, Antoine

    2009-12-01

    We show how to apply the macroscopic fluctuation theory (MFT) of Bertini, De Sole, Gabrielli, Jona-Lasinio, and Landim to study the current fluctuations of diffusive systems with a step initial condition. We argue that one has to distinguish between two ways of averaging (the annealed and the quenched cases) depending on whether we let the initial condition fluctuate or not. Although the initial condition is not a steady state, the distribution of the current satisfies a symmetry very reminiscent of the fluctuation theorem. We show how the equations of the MFT can be solved in the case of non-interacting particles. The symmetry of these equations can be used to deduce the distribution of the current for several other models, from its knowledge (Derrida and Gerschenfeld in J. Stat. Phys. 136, 1-15, 2009) for the symmetric simple exclusion process. In the range where the integrated current Qt˜sqrt{t} , we show that the non-Gaussian decay exp [- Q {/t 3}/ t] of the distribution of Q t is generic.

  7. Bisphosphonates' antiangiogenic potency in the development of bisphosphonate-associated osteonecrosis of the jaws: influence on microvessel sprouting in an in vivo 3D Matrigel assay.

    PubMed

    Pabst, A M; Ziebart, T; Ackermann, M; Konerding, M A; Walter, C

    2014-04-01

    Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is an adverse side effect of long-term bisphosphonate treatment. One theory of BP-ONJ etiology suggests a negative influence of these agents on angiogenesis and vascularization. This in vivo study analyzed the effects of bisphosphonates on angiogenesis in a 3D Matrigel assay. Matrigel plugs were implanted into fifty 6-8-week-old female nude mice. Ten animals each were treated either with clodronate, ibandronate, pamidronate, zoledronate, or carrier solution as controls. The microvessel density (MVD), microvessel area (MVA), and microvessel size (MVS) in Matrigel plugs were analyzed after 21 days of treatment by immunohistochemistry and exemplary 3D microvascular corrosion castings. All bisphosphonates induced a statistically significant decrease of MVD (p each <0.001), whereby the nitrogen-containing bisphosphonates (N-BPs) demonstrated a clearly stronger effect than non-nitrogen-containing bisphosphonates (NN-BP) clodronate (control 166, clodronate 99, ibandronate 48, pamidronate 47, zoledronate 35 microvessels/mm(2)). Referring to MVA, similar results could be detected. MVS was significantly increased especially by ibandronate (103 %) compared to control group (p < 0.001). Scanning electron microscope scans of the corrosion castings confirmed these results. The stronger influence on MVD by N-BPs compared to the NN-BP clodronate may explain for the lack of BP-ONJ after treatment with NN-BPs. Ibandronate induced a strong increase of MVS. In combination with the reduced MVD, this could result only in a fractional reduced perfusion which might be an explanation for the lower occurrence of BP-ONJ in patients receiving ibandronate compared to patients receiving pamidronate or zoledronate.

  8. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  9. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Huls, M. H.; Sams, C. F.

    1991-01-01

    Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.

  10. Temperature and initial curvature effects in low-density panel flutter

    NASA Technical Reports Server (NTRS)

    Resende, Hugo B.

    1992-01-01

    The panel flutter phenomenon is studied assuming free-molecule flow. This kind of analysis is relevant in the case of hypersonic flight vehicles traveling at high altitudes, especially in the leeward portion of the vehicle. In these conditions the aerodynamic shear can be expected to be considerably larger than the pressure at a given point, so that the effects of such a loading are incorporated into the structural model. Both the pressure and shear loadings are functions of the panel temperature, which can lead to great variations on the location of the stability boundaries for parametric studies. Different locations can, however, be 'collapsed' onto one another by using as ordinate an appropriately normalized dynamic pressure parameter. This procedure works better for higher values of the panel temperature for a fixed undisturbed flow temperature. Finally, the behavior of the system is studied when the panel has some initial curvature. This leads to the conclusion that it may be unrealistic to try to distinguish between a parabolic or sinusoidal initial shape.

  11. Strain energy density: Distance criterion for the initiation of hydrogen-induced cracking of Alloy X-750

    SciTech Connect

    Hall, M.M. Jr.; Symons, D.M.; Kearns, J.J.

    1991-12-31

    A criterion for initiation of subcritical crack growth at blunt notches and sharp defects was developed and applied to hydrogen- induced cracking of the Ni-base superalloy X-750. Onset of crack growth is shown to occur when a critical strain energy density is attained at a distance from the notch and crack tips characteristic of the microstructure along the prospective crack path. Rising load crack growth initiation data were obtained using homogeneous hydrogen precharged notched and fatigue precracked bend specimens. Notch root radius, grain size and hydrogen concentration were varied. Crack growth initiation loads were dependent on both notch root radius and bulk precharged hydrogen concentration. These data were shown to be correlated using a critical strain energy at-a-distance (SEDAD) criterion. Furthermore, an elastic-plastic analysis of the strain energy distributions showed that the critical strain energy density value is attained at one grain diameter from the notch and fatigue precrack tips. Mechanical and microstructural aspects of crack growth process and relevance to hydrogen-induced cracking are discussed.

  12. Targeted disruption of deep-lying neocortical microvessels in rat using ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Nishimura, Nozomi; Schaffer, Christopher B.; Friedman, Beth; Tsai, Philbert S.; Lyden, Patrick D.; Kleinfeld, David

    2004-06-01

    The study of neurovascular diseases such as vascular dementia and stroke require novel models of targeted vascular disruption in the brain. We describe a model of microvascular disruption in rat neocortex that uses ultrashort laser pulses to induce localized injury to specific targeted microvessels and uses two-photon microscopy to monitor and guide the photodisruption process. In our method, a train of high-intensity, 100-fs laser pulses is tightly focused into the lumen of a blood vessel within the upper 500 μm of cortex. Photodisruption induced by these laser pulses creates injury to a single vessel located at the focus of the laser, leaving the surrounding tissue intact. This photodisruption results in three modalities of localized vascular injury. At low power, blood plasma extravasation can be induced. The vessel itself remains intact, while serum is extravasated into the intercellular space. Localized ischemia caused by an intravascular clot results when the photodisruption leads to a brief disturbance of the vascular walls that initiates an endogenous clotting cascade. The formation of a localized thrombus stops the blood flow at the location of the photodisruption. A hemorrhage, defined as a large extravasation of blood including plasma and red blood cells, results when higher laser power is used. The targeted vessel does not remain intact.

  13. A comparison of the kinetics of low-density lipoprotein oxidation initiated by copper or by azobis (2-amidinopropane).

    PubMed

    Thomas, M J; Chen, Q; Franklin, C; Rudel, L L

    1997-01-01

    This article describes the kinetics of low density lipoprotein (LDL) oxidation catalyzed by azobis (2-amidinopropane) dihydrochloride, ABAP, or by copper. The LDLs were isolated from nonhuman primates fed diets enriched in one of three types of fatty acids: saturated fatty acids, monounsaturated fatty acids, predominantly, oleic acid, or polyunsaturated fatty acids, predominantly linoleic acid. Oxidation was followed by monitoring the formation of conjugated diene hydroperoxides from polyunsaturated fatty acids (PUFA). For both copper and ABAP-initiated oxidation, the rate of LDL oxidation depended on the concentrations of initiator, PUFA, and LDL. Except for the dependence on PUFA concentration the rate of LDL oxidation was not directly influenced by the fatty acid composition of the LDL particle. The two initiators had very different dependence on initiator concentration. Because LDL particles are essentially small, lipid-rich droplets, the kinetic descriptions of LDL oxidation assumed: (1), that there was only one chain per particle, and (2) that the radical chain was terminated when a second radical either entered or was formed in the particle. When two LDL samples having very different lag times were mixed, the oxidation profile was bimodal. This finding demonstrated that the oxidation of native LDL particles was independent of the oxidation state of the other native LDL particles in solution, i.e., LDL particles do not rapidly exchange radicals, for example, hydroperoxyl radicals. Oxidation initiated by ABAP was proportional to [ABAP]0.5, suggesting that hydroperoxyl radical recombination between the lipid hydroperoxyl radical and the ABAP-hydroperoxyl radical was the chain-terminating step. The reciprocal of the rate of copper oxidation was linearly related to the reciprocal copper concentration, demonstrating that the binding of copper to LDL was necessary to initiate oxidation. This binding constant showed considerable variability among LDL samples. The

  14. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy.

    PubMed

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M

    2010-03-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.

  15. Estimation of Distribution Algorithm for Initial Orbit Determination of Too-short-arc Based on Kernel Density Estimation

    NASA Astrophysics Data System (ADS)

    Wang, X.; Li, X. R.

    2016-11-01

    A new approach of the initial orbit determination for too-short-arc with angular measurements is implemented by building the probabilistic model in the solution space with the estimation of distribution algorithm. Without any assumption of distribution, the non-parametric kernel density estimation is employed in the model building. The method, unlike other evolutionary algorithms, such as genetic algorithm and particle swarm optimization, considers the fitness as well as the characteristic of solution space. Numerical check with real observations indicates that without any constraints, the proposed technique has a good performance for the measurements of general accuracy.

  16. Initial oxidation of gallium arsenide (001)-β2(2 x 4) surface using density functional theory.

    PubMed

    Kim, Dae-Hee; Kim, Dae-Hyun; Kim, Yeong-Cheol

    2014-10-01

    The initial oxidation of a gallium arsenide (001)-β2(2 x 4) surface with an oxygen molecule was investigated using density functional theory. The oxygen molecule was adsorbed on the surface without any energy barrier. The dissociation of the oxygen molecule on the first arsenic layer had two dissociation paths; the inter-dimer and intra-dimer. The inter-dimer dissociation was the dominant dissociation path based on the energy barriers. The two dissociated oxygen atoms preferred breaking the arsenic-gallium back-bond to form arsenic-oxygen-gallium bonds. Our results are in good agreement with literature of the scanning tunneling microscope study.

  17. High-Density Transcriptional Initiation Signals Underline Genomic Islands in Bacteria

    PubMed Central

    Huang, Qianli; Cheng, Xuanjin; Cheung, Man Kit; Kiselev, Sergey S.; Ozoline, Olga N.; Kwan, Hoi Shan

    2012-01-01

    Genomic islands (GIs), frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of “alien” elements which probably undergo special temporal–spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these “exotic” regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs) in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased “non-optimal” codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for “alien” regions, but also provide hints to the special

  18. Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay.

    PubMed

    Caviglia, C; Zór, K; Canepa, S; Carminati, M; Larsen, L B; Raiteri, R; Andresen, T L; Heiskanen, A; Emnéus, J

    2015-05-21

    We investigated the combined effect of the initial cell density (12,500, 35,000, 75,000, and 100,000 cells cm(-2)) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing time-dependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell-substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 μM doxorubicin, whereas the impedance showed at this time point cell viability that was below 25%. These results indicate that impedance detection reveals cytotoxic events undetectable when using the MTS assay, highlighting the importance of combining impedance detection with traditional drug toxicity assays towards a more in depth understanding of the effect of anti-cancer drugs on in vitro assays. Moreover, the detection of doxorubicin induced toxicity determined with impedance under static conditions proved to be 6 times faster than in perfusion culture.

  19. A comparison of the effects of initializing different thermosphere-ionosphere model fields on storm time plasma density forecasts

    NASA Astrophysics Data System (ADS)

    Chartier, Alex T.; Jackson, David R.; Mitchell, Cathryn N.

    2013-11-01

    assimilation has been used successfully for real-time ionospheric specification, but it has not yet proved advantageous for forecasting. The most challenging and important ionospheric events to forecast are storms. The work presented here examines the effectiveness of data assimilation in a storm situation, where the initial conditions are known and the model is considered to be correct but the external solar and geomagnetic drivers are poorly specified. The aim is to determine whether data assimilation could be used to improve storm time forecast accuracy. The results show that, in the case of the storm of Halloween 2003, changes made to the model's initial thermospheric conditions improve electron density forecasts by at least 10% for 18 h, while changes to ionospheric fields alone result in >10% forecast accuracy improvement for less than 4 h. Further examination shows that the neutral composition is especially important to the accuracy of ionospheric electron density forecasts. Updating the neutral composition gives almost all the benefits of updating the complete thermospheric state. A comparison with real, globally distributed observations of vertical total electron content confirms that updating the thermospheric composition can improve forecast accuracy.

  20. Miscible gravitational instability of initially stable horizontal interface in a porous medium: Non-monotonic density profiles

    NASA Astrophysics Data System (ADS)

    Kim, Min Chan

    2014-11-01

    To simulate a CO2 sequestration process, some researchers employed a water/propylene glycol (PPG) system which shows a non-monotonic density profile. Motivated by this fact, the stability of the diffusion layer of two miscible fluids saturated in a porous medium is analyzed. For a non-monotonic density profile system, linear stability equations are derived in a global domain, and then transformed into a system of ordinary differential equations in an infinite domain. Initial growth rate analysis is conducted without the quasi-steady state approximation (QSSA) and shows that initially the system is unconditionally stable for the least stable disturbance. For the time evolving case, the ordinary differential equations are solved applying the eigen-analysis and numerical shooting scheme with and without the QSSA. To support these theoretical results, direct numerical simulations are conducted using the Fourier spectral method. The results of theoretical linear stability analyses and numerical simulations validate one another. The present linear and nonlinear analyses show that the water/PPG system is more unstable than the CO2/brine one, and the flow characteristics of these two systems are quite different from each other.

  1. Flow of a circulating tumor cell and red blood cells in microvessels

    NASA Astrophysics Data System (ADS)

    Takeishi, Naoki; Imai, Yohsuke; Yamaguchi, Takami; Ishikawa, Takuji

    2015-12-01

    Quantifying the behavior of circulating tumor cells (CTCs) in the blood stream is of fundamental importance for understanding metastasis. Here, we investigate the flow mode and velocity of CTCs interacting with red blood cells (RBCs) in various sized microvessels. The flow of leukocytes in microvessels has been described previously; a leukocyte forms a train with RBCs in small microvessels and exhibits margination in large microvessels. Important differences in the physical properties of leukocytes and CTCs result from size. The dimensions of leukocytes are similar to those of RBCs, but CTCs are significantly larger. We investigate numerically the size effects on the flow mode and the cell velocity, and we identify similarities and differences between leukocytes and CTCs. We find that a transition from train formation to margination occurs when (R -a ) /tR≈1 , where R is the vessel radius, a is the cell radius, and tR is the thickness of RBCs, but that the motion of RBCs differs from the case of leukocytes. Our results also show that the velocities of CTCs and leukocytes are larger than the average blood velocity, but only CTCs move faster than RBCs for microvessels of R /a ≈1.5 -2.0 . These findings are expected to be useful not only for understanding metastasis, but also for developing microfluidic devices.

  2. Cathepsin L acutely alters microvessel integrity within the neurovascular unit during focal cerebral ischemia

    PubMed Central

    Gu, Yu-Huan; Kanazawa, Masato; Hung, Stephanie Y; Wang, Xiaoyun; Fukuda, Shunichi; Koziol, James A; del Zoppo, Gregory J

    2015-01-01

    During focal cerebral ischemia, the degradation of microvessel basal lamina matrix occurs acutely and is associated with edema formation and microhemorrhage. These events have been attributed to matrix metalloproteinases (MMPs). However, both known protease generation and ligand specificities suggest other participants. Using cerebral tissues from a non-human primate focal ischemia model and primary murine brain endothelial cells, astrocytes, and microglia in culture, the effects of active cathepsin L have been defined. Within 2 hours of ischemia onset cathepsin L, but not cathepsin B, activity appears in the ischemic core, around microvessels, within regions of neuron injury and cathepsin L expression. In in vitro studies, cathepsin L activity is generated during experimental ischemia in microglia, but not astrocytes or endothelial cells. In the acidic ischemic core, cathepsin L release is significantly increased with time. A novel ex vivo assay showed that cathepsin L released from microglia during ischemia degrades microvessel matrix, and interacts with MMP activity. Hence, the loss of microvessel matrix during ischemia is explained by microglial cathepsin L release in the acidic core during injury evolution. The roles of cathepsin L and its interactions with specific MMP activities during ischemia are relevant to strategies to reduce microvessel injury and hemorrhage. PMID:26198177

  3. Visualization of Microvessels in Skin by Three-Dimensional Ultrasound Microscope

    NASA Astrophysics Data System (ADS)

    Saijo, Y.; Kobayashi, K.; Hozumi, N.; Tanaka, A.; Sakai, S.

    A non-invasive imaging technique capable of visualizing microvessels through epidermis to subdermis has been strongly desired. A PVDF ultrasonic transducer with the central frequency of 100 MHz and the focal length of 3.2 mm was mechanically scanned over the objects by two linear servo motors controlled by a personal computer. A microvessel model was made of a tungsten wire with a diameter of 100-microns and placed in the water tank. The microvessel model was clearly visualized by 3D ultrasound microscope. In cases of skin imaging, conventional echo gel was used as the coupling medium between transducer and skin surface. In vivo 3D skin morphology was also clearly visualized. In dermis, a microvessel may be shown as small, round, lucent echo areas continuously observed in the serial sections. 3D structure of hair-follicle was also visualized from the skin surface to the bud of hair-follicle in dermis. The 3D ultrasound microscope noninvasively provides important information on the distribution of microvessels in skin.

  4. Shear stress variation induced by red blood cell motion in microvessel.

    PubMed

    Xiong, Wenjuan; Zhang, Junfeng

    2010-08-01

    We simulated red blood cells flowing in microvessel to examine the induced wall shear stress variation. A typical peak-valley-peak structure is observed, and it is analyzed in terms of its magnitude, spatial influencing range, and temporal elapsed duration. Effects of red cell deformability, microvessel size, and flow velocity have been investigated. The corresponding variation characters have also been related to cell deformation and flow field. Simulation results show that the variation magnitude is mainly determined by the gap size between cell and vessel wall, while the spatial range of the shear stress variation depends on the cell length as well as the microvessel size. For a certain point on the vessel wall, the shear stress variation lasts a short time at a higher flow velocity, and vice versa. As the cell concentration in the microvessel increases, the shear stress variation structure changes accordingly with the two peaks from two close cells merging together, and eventually only one peak is observed at a hematocrit of 30.72%. However, the effect of hematocrit on the variation magnitude of shear stress is less obvious, and the dynamic nature of shear stress is still significant. This represents the first attempt to study the dynamic shear stress variation on microvessel as red blood cells flow by, and the information obtained in this study could be valuable to relevant research, for example, the mechanotransduction in the endothelia glycocalyx layer.

  5. Shock associated with endothelial dysfunction in omental microvessels.

    PubMed

    Somberg, Lewis B; Gutterman, David D; Miura, Hiroto; Nirula, Raminder; Hatoum, Ossama A

    2017-01-01

    Impaired microvascular function leads to a poor outcome in a variety of medical conditions. Our aim was to determine whether vasodilator responses to acetylcholine (Ach) are impaired in human omental arterioles from patients with severe trauma. Patients with massive blood loss and severe shock requiring damage control procedures were included. Tissues were collected at the first (FEL) and the second explorative laparotomy (SEL). Control tissues were collected from nontrauma patients. Freshly isolated 50-200-μm-diameter omental arterioles were analysed using videomicroscopy. Dihydroethidine and DCF-DA fluorescence were used to assess reactive oxygen species (ROS) production. MnTBAP was used to determine the contribution of excess vascular superoxide contribution to endothelial dysfunction. After constriction (30-50%) with endothelin-1, dilation to graded doses of Ach (10(-9) -10(-4) M) was greater in control vessels compared to FEL and SEL (max dilation at 10(-4) M (MD) = 25 ± 3%, n = 8; and 59 ± 8%, n = 8, respectively, and controls MD = 93 ± 10%, n = 6, P < 0·05). Fluorescence imaging of ROS production showed significant increases in superoxide (225·46 ± 12·86; 215·77 ± 10·75 vs. 133·75 ± 7·26, arbitrary units; P < 0·05) and peroxide-related ROS (240·8 ± 20·42; 234·59 ± 28·86, vs. 150·78 ± 15·65, arbitrary units; P < 0·05), in FEL and SEL microvessels compared to control, respectively. FEL pretreated with MnTBAP demonstrated significant improvement in Ach-induced vasodilation (25·5 ± 3·0% vs. 79·5 ± 8·2%; P < 0·05). Severe shock associated with microvascular endothelial dysfunction enhances production of ROS in human omental tissues. The altered flow regulation may contribute to a mismatch between local blood supply and demand, exacerbating abnormal tissue perfusion and function. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  6. Acoustic response of compliable microvessels containing ultrasound contrast agents

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2010-01-01

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble’s oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than UCA size. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA’s oscillation and the microvessel’s acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 micron vessel with a peak negative pressure of 0.1MPa and a center frequency of 1MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with the range of diameters considered in this work, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless the vessel diameter, however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a center frequency of 1MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 μm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease, however the

  7. LIPUS promotes spinal fusion coupling proliferation of type H microvessels in bone

    PubMed Central

    Xu, Ximing; Wang, Fei; Yang, Yahong; Zhou, Xiaoyi; Cheng, Yajun; Wei, Xianzhao; Li, Ming

    2016-01-01

    Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate spinal fusion. Type H microvessels are found in close relation with bone development. We analyzed the role of type H vessels in rat spinal fusion model intervened by LIPUS. It was found LIPUS could significantly accelerate bone fusion rate and enlarge bone callus. Osteoblasts were specifically located on the bone meshwork of the allograft, and were surrounded by type H microvessels. LIPUS could significantly increase the quantity of osteoblasts during spine fusion, which process was coupled with elevated angiogenesis of type H microvessels. Our results suggest that LIPUS may be a noninvasive adjuvant treatment modality in spinal fusion for clinical use. The treatment is recommended for usage for at least one month. PMID:26830666

  8. Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation

    PubMed Central

    Grant, Philip M.; Kitch, Douglas; McComsey, Grace A.; Dube, Michael P.; Haubrich, Richard; Huang, Jeannie; Riddler, Sharon; Tebas, Pablo; Zolopa, Andrew R.; Collier, Ann C.; Brown, Todd T.

    2013-01-01

    Background. Bone mineral density (BMD) decreases 2%–6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. Methods. We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4+ and 16-week CD4+ change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)– or tenofovir-containing regimen on 96-week total BMD change. Results. The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4+ cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4+ <50 cells/µL lost significantly more BMD compared to those with CD4+ ≥500 cells/µL. A greater relative, but not absolute, 16-week increase in CD4+ count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4+ count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. Conclusions. Low pretreatment CD4+ count, but not greater CD4+ count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4+ counts may reduce the burden of osteoporosis and fragility fractures. PMID:23943825

  9. Alpha-Adrenergic receptors in cerebral microvessels of normotensive and spontaneously hypertensive rats

    SciTech Connect

    Kobayashi, H.; Wada, A.; Izumi, F.; Magnoni, M.S.; Trabucchi, M.

    1985-03-01

    In rat cerebral microvessels, we characterized alpha 1- and alpha 2-adrenergic receptors, using (/sup 3/H)prazosin and (/sup 3/H)-p-amino-clonidine as radioligands. (/sup 3/H)Prazosin binding to the cerebral microvessels was saturable and of high affinity (dissociation constant of 78 pM), with a maximum binding of 48 fmol/mg protein. (/sup 3/H)Prazosin binding reached equilibrium within 15 minutes and was dissociated by the addition of 10 microM phentolamine. The inhibitory effects of isomers of norepinephrine and epinephrine on the binding showed that l-isomers were over 10 times more potent than d-isomers. (/sup 3/H)-p-Amino-clonidine binding to the cerebral microvessels was saturable and of high affinity (K/sub D/ . 0.61 nM) with a B/sub max/ of 73 fmol/mg protein. The binding reached equilibrium within 30 minutes, and was dissociated by the addition of 100 microM l-norepinephrine. l-Isomers of norepinephrine and epinephrine were over 10 times more potent than d-isomers in displacing the binding. Thus, both (/sup 3/H)prazosin and (/sup 3/H)-p-amino-clonidine bindings to the cerebral microvessels were characterized by saturability, high affinity, reversibility, and stereo-specificity. Furthermore, the specificity of both binding sites was pharmacologically evaluated by the inhibitory effects of various adrenergic agonists and antagonists on the bindings. These data indicate the existence of alpha-adrenergic receptors in the cerebral microvessels and are consistent with the hypothesis that the cerebral microcirculation is regulated by adrenergic innervation. Furthermore, the receptors were measured in cerebral microvessels of spontaneously hypertensive rats and Wistar-Kyoto controls.

  10. Dependence of optimal initial density on laser parameters for multi-keV x-ray radiators generated by nanosecond laser-produced underdense plasma

    SciTech Connect

    Tu, Shao-yong; Yuan, Yong-teng; Miao, Wen-yong; Jiang, Shao-en; Ding, Yong-kun; Hu, Guang-yue Zhao, Bin; Zheng, Jian

    2016-01-15

    Efficient multi-keV x-ray sources can be produced using nanosecond laser pulse-heated middle-Z underdense plasmas generated using gas or foam. Previous experimental results show that an optimal initial target density exists for efficient multi-keV x-ray emission at which the laser ionization wave is supersonic. Here we explore the influence of the laser intensity and the pulse duration on this optimal initial target density via a one-dimensional radiation hydrodynamic simulation. The simulation shows that the optimal initial density is sensitive to both the laser intensity and the pulse duration. However, the speed of the supersonic ionization wave at the end of the laser irradiation is always maintained at 1.5 to 1.7 times that of the ion acoustic wave under the optimal initial density conditions.

  11. Quenched dynamics in interacting one-dimensional systems: Appearance of current carrying steady states from initial domain wall density profiles

    NASA Astrophysics Data System (ADS)

    Lancaster, Jarrett; Gull, Emanuel; Mitra, Aditi

    2011-03-01

    Dynamics arising after an interaction quench in the quantum sine-Gordon model is studied for the case of a system initially prepared in a spatially inhomogeneous domain wall state. The time-evolution of the density, current and equal time correlation functions are studied using the truncated Wigner approximation (TWA) to which quantum corrections are added in order to set the limits on its validity. For weak to moderate strengths of the back-scattering interaction, the domain wall is found to spread out ballistically with the system within the light cone reaching a non-equilibrium steady-state characterized by a net current flow. A steady state current is also found to exist for a quench at the exactly solvable Luther-Emery point. The magnitude of the current decreases with increasing strength of the back-scattering interaction. The two-point correlation function of the variable canonically conjugate to the density reaches a steady state which is spatially oscillating at a wavelength which is inversely related to the current. This was was supported by NSF-DMR (Award no. 1004589).

  12. Short-term priority over exotic annuals increases the initial density and longer-term cover of native perennial grasses.

    PubMed

    Vaughni, Kurt J; Young, Truman P

    2015-04-01

    Temporal priority can affect individual performance and reproduction, as well as community assembly, but whether these effects persist over time remains unclear, and their demographic mechanisms have been little explored. The continued dominance of exotic annual grasses in California has been commonly attributed to their demonstrated early germination and rapid early growth relative to native perennial grasses. This advantage may play a crucial role in the structure of California exotic annual grasslands, as well as in the practice of native grassland restoration. We tested whether a two-week planting advantage under field conditions increased individual survival, growth, and reproduction for four native perennial grass species and whether these effects persisted over three years. We show that short-term priority significantly increased the establishment success of' native perennial grasses. Increased density of native grass seedlings presaged later large increases in cover that were not evident in the first year after planting. Although priority effects at the individual level may diminish over time, short differences in emergence timing can have long-lasting effects on community structure. Earlier germination and faster initial growth of exotic annual species may help explain their unprecedented invasion and continued dominance of California grasslands. Finally, these results highlight the importance of priority effects for effective exotic annual control during native grassland restoration in California: initial control can increase the establishment of native perennial seedlings, which then results in long-term control by mature native individuals.

  13. Flow behavior of erythrocytes in microvessels and glass capillaries: effects of erythrocyte deformation and erythrocyte aggregation.

    PubMed

    Suzuki, Y; Tateishi, N; Soutani, M; Maeda, N

    1996-01-01

    Flow behavior of erythrocytes in microvessels and glass capillaries with an inner diameter of 10-50 microns was compared in relation to erythrocyte deformation and erythrocyte aggregation. This study was focused on the formation of a marginal cell-free layer, and the thickness was determined using an image processor. Human erythrocytes were perfused through a part of microvascular networks isolated from rabbit mesentery and through glass capillaries. Erythrocyte deformability was modified by treating erythrocytes with diamide, diazene-dicarboxylic acid bis[N,N-dimethylamide], and erythrocyte aggregation was accelerated by adding dextran (with a molecular weight of 70,400) to the perfusion medium. The thickness of the cell-free layer increased with an increase of the inner diameter of flow channel, with lowering the hematocrit, and with increasing the flow velocity of erythrocytes, in both microvessels and glass capillaries. Furthermore, the thickness of cell-free layer decreased with decreasing erythrocyte deformability, while it increased with accelerating erythrocyte aggregation. However, the alteration of the cell-free layer in response to the changes of these hemorheological conditions was more sensitive in microvessels than in glass capillaries. The present study concludes that flow behavior of erythrocytes in microvessels is qualitatively similar to, but quantitatively different from those in glass capillaries, as far as evaluated by the change of the thickness of the marginal cell-free layer.

  14. Recording of lymph flow dynamics in microvessels using correlation properties of scattered coherent radiation

    SciTech Connect

    Fedosov, I V; Tuchin, Valerii V; Galanzha, E I; Solov'eva, A V; Stepanova, T V

    2002-11-30

    The direction-sensitive method of microflow velocity measurements based on the space - time correlation properties of the dynamic speckle field is described and used for in vivo monitoring of lymph flow in the vessels of rat mesentery. The results of measurements are compared with the data obtained from functional video microscopy of the microvessel region. (laser biology and medicine)

  15. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    SciTech Connect

    Hingorani, V.; Brecher, P.

    1987-05-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either (6-/sup 14/C)glucose or (1-/sup 14/C)oleic acid and the incorporation of radioactivity into /sup 14/CO/sub 2/, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO/sub 2/ was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to /sup 14/CO/sub 2/ was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO/sub 2/ and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

  16. Improved Method of Ink-Gelatin Perfusion for Visualising Rat Retinal Microvessels

    PubMed Central

    Jianbin, Tong; Liang, Huang; Jufang, Huang; Hui, Wang; Dan, Chen; Leping, Zeng; Jin, Zhou; Xuegang, Luo

    2008-01-01

    To visualize completely rat retinal microvessels, the gelatin-ink perfusion condition was systematically optimized using von Willebrand factor (vWf) immunostaining as control. Whether the vessel showed by the new perfusion condition can be used for double label with neurons or glial cells in the same retina was also tested. Our results showed that infusing rats first with 20 ml of 37°C ink plus 3% gelatin at 140% rat mean arterial pressure (MAP), and subsequently with 20 ml of 37°C ink plus 5% gelatin at 180% rat MAP allowed the ink to completely fill the rat retinal microvessels. Rat retinal microvessels labeled by the perfusion method were more in number than that by vWf immunostaining. Moreover, our data, for the first time, displayed that the improved gelatin-ink perfusion had no effect on and caused no contamination to the following fluorogold labeling or immunostaining of retinal neurons or glial cells in the same tissue. These data suggest that the improved gelatin-ink perfusion technique is a superior method for morphological characterization of rat retinal microvessels, compatible to the double labeling of glial cells and neurons, and it extends the practical scale of the classic method. PMID:18989466

  17. Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation

    PubMed Central

    Kandasamy, Kathirvel; Parthasarathi, Kaushik

    2014-01-01

    The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement. PMID:25045895

  18. Cardioscopic observation of subendocardial microvessels in patients with coronary artery disease.

    PubMed

    Uchida, Yasuto; Kanai, Masahito; Maezawa, Yuko; Maezawa, Yoshiro; Shirai, Seiichiro; Nakagawa, Osamu; Uchida, Yasumi

    2011-01-01

    Coronary microvessels play a direct and critical role in determining the extent and severity of myocardial ischemia and cardiac function. However, because direct observation has never been performed in vivo, the functional properties of the individual microvesssels in patients with coronary artery disease remain unknown. Subendocardial coronary microvessels were observed by cardioscopy in 149 successive patients with coronary artery disease (81 with stable angina and 68 with old myocardial infarction). Twenty-four arterial microvessels (AMs) and 27 venous microvessels (VMs) were observed in the left ventricular subendocardium. All 12 AMs and 13 of 14 VMs that were located in normokinetic-to-hypokinetic left ventricular wall segments were filled with blood during diastole and were collapsed during systole. In contrast, 8 of 12 AMs and 9 of 13 VMs that were located in akinetic-to-dyskinetic wall segments were filled with blood during systole and were collapsed during diastole. There were no significant correlations between the timing of blood filling and the severity of coronary stenosis and collateral development. In patients with coronary artery disease, the timing of blood filling of AMs and VMs was dependent on the regional left ventricular contractile state; during diastole when contraction was preserved and during systole when it was not. It remains to be elucidated whether and how blood filling is disturbed in other categories of heart disease.

  19. Calponin and caldesmon cellular domains in reacting microvessels following traumatic brain injury.

    PubMed

    Kreipke, Christian W; Morgan, Noah C; Petrov, Theodor; Rafols, Jose A

    2006-05-01

    Calponin (Cp) and caldesmon (Cd) are actin-binding proteins involved in the regulation of smooth muscle (SM) tone during blood vessel contraction. While in vitro studies have reported modifications of these proteins during vessel contractility, their role in vivo remains unclear. Traumatic brain injury (TBI) causes disruption of cerebral microvascular tone, leading to sustained contractility in reacting microvessels and cerebral hypoperfusion. This study aimed to determine the spatial and temporal expressions of Cp and Cd in rat cerebral cortical and hippocampal microvessels post-TBI. Reacting microvessels were analyzed in control, 4, 24, and 48 h post-injury. Single and double immunocytochemical techniques together with semiquantitative analyses revealed a Cp upregulation in SM at all time frames post-TBI; with the protein migrating from SM cytosol to the vicinity of the cell membrane. Similarly, Cd immunoreactivity significantly increased in both SM and endothelial cells (En). However, while Cp and Cd in SM remained elevated, their levels in En returned to normal at 48 h post-TBI. The results suggest that Cp and Cd levels increase while compartmentalizing to specific subcellular domains. These changes are temporally associated with modifications in the cytoskeleton and contractile apparatus of SM and En during blood vessel contractility. Furthermore, these changes may underlie the state of sustained contractility and hypoperfusion observed in reacting microvessels after TBI.

  20. Influence of the initial parameters of the magnetic field and plasma on the spatial structure of the electric current and electron density in current sheets formed in helium

    SciTech Connect

    Ostrovskaya, G. V.; Markov, V. S.; Frank, A. G.

    2016-01-15

    The influence of the initial parameters of the magnetic field and plasma on the spatial structure of the electric current and electron density in current sheets formed in helium plasma in 2D and 3D magnetic configurations with X-type singular lines is studied by the methods of holographic interferometry and magnetic measurements. Significant differences in the structures of plasma and current sheets formed at close parameters of the initial plasma and similar configurations of the initial magnetic fields are revealed.

  1. The effect of concentration, thermal history and cell seeding density on the initial mechanical properties of agarose hydrogels.

    PubMed

    Buckley, Conor T; Thorpe, Stephen D; O'Brien, Fergal J; Robinson, Anthony J; Kelly, Daniel J

    2009-10-01

    Agarose hydrogels are commonly used for cartilage tissue engineering studies and to provide a three dimensional environment to investigate cellular mechanobiology. Interpreting the results of such studies requires accurate quantification of the mechanical properties of the hydrogel. There is significant variation in the reported mechanical properties of agarose hydrogels, and little is reported on the influence of factors associated with mixing these hydrogels with cell suspensions on their initial mechanical properties. The objective of this study was to determine the influence of agarose concentration, the cooling rate during gelation, the thermal history following gelation and the cell seeding density on the initial mechanical properties of agarose hydrogels. The average ramp modulus of 2% agarose gel in tension was 24.9 kPa (+/-1.7, n=10), compared with 55.6 kPa (+/-0.5, n=10) in compression. The average tensile equilibrium modulus was 39.7 kPa (+/-5.7, n=6), significantly higher than the compressive equilibrium modulus of 14.2 kPa (+/-1.6, n=10). The equilibrium and dynamic compressive modulus of agarose hydrogels were observed to reduce if maintained at 37 ( composite function)C following gelation compared with samples maintained at room temperature. Depending on the methodology used to encapsulate chondrocytes within agarose hydrogels, the equilibrium compressive modulus was found to be significantly higher for acellular 2% agarose gels compared with 2% agarose gels seeded at approximately 40 x 10(6) cells/mL. These results have important implications for interpreting the results of chondrocyte mechanobiology studies in agarose hydrogels.

  2. The Involvement of Pial Microvessels in Leukocyte Invasion after Mild Traumatic Brain Injury

    PubMed Central

    Shan, Rongzi; Thomasian, Nicole; Chodobski, Adam

    2016-01-01

    The pathophysiological mechanisms underlying mild traumatic brain injury (mTBI) are not well understood, but likely involve neuroinflammation. Here the controlled cortical impact model of mTBI in rats was used to test this hypothesis. Mild TBI caused a rapid (within 6 h post-mTBI) upregulation of synthesis of TNF-α and IL-1β in the cerebral cortex and hippocampus, followed by an increase in production of neutrophil (CXCL1–3) and monocyte (CCL2) chemoattractants. While astrocytes were not a significant source of CXC chemokines, they highly expressed CCL2. An increase in production of CXC chemokines coincided with the influx of neutrophils into the injured brain. At 6 h post-mTBI, we observed a robust influx of CCL2-expressing neutrophils across pial microvessels into the subarachnoid space (SAS) near the injury site. Mild TBI was not accompanied by any significant influx of neutrophils into the brain parenchyma until 24 h after injury. This was associated with an early induction of expression of intercellular adhesion molecule 1 on the endothelium of the ipsilateral pial, but not intraparenchymal, microvessels. At 6 h post-mTBI, we also observed a robust influx of neutrophils into the ipsilateral cistern of velum interpositum (CVI), a slit-shaped cerebrospinal fluid space located above the 3rd ventricle with highly vascularized pia mater. From SAS and CVI, neutrophils appeared to move along the perivascular spaces to enter the brain parenchyma. The monocyte influx was not observed until 24 h post-mTBI, and these inflammatory cells predominantly entered the ipsilateral SAS and CVI, with a limited invasion of brain parenchyma. These observations indicate that the endothelium of pial microvessels responds to injury differently than that of intraparenchymal microvessels, which may be associated with the lack of astrocytic ensheathment of cerebrovascular endothelium in pial microvessels. These findings also suggest that neuroinflammation represents the potential

  3. Proteomic and transcriptomic study of brain microvessels in neonatal and adult mice

    PubMed Central

    Porte, Baptiste; Chatelain, Clémence; Hardouin, Julie; Derambure, Céline; Zerdoumi, Yasmine; Hauchecorne, Michèle; Dupré, Nicolas; Bekri, Soumeya; Gonzalez, Bruno; Marret, Stéphane; Cosette, Pascal

    2017-01-01

    Infants born before 29 weeks gestation incur a major risk of preterm encephalopathy and subependymal/intracerebral/intraventricular haemorrhage. In mice, an ontogenic window of haemorrhage risk was recorded up to 5 days after birth in serpine1 knock-out animals. Using proteome and transcriptome approaches in mouse forebrain microvessels, we previously described the remodelling of extracellular matrix and integrins likely strengthening the vascular wall between postnatal day 5 (P5) and P10. Haemorrhage is the ultimate outcome of vessel damage (i.e., during ischaemia), although discreet vessel insults may be involved in the aetiology of preterm encephalopathy. In this study, we examined proteins identified by mass spectrometry and segregating in gene ontology pathways in forebrain microvessels in P5, P10, and adult wild type mice. In parallel, comparative transcript levels were obtained using RNA hybridization microarrays and enriched biological pathways were extracted from genes exhibiting at least a two-fold change in expression. Five major biological functions were observed in those genes detected both as proteins and mRNA expression undergoing at least a two-fold change in expression in one or more age comparisons: energy metabolism, protein metabolism, antioxidant function, ion exchanges, and transport. Adult microvessels exhibited the highest protein and mRNA expression levels for a majority of genes. Energy metabolism–enriched gene ontology pathways pointed to the preferential occurrence of glycolysis in P5 microvessels cells versus P10 and adult preparations enriched in aerobic oxidative enzymes. Age-dependent levels of RNA coding transport proteins at the plasma membrane and mitochondria strengthened our findings based on protein data. The data suggest that immature microvessels have fewer energy supply alternatives to glycolysis than mature structures. In the context of high energy demand, this constraint might account for vascular damage and maintenance

  4. Garlic prevents ultrastructural alterations caused by dehydration in mouse cerebral microvessels.

    PubMed

    Fahim, M A; El-Sabban, F F

    2001-05-01

    Dehydration is known to significantly reduce both the time required for the first platelet aggregate and the time to full occlusion in photochemically-induced thrombosis, in vivo. Ultrastructural changes that contribute to such events remain unknown. Therefore, the effect of water deprivation for 24 hr, (as a model for dehydration) on the ultrastructure of mouse pial microvessels was investigated. The possible beneficial effect of garlic in preventing such ultrastructural changes was also investigated. Four groups of TO strain: control, control-garlic treated, dehydrated, and dehydrated-garlic treated male mice, 10/group, were used. Dehydration was induced by water deprivation for 24 hr. Garlic solution was i.p. injected at 0.1 ml/10g body weight. In urethane-anesthetized (2 mg/g, i.p.) mice, topical and transvessel bimodal fixation of pial microvessels was done with a phosphate buffered mixture of glutaraldehyde and paraformaldehyde, followed by a conventional electron microscopy procedure. Examination of control cerebral pial microvessels showed no evidence of cellular damage. Membranes of endothelial cells were intact. Within pial microvessels there was no evidence of platelet aggregation. Garlic treatments did not cause any ultrastructure abnormalities in control mice. Compared with control, dehydration caused the appearance of thrombi that consisted of platelet aggregates. Discoid platelets containing granules, spheroid degranulated platelets, and those with large pseudopodia were present in 80% of dehydrated mice. The venular endothelial surface of dehydrated mice revealed dilated profiles of endoplasmic reticulum and variously shaped vacuoles. Swelling of nuclear envelopes and mitochondrial distension were also present in dehydrated mice. Concomitant garlic treatment prevented most of these ultrastructural changes. These findings demonstrated the extent of damage to the pial microvessels in response to water deprivation and demonstrated the beneficial effect

  5. Relative blood velocity measurement in individual microvessels using the self-mixing effect in a fiber-coupled helium-neon laser.

    PubMed

    Ren, T; Nuttall, A L; Miller, J M

    1995-03-01

    A system has been developed for the measurement of relative blood velocity in micro-vessels by using the self-mixing effect of a laser. A helium-neon laser was coupled to a single-mode optical fiber and the pulled fiber tip (approximately 30 microns diameter) was positioned on a single microvessel. The backscattered Doppler-shifted laser light from moving red blood cells enters the laser cavity and modulates the laser output by influencing internal laser parameters. The signal of the laser output intensity change was produced using a fiber-coupled photodiode and processed by a signal processor. This processor yields an output signal proportional to the first moment of the power spectral density, i.e., the mean frequency of the Doppler shift, corresponding to the blood flow velocity on an arbitrary instrument scale. Results of the in vitro experiment demonstrated that the current method can detect moving particles in fluid and moving red blood cells in a small plastic tube. Data from the in vivo study showed that this system is capable of measuring relative blood velocity in arterioles and venules and can easily follow the cardiac cycle up to 360 beats/min. Primary data suggest that, in addition to high sensitivity, good spatial and temporal resolution, and convenience of use, the self-mixing technique may have an even greater capacity for analysis of blood flow in microvessels than explored in this study, since information on the absolute velocity and velocity distribution of red blood cells is available in self-mixing signal. Further study on its hematocrit dependence and particle bias effect is needed.

  6. Tyrosyl radical generated by myeloperoxidase is a physiological catalyst for the initiation of lipid peroxidation in low density lipoprotein.

    PubMed

    Savenkova, M L; Mueller, D M; Heinecke, J W

    1994-08-12

    Myeloperoxidase, a heme protein secreted by activated phagocytes, is expressed in human atherosclerotic lesions. The enzyme uses H2O2 generated by the cells to oxidize L-tyrosine to tyrosyl radical, a catalyst for protein dityrosine synthesis. We have explored the possibility that tyrosyl radical initiates lipid peroxidation, which may be of pivotal importance in transforming low density lipoprotein (LDL) into atherogenic particles. Exposure of LDL to L-tyrosine and activated human neutrophils caused peroxidation of LDL lipids. LDL oxidation required L-tyrosine but was independent of free metal ions; catalase and heme poisons were inhibitory. Incubation of LDL with L-tyrosine, myeloperoxidase, and H2O2 likewise caused lipid peroxidation, and this reaction was inhibited by heme poisons and catalase. Replacement of L-tyrosine with O-methyltyrosine, which cannot form tyrosyl radical, inhibited LDL oxidation by both activated neutrophils and myeloperoxidase. The antioxidants ascorbate and probucol, but not vitamin E, inhibited LDL oxidation by myeloperoxidase, H2O2, and L-tyrosine. Ascorbate blocked dityrosine synthesis, while probucol scavenged chain-propagating peroxyl radicals in the lipid phase of LDL. These results indicate that tyrosyl radical stimulates LDL lipid peroxidation. In striking contrast to other cell-mediated mechanisms for LDL oxidation, the myeloperoxidase-catalyzed reaction is independent of free metal ions. This raises the possibility that tyrosyl radical generated by myeloperoxidase is of physiological importance in making LDL atherogenic.

  7. Simulation of Deformation and Aggregation of Two Red Blood Cells in a Stenosed Microvessel by Dissipative Particle Dynamics.

    PubMed

    Xiao, Lanlan; Liu, Yang; Chen, Shuo; Fu, Bingmei

    2016-12-01

    The motion of two red blood cells in a stenosed microvessel was simulated using dissipative particle dynamics. The effects of intercellular interaction, red blood cell deformability and the initial cell orientation on the deformation and aggregation of the RBCs and on the flow resistance were investigated. The red blood cell membrane was treated as a three-dimensional coarse-grained network model and the intercellular interaction was modeled by the Morse potential based on a depletion-mediated assumption. It is shown that the flow resistance increases dramatically when the red blood cells enter into the stenosis and decreases rapidly as RBCs move away from the stenosis. Particularly, for a pair of stiffer red blood cells with the initial inclination angle of 90°, the maximum value of the flow resistance is larger; while a higher flow resistance can also come from a stronger aggregation. For a pair of stiffer red blood cells moving parallel to the main flow, when their positions are closer to the vessel wall at the upstream of the stenosis, the flow resistance increases due to the migration to the vessel center at the stenosis. In addition, for a pair of red blood cells with the initial inclination angle of 0°, the flow resistance from the aggregate formed by a pair of red blood cells with a larger deformation is higher.

  8. Ultra-high Speed Optical Imaging of Ultrasound-activated Microbubbles in Mesenteric Microvessels

    NASA Astrophysics Data System (ADS)

    Chen, Hong

    Ultrasound contrast agent microbubbles have gained widespread applications in diagnostic and therapeutic ultrasound. Animal studies of bioeffects induced by ultrasound-activated microbubbles have demonstrated that microbubbles can cause microvessel damage. Much scientific attention has been attracted to such microvascular bioeffects, not only because of the related safety concerns, but also because of the potential useful applications of microbubbles in the intravascular delivery of drugs and genetic materials into target tissues. A significant challenge in using microbubbles in medical ultrasound is the lack of knowledge about how the microbubbles behave in blood vessels when exposed to ultrasound and how their interactions with ultrasound cause vascular damage. Although extensive studies were performed in the past to study the dynamics of microbubbles, most of those studies were performed in vitro and did not directly address the clinical environment in which microbubbles are injected into blood vessels. In this thesis work, a synchronized optical-acoustic system was set up for ultrahigh speed imaging of insonated microbubbles in microvessels. The recorded images revealed the formation of microjets penetrating the microbubbles, as well as vessel distention (motion outward against the surrounding tissue) and vessel invagination (motion inward toward the lumen) caused by the expansion and collapse of the microbubbles, respectively. Contrary to current paradigms which propose that microbubbles damage vessels either by distending them or by forming liquid jets impinging on them, microbubbles translation and jetting were in the direction away from the nearest vessel wall; furthermore, invagination typically exceeded distention in arterioles and venules. Vessel invagination was found to be associated with vascular damage. These studies suggest that vessel invagination may be a newly discovered potential mechanism for vascular damage by ultrasound-activated microbubbles

  9. Relationships between initial population densities of Meloidogyne incognita race 2 and nematode population development in terms of variable soybean resistance

    PubMed Central

    Mc Donald, Alexander H.; De Waele, Dirk

    2010-01-01

    The effect of increasing initial population density levels (Pi) of Meloidogyne incognita race 2 on nematode population development and yield of a susceptible (Prima2000) and resistant (LS5995) soybean cultivar was investigated. Two experiments, one in a hail net cage and one in microplots, were conducted one each during two consecutive growing seasons at Potchefstroom in the North West Province of South Africa. Nematode reproduction was assessed by determining the number of eggs and second-stage juveniles (J2) in the rhizosphere and roots, egg masses, egg-laying females (ELF) and reproduction factor (Rf) values per root system at harvesting 110 days after planting. Percentage yield reduction in the two cultivars was also calculated. Strong non-linear relationships existed between all nematode variables as well as between Pi and percentage yield loss in both cultivars for both experiments in this study. Significantly higher numbers of eggs and J2, egg masses and ELF were maintained in the roots of the nematode-susceptible Prima2000 than in the resistant LS5995 from Pi = 100 and higher in both experiments. Rf values were inversely related to Pi for both cultivars and were lowest on LS5995, with Prima2000 maintaining significantly higher Rf values in both experiments. Yield loss in LS5995 was at least six times higher than that of Prima2000. The difference in monetary terms is demonstrated, although it is suggested that host plant resistance to plant-parasitic nematodes may not be sufficient as the only management tool in highly infested soils or in rotation systems including nematode susceptible crops. PMID:22736837

  10. Fracture Rates and Bone Density Among Postmenopausal Veteran and Non-Veteran Women From the Women’s Health Initiative

    PubMed Central

    LaFleur, Joanne; Rillamas-Sun, Eileen; Colón-Emeric, Cathleen S.; Knippenberg, Kristin A.; Ensrud, Kristine E.; Gray, Shelly L.; Cauley, Jane A.; LaCroix, Andrea Z.

    2016-01-01

    Purpose of the Study: Postmenopausal osteoporosis can impact quality-of-life even prefracture. To determine whether osteoporosis should be a greater concern in women Veterans versus non-Veterans, we compared fracture rates and bone mineral density (BMD) for Veterans and non-Veterans using Women’s Health Initiative data. Design and Methods: In this cohort study, participants were women aged 50–79 years. Outcomes were hip, central body, and limb fractures occurring during up to 19 years of follow-up and hip, spine, and whole body BMD collected three times over a 6-year period in a participant subsample. Covariates comprised risk factors for fracture, including fall history and other components of the World Health Organization Fracture Risk Assessment Tool (FRAX). Cox Proportional Hazards models were used to examine fracture rates for Veterans compared with non-Veterans. Results: Of 161,808 women, 145,521 self-identified as Veteran (n = 3,719) or non-Veteran (n = 141,802). Baseline FRAX scores showed that Veterans had higher 10-year probabilities for any major fracture (13.3 vs 10.2; p < .01) and hip fracture (4.1 vs 2.2; p < .01) compared with non-Veterans. The age-adjusted rate of hip fracture per 1,000 person-years for Veterans was 3.3 versus 2.4 for non-Veterans (p < .01). After adjustment, the hazards ratio for hip fracture was 1.24 (95% confidence interval 1.03–1.49) for Veterans versus non-Veterans. Hazards ratios at other anatomic sites did not differ by Veteran status. Mean BMD at baseline and at Years 3 and 6 also did not differ by Veteran status at any site. Implications: Women Veterans had an increased hip fracture rate not explained by differences in well-recognized fracture risk factors. PMID:26768394

  11. Relationships between initial population densities of Meloidogyne incognita race 2 and nematode population development in terms of variable soybean resistance.

    PubMed

    Fourie, Hendrika; Mc Donald, Alexander H; De Waele, Dirk

    2010-03-01

    The effect of increasing initial population density levels (Pi) of Meloidogyne incognita race 2 on nematode population development and yield of a susceptible (Prima2000) and resistant (LS5995) soybean cultivar was investigated. Two experiments, one in a hail net cage and one in microplots, were conducted one each during two consecutive growing seasons at Potchefstroom in the North West Province of South Africa. Nematode reproduction was assessed by determining the number of eggs and second-stage juveniles (J2) in the rhizosphere and roots, egg masses, egg-laying females (ELF) and reproduction factor (Rf) values per root system at harvesting 110 days after planting. Percentage yield reduction in the two cultivars was also calculated. Strong non-linear relationships existed between all nematode variables as well as between Pi and percentage yield loss in both cultivars for both experiments in this study. Significantly higher numbers of eggs and J2, egg masses and ELF were maintained in the roots of the nematode-susceptible Prima2000 than in the resistant LS5995 from Pi = 100 and higher in both experiments. Rf values were inversely related to Pi for both cultivars and were lowest on LS5995, with Prima2000 maintaining significantly higher Rf values in both experiments. Yield loss in LS5995 was at least six times higher than that of Prima2000. The difference in monetary terms is demonstrated, although it is suggested that host plant resistance to plant-parasitic nematodes may not be sufficient as the only management tool in highly infested soils or in rotation systems including nematode susceptible crops.

  12. The effect of initial number of trees per acre and thinning densities on timber yields from red pine plantations in the Lake States.

    Treesearch

    Allen L. Lundgren

    1981-01-01

    Describes an analysis of initial density and subsequent thinning options for red pine (Pinus resinosa Ait.) plantations in the Lake States. Results showed that the initial number of established trees per acres has a major impact on the amount and quality of timber product yields, with 200 trees per acre (500/ha) thinned to 120 square feet of basal area per acre (27.5...

  13. Local RBC aggregation disturbing blood fluidity and causing stasis in microvessels.

    PubMed

    McHedlishvili, George; Varazashvili, Manana; Gobejishvili, Leila

    2002-01-01

    Experiments in rat mesenterium were carried out under conditions when both pressure gradient in the chosen microvessels and their diameters were preserved constant. All details of the hemorheological events were directly visualized and documented by usage of appropriate microscopic video techniques. Intensified RBC aggregation locally produced in individual capillaries, immediately disturbs the normal blood flow structure inside their lumina and deranges the rheological properties of blood flow in the microvessels, which slows down till a full stop. The RBC aggregates gradually grow up due to addition of new cells, which become compressed and appear homogeneous. This usually interferes with restoration of blood flow in capillaries. Further the RBC aggregates can move slowly towards veins, while the flow accelerates immediately as soon as the aggregates reach the larger venules.

  14. Quantification of red blood cell deformation at high-hematocrit blood flow in microvessels.

    PubMed

    Alizadehrad, Davod; Imai, Yohsuke; Nakaaki, Keita; Ishikawa, Takuji; Yamaguchi, Takami

    2012-10-11

    The deformation of red blood cells in microvessels was investigated numerically for various vessel diameters, hematocrits, and shear rates. We simulated blood flow in circular channels with diameters ranging from 9 to 50 μm, hematocrits from 20% to 45%, and shear rates from 20 to 150 s(-1) using a particle-based model with parallel computing. The apparent viscosity predicted by the simulation was in good agreement with previous experimental results. We quantified the deformation of red blood cells as a function of radial position. The numerical results demonstrated that because of the shape transition in response to local shear stress and the wall effect, the radial variation of red blood cell deformation in relatively large microvessels could be classified into three different regions: near-center, middle, and near-wall regions. Effects of the local shear stress and wall varied with vessel diameter, hematocrit, and shear rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Analysis of lymph flow in microvessels by biomicroscopic and coherent optical methods

    NASA Astrophysics Data System (ADS)

    Galanzha, Ekateryna I.; Brill, Gregory E.; Tuchin, Valery V.; Ulyanov, Sergey S.; Solov'eva, Anastasiya V.; Sedykh, Alexey V.

    2000-04-01

    The lymph flow velocity in microvessels of rat mesentery was investigated by using biomicroscopic manual frame-by-frame technique with image processing system and speckle- interferometrical method. Lymph flow was observed in the majority of lymphatics. Lymph flow was registered in microvessels with phasic contractions and functioning valves. The lymphocytes motion in flow was measured. It was established that mean lymph flow velocity increased in vessels with phasic contractions and moderate concentration of lymphocytes in flow. The application of speckle- interferometry allowed us to estimate lymph flow on the whole with all stops, the increases and decreases of flow velocity. The parameters both of changes of a mean velocity and of spatial-temporal velocity distribution in lymph flow were calculated. Temporal changes of the parameter V showed a shuttle-type character of lymph flow velocity.

  16. Three-Dimensional Arrangement of Human Bone Marrow Microvessels Revealed by Immunohistology in Undecalcified Sections

    PubMed Central

    Wilhelmi, Verena; Seiler, Anja; Lampp, Katrin; Neff, Andreas; Guthe, Michael; Lobachev, Oleg

    2016-01-01

    The arrangement of microvessels in human bone marrow is so far unknown. We combined monoclonal antibodies against CD34 and against CD141 to visualise all microvessel endothelia in 21 serial sections of about 1 cm2 size derived from a human iliac crest. The specimen was not decalcified and embedded in Technovit® 9100. In different regions of interest, the microvasculature was reconstructed in three dimensions using automatic methods. The three-dimensional models were subject to a rigid semiautomatic and manual quality control. In iliac crest bone marrow, the adipose tissue harbours irregularly distributed haematopoietic areas. These are fed by networks of large sinuses, which are loosely connected to networks of small capillaries prevailing in areas of pure adipose tissue. Our findings are compatible with the hypothesis that capillaries and sinuses in human iliac crest bone marrow are partially arranged in parallel. PMID:27997569

  17. Effects of curvature and cell-cell interaction on cell adhesion in microvessels.

    PubMed

    Yan, W W; Liu, Y; Fu, B M

    2010-10-01

    It has been found that both circulating blood cells and tumor cells are more easily adherent to curved microvessels than straight ones. This motivated us to investigate numerically the effect of the curvature of the curved vessel on cell adhesion. In this study, the fluid dynamics was carried out by the lattice Boltzmann method (LBM), and the cell dynamics was governed by the Newton's law of translation and rotation. The adhesive dynamics model involved the effect of receptor-ligand bonds between circulating cells and endothelial cells (ECs). It is found that the curved vessel would increase the simultaneous bond number, and the probability of cell adhesion is increased consequently. The interaction between traveling cells would also affect the cell adhesion significantly. For two-cell case, the simultaneous bond number of the rear cell is increased significantly, and the curvature of microvessel further enhances the probability of cell adhesion.

  18. Microvessel reactivity changes in light-diode irradiation of blood (470 to 980 nm)

    NASA Astrophysics Data System (ADS)

    Petrishchev, Nikolai N.; Yantareva, Ludmila I.

    1998-01-01

    The effects of distant light diode irradiation with various spectrums of the trunk vessels on reactivity of microvessels in the small intestine mesentery treated with threshold doses of norepinephrine (NoE) are compared. The character of changes in reactivity of microvessels to NoE was found to depend on the wave length and irradiation dose. Ultraviolet irradiation (470 nm, 0.03 J/sm2) was noticed to increase reactivity of the vessels to NoE (vasoconstriction increase). In green light irradiation (540 nm, 0.3 J/sm2 sm2) no changes in reactivity were observed. Red light irradiation (670 nm, 2.0 J/sm2), infrared particular (980 nm, 1.0 J/sm2), lowered reactivity to NoE. Thus, noninvasive light-diode irradiation of the blood results in different systemic changes of endothelial dependent reactivity of microcirculation due to specify of photochemical processes involved.

  19. Effect of heat transfer on rotating electroosmotic flow through a micro-vessel: haemodynamical applications

    NASA Astrophysics Data System (ADS)

    Sinha, A.; Mondal, A.; Shit, G. C.; Kundu, P. K.

    2016-08-01

    This paper theoretically analyzes the heat transfer characteristics associated with electroosmotic flow of blood through a micro-vessel having permeable walls. The analysis is based on the Debye-Hückel approximation for charge distributions and the Navier-Stokes equations are assumed to represent the flow field in a rotating system. The velocity slip condition at the vessel walls is taken into account. The essential features of the rotating electroosmotic flow of blood and associated heat transfer characteristics through a micro-vessel are clearly highlighted by the variation in the non-dimensional flow velocity, volumetric flow rate and non-dimensional temperature profiles. Moreover, the effect of Joule heating parameter and Prandtl number on the thermal transport characteristics are discussed thoroughly. The study reveals that the flow of blood is appreciably influenced by the elctroosmotic parameter as well as rotating Reynolds number.

  20. Endothelin-1 decreases ethanolamine plasmalogen levels and evokes PAF production in brain microvessels.

    PubMed

    Collado, M Pilar; Latorre, Eduardo; Fernández, Inmaculada; Aragonés, M Dolores; Catalán, R Edgardo

    2003-11-01

    Treatment of brain microvessels with Endothelin-1 evoked a decrease in ethanolamine plasmalogen levels by calcium-independent phospholipase A(2). In contrast, the diacyl molecular forms of ethanolamine phospholipids were unaffected. Evidence also shows that Endothelin type A receptors are involved. Concomitantly, PAF production mediated by CoA-independent transacylase was observed. This is the first evidence of involvement of these pathways on the Endothelin-1 mechanism of action on the blood-brain barrier.

  1. Brain microvessel endothelin type A receptors are coupled to ceramide production.

    PubMed

    Collado, M Pilar; Latorre, Eduardo; Fernández, Inmaculada; Aragonés, M Dolores; Catalán, R Edgardo

    2003-06-20

    Treatment of brain microvessels with endothelin-1 evoked an early decrease in the sphingomyelin levels concomitantly with an increase in those of ceramides. These responses were time- and concentration-dependent. Evidence also shows that endothelin type A receptors are involved. This is the first report on the involvement of an agonist in the regulation of the ceramide signal transduction system on blood-brain barrier and shows a new pathway likely involved in the regulation of the cerebral microvascular functioning.

  2. Effects of Interleukin-6 on the Expression of Tight Junction Proteins in Isolated Cerebral Microvessels from Yearling and Adult Sheep

    PubMed Central

    Cohen, Susan S.; Min, May; Cummings, Erin E.; Chen, Xiaodi; Sadowska, Grazyna B.; Sharma, Surendra; Stonestreet, Barbara S.

    2013-01-01

    Objectives The blood-brain barrier is a selective diffusion barrier between brain parenchyma and the intravascular compartment. Tight junctions (TJs) are integral components of the blood-brain barrier. Pro-inflammatory cytokines are important in the pathogenesis of brain injury and could modify the protein constituents of TJs. We hypothesized that IL-6 down-regulates key protein constituents of endothelial TJs (e.g., occludin and claudin-5). Methods We examined the effects of IL-6 on TJ protein expression using an in vitro blood-brain barrier model. We isolated microvessels from yearling and adult ovine cerebral cortex and placed them into culture with IL-6 concentrations of 0 (control, phosphate buffered saline), 1, 10, and 100 ng/mL for 24 hours. Cerebral microvessels were harvested, Western immunoblot performed for occludin and claudin-5, densitometry performed, and results expressed as a ratio to control values. Results Western immunoblot analysis showed that treatment with 100 ng/ml of IL-6, but not the lower concentrations, reduced (P<0.05) occludin expression in microvessels from yearling and adult sheep, and claudin-5 in microvessels from adult sheep However, treatment with 10 ng/ml of IL-6 increased claudin-5 in microvessels from yearling sheep. The percent of lactate dehydrogenase released from the microvessels into the surrounding media was not increased by IL-6 treatment, suggesting that the reductions in TJ proteins did not result from cell death. Treatment of adult cerebral cortical microvessels with IL-6 pre-incubated with anti-IL-6 monoclonal antibodies partially attenuated the reduction in claudin-5. Conclusion We conclude that IL-6 modulates tight junction protein expression in cerebral cortical microvessels from yearling and adult sheep. PMID:23867217

  3. The flow of red blood cells in stenosed microvessels and the influence of red blood cells on wall-bounded rolling motion of microparticles

    NASA Astrophysics Data System (ADS)

    Vahidkhah, Koohyar; Balogh, Peter; Bagchi, Prosenjit

    2015-11-01

    In the first part of this work, we consider a 3D computational study of the flow of deformable red blood cells in stenosed microvessels. We observe that the apparent viscosity of blood increases by several folds, and the rate of increase with increasing vessel diameter is also higher than that in non-stenosed vessels, implying an enhancement of the well-known Fahraeus-Lindqvist effect. The flow of the red blood cells causes time-dependent fluctuations in the blood flow rate. The RMS of the flow rate oscillations in the stenosed vessel is observed to be significantly higher than that in the non-stenosed vessel. Furthermore, several folds increase in the Eulerian velocity fluctuations and a transient flow reversal upstream the stenosed region are also observed, which would not occur in absence of the cells. In the second part, we consider the adhesive rolling motion of wall-bounded microparticles in presence of flowing red blood cells in microvessels. We observe two contradictory role of the red blood cells: On one hand, the cells facilitate the establishment of the particle-wall contact, and, thereby, initiation of adhesion. On the other hand, they augment the rolling velocity of the particles. Implications of these results on the optimal design of drug carriers are discussed.

  4. Simulation of a single red blood cell flowing through a microvessel stenosis using dissipative particle dynamics.

    PubMed

    Xiao, L L; Chen, S; Lin, C S; Liu, Y

    2014-03-01

    The motion and deformation of a single red blood cell flowing through a microvessel stenosis was investigated employing dissipative particle dynamics (DPD) method. The numerical model considers plasma, cytoplasm, the RBC membrane and the microvessel walls, in which a three dimensional coarse-grained spring RBC. The suspending plasma was modelled as an incompressible Newtonian fluid and the vessel walls were regarded as rigid body. The body force exerted on the free DPD particles was used to drive the flow. A modified bounce-back boundary condition was enforced on the membrane to guarantee the impenetrability. Adhesion of the cell to the stenosis vessel surface was mediated by the interactions between receptors and ligands. Firstly, the motion of a single RBC in a microfluidic channel was simulated and the results were found in agreement with the experimental data cited by [1]. Then the mechanical behavior of the RBC in the microvessel stenosis was studied. The effects of the bending rigidity of membrane, the size of the stenosis and the driven body force on the deformation and motion of red blood cell were discussed.

  5. The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls.

    PubMed

    Wang, Gou-Jen; Lin, Yan-Cheng; Hsu, Shan-Hui

    2010-10-01

    Poly (lactic-co-glycolic acid) (PLGA) is one of the most commonly used biodegradable, biocompatible materials. Nanostructured PLGA has immense potential for application in tissue engineering. In this article we discuss a novel approach for the fabrication of PLGA microvessel scaffolds with nanostructured inner walls. In this novel nano-patterning approach, the thermal reflow technique is first adapted to fabricate a semi-cylindrical photoresist master mold. A thin film of titanium and a thin film of aluminum are sputtered in sequence on the semi-cylindrical microvessel network. Aluminum foil anodization is then executed to transform the aluminum thin film into a porous anodic aluminum oxide (AAO) film. During the casting process a PLGA solution is cast on the AAO film to build up semi-cylindrical PLGA microstructures with nanostructured inner walls after which inductive coupled plasma (ICP) is implemented to assist bonding of the two PLGA structures. The result is the building of a network of microchannels with nano-patterned inner walls. Bovine endothelial cells (BECs) are carefully cultured in the scaffold via semi-dynamic seeding for 7 days. Observations show that the BECs grew more separately in a nano-patterned microvessel scaffold than they did in a smooth surface scaffold.

  6. Cell-free layer and wall shear stress variation in microvessels.

    PubMed

    Yin, Xuewen; Zhang, Junfeng

    2012-01-01

    In this study, we simulated multiple red blood cells flowing through straight microvessels with the immersed-boundary lattice-Boltzmann model to examine the shear stress variation on the microvessel surface and its relation to the properties of cell-free layer. Significant variation in shear stress has been observed due to the irregular configuration of blood cells flowing near the microvessel wall. A low shear stress is typically found at locations where there is a cell flowing close to the wall, and a large shear stress at locations with a relatively wide gap between cell and wall. This relationship between the shear stress magnitude and the distance between cell and wall has been attributed to the reverse pressure difference developed between the front and rear sides of a cell flowing near the vessel wall. We further studied the effects of several hemodynamic factors on the variation of shear stress, including the cell deformability, the flow rate, and the aggregation among red blood cells. These simulations show that the shear stress variation is less profound in situations with wider cell-free layers, since the reverse pressure difference around the edge cells is less evident, and the influence of this pressure difference on wall shear stress becomes weaker. This study also demonstrates the complexity of the flow field in the gap between cell and wall. More precise experimental techniques are required accurately measure such shear stress variation in microcirculation.

  7. Bone Mineral Density as a Predictor of Subsequent Wrist Fractures: Findings From the Women's Health Initiative Study

    PubMed Central

    Hovey, Kathleen M.; Andrews, Christopher A.; Cauley, Jane A.; Manson, JoAnn E.; Wactawski-Wende, Jean; Wright, Nicole C.; Li, Wenjun; Beavers, Kristen; Curtis, Jeffrey R.; LeBoff, Meryl S.

    2015-01-01

    Context: Wrist fractures are common among postmenopausal women. Associations of bone mineral density (BMD) and 10-year predicted risk of major osteoporotic fracture (MOF) with wrist fractures are poorly characterized. Objective: The objective was to examine associations between the Fracture Risk Assessment Tool (FRAX)-predicted risk of MOF, BMD, BMD change, and wrist fracture. Design: This was a prospective observational study with a mean follow-up of 8.5 years. Setting: This study included 40 US centers. Participants: A total of 11 392 participants from the Women's Health Initiative BMD Cohort aged 50–79 years at baseline were included in this study. Interventions: None. Main Outcome: The goal was to measure incident wrist fracture. Results: A FRAX-predicted MOF risk ≥9.3% identified 17% of the women aged <65 years who subsequently experienced wrist fracture. Each one standard deviation lower BMD was associated with higher wrist fracture risk, with adjusted hazard ratio (95% confidence interval) of 1.66 (1.42–1.93) for femoral neck (FN) BMD and 1.45 (1.28–1.64) for lumbar spine BMD. Compared with FN BMD T score ≥ −1.0, wrist fracture adjusted hazard ratios (95% confidence interval) were: 1.51 (1.06–2.16) for a T score between −1.01 and −1.49; 1.93 (1.36–2.72) for T score between −1.50 and −1.99; 2.52 (1.77–3.60) for a T score between −2.00 and −2.49; and 2.65 (1.78–3.95) for a T score ≤ −2.5. Decrease in FN BMD between baseline and year 3 was associated with increased risk of subsequent wrist fracture; however, change in lumbar spine BMD was not. Conclusions: Lumbar spine and femoral neck BMDs were associated with incident wrist fracture, but the FRAX threshold recommended to identify screening candidates did not identify the majority of women who subsequently experienced wrist fracture. Improved understanding of determinants of wrist fractures is warranted. PMID:26367200

  8. Fracture Rates and Bone Density Among Postmenopausal Veteran and Non-Veteran Women From the Women's Health Initiative.

    PubMed

    LaFleur, Joanne; Rillamas-Sun, Eileen; Colón-Emeric, Cathleen S; Knippenberg, Kristin A; Ensrud, Kristine E; Gray, Shelly L; Cauley, Jane A; LaCroix, Andrea Z

    2016-02-01

    Postmenopausal osteoporosis can impact quality-of-life even prefracture. To determine whether osteoporosis should be a greater concern in women Veterans versus non-Veterans, we compared fracture rates and bone mineral density (BMD) for Veterans and non-Veterans using Women's Health Initiative data. In this cohort study, participants were women aged 50-79 years. Outcomes were hip, central body, and limb fractures occurring during up to 19 years of follow-up and hip, spine, and whole body BMD collected three times over a 6-year period in a participant subsample. Covariates comprised risk factors for fracture, including fall history and other components of the World Health Organization Fracture Risk Assessment Tool (FRAX). Cox Proportional Hazards models were used to examine fracture rates for Veterans compared with non-Veterans. Of 161,808 women, 145,521 self-identified as Veteran (n = 3,719) or non-Veteran (n = 141,802). Baseline FRAX scores showed that Veterans had higher 10-year probabilities for any major fracture (13.3 vs 10.2; p < .01) and hip fracture (4.1 vs 2.2; p < .01) compared with non-Veterans. The age-adjusted rate of hip fracture per 1,000 person-years for Veterans was 3.3 versus 2.4 for non-Veterans (p < .01). After adjustment, the hazards ratio for hip fracture was 1.24 (95% confidence interval 1.03-1.49) for Veterans versus non-Veterans. Hazards ratios at other anatomic sites did not differ by Veteran status. Mean BMD at baseline and at Years 3 and 6 also did not differ by Veteran status at any site. Women Veterans had an increased hip fracture rate not explained by differences in well-recognized fracture risk factors. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Implant-assisted magnetic drug targeting in permeable microvessels: Comparison of two-fluid statistical transport model with experiment

    NASA Astrophysics Data System (ADS)

    ChiBin, Zhang; XiaoHui, Lin; ZhaoMin, Wang; ChangBao, Wang

    2017-03-01

    In experiments and theoretical analyses, this study examines the capture efficiency (CE) of magnetic drug carrier particles (MDCPs) for implant-assisted magnetic drug targeting (IA-MDT) in microvessels. It also proposes a three-dimensional statistical transport model of MDCPs for IA-MDT in permeable microvessels, which describes blood flow by the two-fluid (Casson and Newtonian) model. The model accounts for the permeable effect of the microvessel wall and the coupling effect between the blood flow and tissue fluid flow. The MDCPs move randomly through the microvessel, and their transport state is described by the Boltzmann equation. The regulated changes and factors affecting the CE of the MDCPs in the assisted magnetic targeting were obtained by solving the theoretical model and by experimental testing. The CE was negatively correlated with the blood flow velocity, and positively correlated with the external magnetic field intensity and microvessel permeability. The predicted CEs of the MDCPs were consistent with the experimental results. Additionally, under the same external magnetic field, the predicted CE was 5-8% higher in the IA-MDT model than in the model ignoring the permeability effect of the microvessel wall.

  10. Intratumoral α-SMA enhances the prognostic potency of CD34 associated with maintenance of microvessel integrity in hepatocellular carcinoma and pancreatic cancer.

    PubMed

    Wang, Wen-Quan; Liu, Liang; Xu, Hua-Xiang; Luo, Guo-Pei; Chen, Tao; Wu, Chun-Tao; Xu, Yong-Feng; Xu, Jin; Liu, Chen; Zhang, Bo; Long, Jiang; Tang, Zhao-You; Yu, Xian-Jun

    2013-01-01

    Microvessel density (MVD) as an angiogenesis predictor is inefficient per se in cancer prognosis. We evaluated prognostic values of combining intratumoral alpha-smooth muscle actin (α-SMA)-positive stromal cell density and MVD after curative resection in hypervascular hepatocellular carcinoma (HCC) and hypovascular pancreatic cancer (PC). Tissue microarrays were constructed from tumors of 305 HCC and 57 PC patients who underwent curative resection and analyzed for α-SMA and CD34 expression by immunostaining. Prognostic values of these two proteins and other clinicopathological features were examined. Both low α-SMA density and high MVD-CD34 were associated in HCC with the presence of intrahepatic metastasis and microvascular invasion, and they were related to lymph node involvement and microvascular invasion in PC (p<0.05). Although CD34 alone, but not α-SMA, was an independent prognostic factor for overall survival and recurrence-free survival, the combination of low α-SMA and high CD34 was a predictor of worst prognosis for both types of tumors and had a better power to predict patient death and early recurrence (p<0.01). Furthermore, the results show that distribution of most of the α-SMA-positive cells and vascular endothelial cells overlap, showing major colocalization on vascular walls. Poor microvessel integrity, as indicated by high MVD, together with low perivascular α-SMA-positive cell coverage is associated with early recurrence, unfavorable metastasis, and short survival after tumor resection. This finding highlights the significance of vascular quality in tumor progression, which provides an optimized complement to vascular quantity in prognosis of postoperative patients.

  11. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    SciTech Connect

    Wolfe, Adam R.; Atkinson, Rachel L.; Reddy, Jay P.; Debeb, Bisrat G.; Larson, Richard; Li, Li; Masuda, Hiroko; Brewer, Takae; Atkinson, Bradley J.; Brewster, Abeena; Ueno, Naoto T.; Woodward, Wendy A.

    2015-04-01

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  12. G Clustering Is Important for the Initiation of Transcription-Induced R-Loops In Vitro, whereas High G Density without Clustering Is Sufficient Thereafter▿ †

    PubMed Central

    Roy, Deepankar; Lieber, Michael R.

    2009-01-01

    R-loops form cotranscriptionally in vitro and in vivo at transcribed duplex DNA regions when the nascent RNA is G-rich, particularly with G clusters. This is the case for phage polymerases, as used here (T7 RNA polymerase), as well as RNA polymerases in bacteria, Saccharomyces cerevisiae, avians, mice, and humans. The nontemplate strand is left in a single-stranded configuration within the R-loop region. These structures are known to form at mammalian immunoglobulin class switch regions, thus exposing regions of single-stranded DNA for the action of AID, a single-strand-specific cytidine deaminase. R-loops form by thread-back of the RNA onto the template DNA strand, and here we report that G clusters are extremely important for the initiation phase of R-loop formation. Even very short regions with one GGGG sequence can initiate R-loops much more efficiently than random sequences. The high efficiencies observed with G clusters cannot be achieved by having a very high G density alone. Annealing of the transcript, which is otherwise disadvantaged relative to the nontemplate DNA strand because of unfavorable proximity while exiting the RNA polymerase, can offer greater stability if it occurs at the G clusters, thereby initiating an R-loop. R-loop elongation beyond the initiation zone occurs in a manner that is not as reliant on G clusters as it is on a high G density. These results lead to a model in which G clusters are important to nucleate the thread-back of RNA for R-loop initiation and, once initiated, the elongation of R-loops is primarily determined by the density of G on the nontemplate DNA strand. Without both a favorable R-loop initiation zone and elongation zone, R-loop formation is inefficient. PMID:19307304

  13. G clustering is important for the initiation of transcription-induced R-loops in vitro, whereas high G density without clustering is sufficient thereafter.

    PubMed

    Roy, Deepankar; Lieber, Michael R

    2009-06-01

    R-loops form cotranscriptionally in vitro and in vivo at transcribed duplex DNA regions when the nascent RNA is G-rich, particularly with G clusters. This is the case for phage polymerases, as used here (T7 RNA polymerase), as well as RNA polymerases in bacteria, Saccharomyces cerevisiae, avians, mice, and humans. The nontemplate strand is left in a single-stranded configuration within the R-loop region. These structures are known to form at mammalian immunoglobulin class switch regions, thus exposing regions of single-stranded DNA for the action of AID, a single-strand-specific cytidine deaminase. R-loops form by thread-back of the RNA onto the template DNA strand, and here we report that G clusters are extremely important for the initiation phase of R-loop formation. Even very short regions with one GGGG sequence can initiate R-loops much more efficiently than random sequences. The high efficiencies observed with G clusters cannot be achieved by having a very high G density alone. Annealing of the transcript, which is otherwise disadvantaged relative to the nontemplate DNA strand because of unfavorable proximity while exiting the RNA polymerase, can offer greater stability if it occurs at the G clusters, thereby initiating an R-loop. R-loop elongation beyond the initiation zone occurs in a manner that is not as reliant on G clusters as it is on a high G density. These results lead to a model in which G clusters are important to nucleate the thread-back of RNA for R-loop initiation and, once initiated, the elongation of R-loops is primarily determined by the density of G on the nontemplate DNA strand. Without both a favorable R-loop initiation zone and elongation zone, R-loop formation is inefficient.

  14. Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases1

    PubMed Central

    Zozulya, Alla L.; Reinke, Emily; Baiu, Dana C.; Karman, Jozsef; Sandor, Matyas; Fabry, Zsuzsanna

    2007-01-01

    Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the exact mechanism regulating their traffic into the CNS remains to be defined. We now report that MIP-1α increases the transmigration of bone marrow-derived, GFP-labeled DCs across brain microvessel endothelial cell monolayers. Furthermore, occludin, an important element of endothelial tight junctions, is reorganized when DCs migrate across brain capillary endothelial cell monolayers without causing significant changes in the barrier integrity as measured by transendothelial electrical resistance. We show that DCs produce matrix metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both baseline and MIP-1α -induced DC transmigration. These observations suggest that DC transmigration across brain endothelial cell monolayers is partly MMP dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 costimulatory molecules and induce T cell proliferation, indicating that the transmigration of DCs across brain endothelial cell monolayers contributes to the maintenance of DC Ag-presenting function. The MMP dependence of DC migration across brain endothelial cell monolayers raises the possibility that MMP blockers may decrease the initiation of T cell recruitment and neuroinflammation in the CNS. PMID:17182592

  15. Population age and initial density in a patchy environment affect the occurrence of abrupt transitions in a birth-and-death model of Taylor's law

    USGS Publications Warehouse

    Jiang, Jiang; DeAngelis, Donald L.; Zhang, B.; Cohen, J.E.

    2014-01-01

    Taylor's power law describes an empirical relationship between the mean and variance of population densities in field data, in which the variance varies as a power, b, of the mean. Most studies report values of b varying between 1 and 2. However, Cohen (2014a) showed recently that smooth changes in environmental conditions in a model can lead to an abrupt, infinite change in b. To understand what factors can influence the occurrence of an abrupt change in b, we used both mathematical analysis and Monte Carlo samples from a model in which populations of the same species settled on patches, and each population followed independently a stochastic linear birth-and-death process. We investigated how the power relationship responds to a smooth change of population growth rate, under different sampling strategies, initial population density, and population age. We showed analytically that, if the initial populations differ only in density, and samples are taken from all patches after the same time period following a major invasion event, Taylor's law holds with exponent b=1, regardless of the population growth rate. If samples are taken at different times from patches that have the same initial population densities, we calculate an abrupt shift of b, as predicted by Cohen (2014a). The loss of linearity between log variance and log mean is a leading indicator of the abrupt shift. If both initial population densities and population ages vary among patches, estimates of b lie between 1 and 2, as in most empirical studies. But the value of b declines to ~1 as the system approaches a critical point. Our results can inform empirical studies that might be designed to demonstrate an abrupt shift in Taylor's law.

  16. Classification of nasopharyngeal microvessels detected by narrow band imaging endoscopy and its role in the diagnosis of nasopharyngeal carcinoma.

    PubMed

    Ni, Xiao-Guang; Zhang, Qing-Qing; Wang, Gui-Qi

    2017-05-01

    The new NBI classification of nasopharyngeal mucosal microvessels was helpful in differential diagnosis for benign and malignant lesions of the nasopharyngeal region. NBI endoscopy facilitates the detection of superficial nasopharyngeal lesions and might enable early diagnoses of NPC. To propose a new microvessel diagnostic classification using narrow band imaging (NBI) endoscopy and to investigate the role of an NBI classification in the diagnosis of nasopharyngeal carcinoma (NPC). Between January 2009 and December 2010, a total of 290 patients with a suspected nasopharyngeal tumor were enrolled in this study. The NBI endoscopic system was used to examine the nasopharynx. Each lesion was observed by NBI endoscopy and judged according to the detailed morphologic findings of epithelial microvessels. The superficial microvessel patterns were classified into five types (types I-V). The diagnostic effectiveness of NBI for benign and malignant nasopharyngeal lesions was evaluated. Approximately 93.5% (29/31) of lymphoid hyperplasia appeared as the type II microvessel pattern under NBI endoscopy, whereas 96.2% (51/53) of nasopharyngeal radiation-induced inflammation exhibited the type III or IV microvessel pattern. The characteristics of NPC under NBI endoscopy mainly appeared as a type V microvessel pattern (79.5%, 167/210), and the sensitivity, specificity, predictive value (PPV), and negative predictive value (NPV) of type V in the diagnosis of NPC were 79.5%, 91.3%, 96.0%, and 62.9%, respectively. NBI endoscopy could significantly improve the detection of superficial lesions (χ(2 )=( )12.789, p = .000).

  17. A tropical cyclone dynamic initialization technique using high temporal and spatial density atmospheric motion vectors and airborne field campaign data

    NASA Astrophysics Data System (ADS)

    Hendricks, E. A.; Bell, M. M.; Elsberry, R. L.; Velden, C.

    2016-12-01

    A new tropical cyclone dynamic initialization technique is described and tested. The technique uses the triple-nested Coupled Ocean-Atmosphere Mesoscale Prediction System-Tropical Cyclones (COAMPS-TC) (with horizontal grid spacings of 45-,15-, and 5-km, respectively) in conjunction with the Spline Analysis at Mesoscale Utilizing Radar and Aircraft Instrumentation (SAMURAI). A proof-of-concept demonstration of this technique is given for Hurricane Joaquin from the Office of Naval Research (ONR) Tropical Cyclone Intensity (TCI) field program conducted in 2015. High spatial and temporal resolution atmospheric motion vectors (AMVs), dropwindsondes from the Yankee Environmental Systems High Definition Sounding System (HDSS), and surface wind speed retrievals from the Hurricane Imaging Radiometer (HIRAD) are ingested into SAMURAI to produce increments, which are then used by the COAMPS-TC dynamic initialization scheme to produce consistent dynamic and thermodynamically balanced fields. This high temporal resolution (order of 10-15 minutes) incremental dynamic initialization procedure has advantages over conventional methods in that a bogus vortex is not used, and existing asymmetries (including convective heating and upper and low level wind asymmetries) that exist in the TC are retained. The use of dynamic initialization also ensures improved vortex and environment balance, and consistency with the model physics. A preliminary verification of this new TC initialization scheme will be presented for the initialization and forecast of Hurricane Joaquin (2015).

  18. Direct phase selection of initial phases from single-wavelength anomalous dispersion (SAD) for the improvement of electron density and ab initio structure determination

    SciTech Connect

    Chen, Chung-De; Huang, Yen-Chieh; Chiang, Hsin-Lin; Hsieh, Yin-Cheng; Guan, Hong-Hsiang; Chuankhayan, Phimonphan; Chen, Chun-Jung

    2014-09-01

    A novel direct phase-selection method to select optimized phases from the ambiguous phases of a subset of reflections to replace the corresponding initial SAD phases has been developed. With the improved phases, the completeness of built residues of protein molecules is enhanced for efficient structure determination. Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (ϕ{sub 1} and ϕ{sub 2}) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θ{sub DS} list as a criterion to select optimized phases ϕ{sub am} from ϕ{sub 1} or ϕ{sub 2} of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases ϕ{sub SAD} has been developed. Based on this work, reflections with an angle θ{sub DS} in the range 35–145° are selected for an optimized improvement, where θ{sub DS} is the angle between the initial phase ϕ{sub SAD} and a preliminary density-modification (DM) phase ϕ{sub DM}{sup NHL}. The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination.

  19. Modeling and Validation of the Thermal Response of TDI Encapsulating Foam as a function of Initial Density

    SciTech Connect

    Dodd, Amanda B.; Larsen, Marvin E.

    2014-09-01

    TDI foams of nominal density from 10 to 45 pound per cubic foot were decomposed within a heated stainless steel container. The pressure in the container and temperatures measured by thermocouples were recorded with each test proceeding to an allowed maximum pressure before venting. Two replicate tests for each of four densities and two orientations in gravity produced very consistent pressure histories. Some thermal responses demonstrate random sudden temperature increases due to decomposition product movement. The pressurization of the container due to the generation of gaseous products is more rapid for denser foams. When heating in the inverted orientation, where gravity is in the opposite direction of the applied heat flux, the liquefied decomposition products move towards the heated plate and the pressure rises more rapidly than in the upright configuration. This effect is present at all the densities tested but becomes more pronounced as density of the foam is decreased. A thermochemical material model implemented in a transient conduction model solved with the finite element method was compared to the test data. The expected uncertainty of the model was estimated using the mean value method and importance factors for the uncertain parameters were estimated. The model that was assessed does not consider the effect of liquefaction or movement of gases. The result of the comparison is that the model uncertainty estimates do not account for the variation in orientation (no gravitational affects are in the model) and therefore the pressure predictions are not distinguishable due to orientation. Temperature predictions were generally in good agreement with the experimental data. Predictions for response locations on the outside of the can benefit from reliable estimates associated with conduction in the metal. For the lighter foams, temperatures measured on the embedded component fall well with the estimated uncertainty intervals indicating the energy transport

  20. Photoacoustic simulation of microvessel bleeding: spectral analysis and its implication for monitoring vascular-targeted treatments

    NASA Astrophysics Data System (ADS)

    Fadhel, Muhannad N.; Hysi, Eno; Zalev, Jason; Kolios, Michael C.

    2016-03-01

    The destruction of blood vessels is a commonly used cancer therapeutic strategy. Bleeding consequently follows and leads to the accumulation of blood in the interstitium. Photoacoustic (PA) imaging is well positioned to detect bleeding due to its sensitivity to hemoglobin. After treatment vascular disruption can occur within just a few hours, which leads to bleeding which might be detected using PA to assess therapeutic effectiveness. Deep micro-vessels cannot typically be resolved using acoustic-resolution PA. However, spectral analysis of PA signals may still permit assessment of bleeding. This paper introduces a theoretical model to simulate the PA signals from disrupted vessels using a fractal model. The fractal model uses bifurcated-cylinder bases to represent vascular trees. Vessels have circular absorption cross-sections. To mimic bleeding from blood vessels, the diffusion of hemoglobin from micro-vessels was simulated. The PA signals were computed and in the simulations were detected using a linear array transducer (30 MHz center frequency) for four different vascular trees (at 256 axial spatial locations/tree). The Fourier Transform of each beam-formed PA signal was computed and the power spectra were fitted to a straight line within the -6 dB bandwidth of the receiving transducer. When comparing the power spectra before and after simulated bleeding, the spectral slope and mid-band fit (MBF) parameters decreased by 0.12 dB/MHz and 2.12 dB, while the y-intercept did not change after 1 hour of simulated bleeding. The results suggest that spectral PA analysis is sensitive to changes in the concentration and spatial distribution of hemoglobin in tissue, and changes due to bleeding can be detected without the need to resolve individual vessels. The simulations support the applicability of PA imaging in cancer treatment monitoring by detecting micro-vessel disruption.

  1. The Natural Frequency of Nonlinear Oscillation of Ultrasound Contrast Agents in Microvessels

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2009-01-01

    Ultrasound Contrast Agent (UCAs) are under intensive investigation for their applications in physiological and molecular imaging and drug delivery. Prediction of the natural frequency of the oscillation of UCAs in microvessels has drawn increasing attention. To our knowledge, the existing models to predict the natural frequency of oscillation of UCAs in microvessels all apply the linear approximation and treat the blood vessel wall as a rigid boundary. In the potential applications of ultrasound imaging drug and gene delivery, the compliance of small vessels may play an important role in the bubble’s oscillation. The goal of this work is to provide a lumped-parameter model to study the natural frequency of nonlinear oscillation of UCAs in microvessels. Three types of the blood vessel conditions have been considered. i.e. rigid vessels, normal compliable vessels and vessels with increasing stiffness that could correspond to tumor vasculature. The corresponding bubble oscillation frequencies in the vessels with radius less than 100 μm are examined in detail. When a bubble with a radius of 4 μm is confined in a compliable vessel (inner radius 5 μm and length 100μm), the natural frequency of bubble oscillation increases by a factor of 1.7 as compared with a bubble in an unbounded field. The natural frequency of oscillation of a bubble in a compliable vessel increases with decreasing vessel size while decreasing with increasing values of vessel rigidity. This model suggests that contrast agent size, blood vessel size distribution and the type of vasculature should be comprehensively considered for choosing the transmitted frequency in ultrasound contrast imaging and drug delivery. PMID:17478030

  2. A comparative study of the spatial distribution of mast cells and microvessels in the foetal, adult human thymus and thymoma.

    PubMed

    Raica, Marius; Cimpean, Anca Maria; Nico, Beatrice; Guidolin, Diego; Ribatti, Domenico

    2010-02-01

    Mast cells (MCs) are widely distributed in human and animal tissues and have been shown to play an important role in angiogenesis in normal and pathological conditions. Few data are available about the relationship between MCs and blood vessels in the normal human thymus, and there are virtually no data about their distribution and significance in thymoma. The aim of this study was to analyse the spatial distribution of MCs and microvessels in the normal foetal and adult thymus and thymoma. Twenty biopsy specimens of human thymus, including foetal and adult normal thymus and thymoma were analysed. Double staining with CD34 and mast cell tryptase was used to count both mast cells and microvessels in the same fields. Computer-assisted image analysis was performed to characterize the spatial distribution of MCs and blood vessels in selected specimens. Results demonstrated that MCs were localized exclusively to the medulla. Their number was significantly higher in thymoma specimens as compared with adult and foetal normal specimens respectively. In contrast the microvessel area was unchanged. The analysis of the spatial distribution and relationship between MCs and microvessels revealed that only in the thymoma specimens was there a significant spatial association between MCs and microvessels. Overall, these data suggest that MCs do not contribute significantly to the development of the vascular network in foetal and adult thymus, whereas in thymoma they show a close relationship to blood vessels. This could be an expression of their involvement not only in endothelial cells but also in tumour cell proliferation.

  3. Modeling and simulation of illumination effects for evaluation of microvessels of the conjunctiva.

    PubMed

    Wick, C E; Loew, M H; Kurantsin-Mills, J

    1996-09-01

    We present the development of a comprehensive model that was undertaken to determine the relationships between the components of an image and the light intensity values present in the image of the microvessels of translucent tissues such as the bulbar conjunctiva. Experiments were conducted during the modeling process by use of a cylindrical microvessel embedded in a diffuse medium (phantom) on a reflecting background to affirm model components and simulations. The three-dimensional model was reduced to a single illumination plane with four regions of interest and modeled as Lambertian radiators and surfaces. The modeling showed that the top of the cylinder and its immediate vicinity are diffuse reflectors of light from the source plus light reflected from the background. The limbus of the cylinder is a diffuse reflector of the source and background illumination and a specular reflector of background reflections that achieve a high grazing angle with the cylinder. The immediate vicinity of the cylinder receives direct illumination from the source, but the light is partially obscured by the cylinder. The region beyond the shadow of the cylinder is a diffuse reflector of the overhead light. The diffuse medium additionally reflects the source and also attenuates the illumination reaching the other compo- rents of the scene. The direct and reflected illumination at each region of the model was calculated by use of specific geometric relationships. To verify those calculations, we analyzed a video simulation for the effects of different illumination conditions and their contributing elements. Intensity values were calculated from the relative reflectivity data determined from the video signals. The illumination values at the points along the line at the meridian of the cylinder were due to its reflectivity and also that of the medium. Similarly, the values of points distant from the shadow of the cylinder were due to the reflectivity of the background and the medium

  4. Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Huls, M. H.; Sams, Clarence F.

    1989-01-01

    In view of the suggestions by Chabrier et al. (1987) and Steardo and Nathanson (1987) that atrial natriuretic peptide (ANP) may play a role in the fluid homeostasis of the brain, the ANP receptors in primary cultures of bovine brain microvessel endothelian cells were quantitated and characterized. Results of partition binding studies and the effect of cGMP additions indicated the presence of at least two types of ANP receptors, with the majority of the receptors being the nonguanylate cyclase coupled receptors. The presence of at least two ANP receptor types suggests an active role for ANP in regulating brain endothelial cell function.

  5. Parent tree effects on reestablishment of Acacia koa in abandoned pasture and the influence of initial density on stand development

    Treesearch

    Paul G. Scowcroft

    2012-01-01

    Increasingly private landholders in Hawaii are considering native forest restoration for their lands, and some public agencies have already started such work. Initial efforts have focused on reestablishing Acacia koa to recover alien-grass-dominated sites. This study was done in Hakalau Forest National Wildlife Refuge, Island of Hawaii, to...

  6. An investigation of crown fuel bulk density effects on the dynamics of crown fire initiation in shrublands

    Treesearch

    Watcharapong Tachajapong; Jesse Lozano; Shankar Mahalingam; Xiangyang Zhou; David R. Weise

    2008-01-01

    Crown fire initiation is studied by using a simple experimental and detailed physical modeling based on Large Eddy Simulation (LES). Experiments conducted thus far reveal that crown fuel ignition via surface fire occurs when the crown base is within the continuous flame region and does not occur when the crown base is located in the hot plume gas region of the surface...

  7. Modifying mixing and instability growth through the adjustment of initial conditions in a high-energy-density counter-propagating shear experiment on OMEGA

    SciTech Connect

    Merritt, E. C. Doss, F. W.; Loomis, E. N.; Flippo, K. A.; Kline, J. L.

    2015-06-15

    Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k-ϵ type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varying two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. We also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths.

  8. Modifying mixing and instability growth through the adjustment of initial conditions in a high-energy-density counter-propagating shear experiment on OMEGA

    DOE PAGES

    Merritt, E. C.; Doss, F. W.; Loomis, E. N.; ...

    2015-06-24

    Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k-ϵ type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varyingmore » two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. In addition, we also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths.« less

  9. Modifying mixing and instability growth through the adjustment of initial conditions in a high-energy-density counter-propagating shear experiment on OMEGA

    SciTech Connect

    Merritt, E. C.; Doss, F. W.; Loomis, E. N.; Flippo, K. A.; Kline, J. L.

    2015-06-24

    Counter-propagating shear experiments conducted at the OMEGA Laser Facility have been evaluating the effect of target initial conditions, specifically the characteristics of a tracer foil located at the shear boundary, on Kelvin-Helmholtz instability evolution and experiment transition toward nonlinearity and turbulence in the high-energy-density (HED) regime. Experiments are focused on both identifying and uncoupling the dependence of the model initial turbulent length scale in variable-density turbulence models of k-ϵ type on competing physical instability seed lengths as well as developing a path toward fully developed turbulent HED experiments. We present results from a series of experiments controllably and independently varying two initial types of scale lengths in the experiment: the thickness and surface roughness (surface perturbation scale spectrum) of a tracer layer at the shear interface. We show that decreasing the layer thickness and increasing the surface roughness both have the ability to increase the relative mixing in the system, and thus theoretically decrease the time required to begin transitioning to turbulence in the system. In addition, we also show that we can connect a change in observed mix width growth due to increased foil surface roughness to an analytically predicted change in model initial turbulent scale lengths.

  10. Polymer-grafted nanoparticles prepared by surface-initiated polymerization: the characterization of polymer chain conformation, grafting density and polydispersity correlated to the grafting surface curvature.

    PubMed

    Xue, Yao-Hong; Zhu, You-Liang; Quan, Wei; Qu, Fu-Heng; Han, Cheng; Fan, Jing-Tao; Liu, Hong

    2013-10-07

    The polymer-grafted nanoparticles prepared by the surface-initiated polymerization induced from the spherical surface is studied by coarse-grained molecular dynamics simulations combined with the stochastic reaction model. The coupling effect of the initiator density and the grafting surface curvature is mainly investigated. The confinement degree greatly changes with the grafting surface curvature, thus the initiation efficiency, the grafted chain polydispersity, as well as the chain mass distribution show great dependence on the surface curvature. The results reveal that preparing the nanoparticle with desired size (i.e., grafting surface curvature) is crucial for control of the grafted chain polydispersity and even its dispersion in the polymer matrix. Our studies shed light on better design of grafted nanoparticles and better control of dispersion in polymer matrices for improving the performance of polymer nanocomposite materials.

  11. Acyloxyl radical pair intermediate for the initial stage of the thermal decomposition of diacyl peroxide: a density functional study

    NASA Astrophysics Data System (ADS)

    Uchimaru, Tadafumi; Hara, Ryoma; Tanabe, Kazutoshi; Fujimori, Ken

    1997-03-01

    To examine the reaction mechanism for the thermal reorganization, or more specifically the oxygen scrambling, in diacyl peroxide, we have carried out a hybrid density functional study using formyl peroxide as a model compound. The B3LYP calculations suggest that the oxygen scrambling in diacyl peroxide is most likely to occur via a σ-acyloxyl radical pair species: the competitive pathways of the [3,3]- and [1,3]-sigmatropic shifts are highly improbable. Thus, the mechanism for the thermal oxygen scrambling in diacyl peroxide should be completely different from those for the carbon counterparts of diacyl peroxide (the Cope and Claisen rearrangement).

  12. Tobacco outlet density and demographics at the tract level of analysis in Iowa: implications for environmentally based prevention initiatives.

    PubMed

    Schneider, John E; Reid, Robert J; Peterson, N Andrew; Lowe, John B; Hughey, Joseph

    2005-12-01

    This study assessed the geographic association between tobacco outlet density and three demographic correlates-income, race, and ethnicity-at the tract level of analysis for one county in the Midwestern United States. Data for residential census tracts in a Midwestern U.S. county were derived from year 2003 licenses for 474 tobacco outlets. Demographic variables were based on 2000 census data. Census tracts with lower median household income, higher percent of African American residents, and higher percent of Latinos residents had greater density of tobacco selling retail outlets. Areas characterized by lower income and disproportionately more African Americans and Latinos have greater physical access to tobacco products. Physical access to tobacco is a critical public-health issue because, given that smokers have been shown to be price sensitive, lowering access costs (e.g., reduced travel time) is likely to increase consumption. Findings also suggest the need for structural or environmental interventions, i.e., tobacco outlet zoning laws, to mitigate the health consequences associated with tobacco use in certain populations and geographic regions.

  13. Fabrication of a modular hybrid chip to mimic endothelial-lined microvessels in flow conditions

    NASA Astrophysics Data System (ADS)

    Pitingolo, Gabriele; Vecchione, Raffaele; Falanga, Andrea P.; Guarnieri, Daniela; Netti, Paolo A.

    2017-03-01

    In vitro microvessel models exploiting microfluidic channels have been developed to replicate cardiovascular flow conditions and to more closely mimic the blood vessels by traditionally using plasma or solvent evaporation bonding methods. The drawback of these methods is represented by an irreversible sealing which prevents internal accessibility as well as the reuse of the device. This paper presents a novel, simple, and low cost procedure to fabricate a modular and reusable chip with endotheliazed microvessels in a hybrid configuration based on poly(methyl methacrylate) and polydimethylsiloxane presenting a temporary magnetic bonding. In details, small magnets are embedded in the two poly(methyl methacrylate) substrates each of them carrying a thin polydimethylsiloxane layer which provides enhanced sealing during flow conditions as compared to conventional procedures and makes the microchannels circular as preferred in cell culture. Finally, an endothelial cell layer is formed by culturing brain endothelial bEnd.3 cells inside the proposed microchannels and characterized upon microchannel aperture, demonstrating the preservation of the cell layer.

  14. 3-D visualization and quantitation of microvessels in transparent human colorectal carcinoma [corrected].

    PubMed

    Liu, Yuan-An; Pan, Shien-Tung; Hou, Yung-Chi; Shen, Ming-Yin; Peng, Shih-Jung; Tang, Shiue-Cheng; Chung, Yuan-Chiang

    2013-01-01

    Microscopic analysis of tumor vasculature plays an important role in understanding the progression and malignancy of colorectal carcinoma. However, due to the geometry of blood vessels and their connections, standard microtome-based histology is limited in providing the spatial information of the vascular network with a 3-dimensional (3-D) continuum. To facilitate 3-D tissue analysis, we prepared transparent human colorectal biopsies by optical clearing for in-depth confocal microscopy with CD34 immunohistochemistry. Full-depth colons were obtained from colectomies performed for colorectal carcinoma. Specimens were prepared away from (control) and at the tumor site. Taking advantage of the transparent specimens, we acquired anatomic information up to 200 μm in depth for qualitative and quantitative analyses of the vasculature. Examples are given to illustrate: (1) the association between the tumor microstructure and vasculature in space, including the perivascular cuffs of tumor outgrowth, and (2) the difference between the 2-D and 3-D quantitation of microvessels. We also demonstrate that the optically cleared mucosa can be retrieved after 3-D microscopy to perform the standard microtome-based histology (H&E staining and immunohistochemistry) for systematic integration of the two tissue imaging methods. Overall, we established a new tumor histological approach to integrate 3-D imaging, illustration, and quantitation of human colonic microvessels in normal and cancerous specimens. This approach has significant promise to work with the standard histology to better characterize the tumor microenvironment in colorectal carcinoma.

  15. Adeno-associated virus mediated gene delivery into coronary microvessels of chronically instrumented dogs.

    PubMed

    Post, Heiner; Kajstura, Jan; Lei, Biao; Sessa, William C; Byrne, Barry; Anversa, Piero; Hintze, Thomas H; Recchia, Fabio A

    2003-10-01

    The objective of this study was to assess the potential of adeno-associated virus (AAV)-mediated gene delivery into coronary microvessels in vivo in a large animal. Ten mongrel dogs were chronically instrumented and allowed to recover for 10 days. Dogs were reanesthetized, and the aorta was constricted by a hydraulic occluder, whereby left ventricular (LV) pressure increased by 30% and left circumflex coronary artery blood flow by 50%. Recombinant AAV (serotype 2, CMV enhancer/chicken beta-actin promoter) encoding for green fluorescent protein (GFP) was injected as a bolus into the left atrium during aortic constriction at total titers of 1010 or 1012 infectious units. Dogs were followed for 2 (n = 4)or4wk(n = 6). Hemodynamics or body weight did not change. In LV tissue slices, a fluorescein-labeled antibody to GFP stained endothelial and smooth muscle cells but was absent in myocytes. To quantify transduction, slices were then stained with antibodies against alpha-smooth muscle actin or von Willebrand factor. Approximately 4% of arterioles and 2% of microvessels stained positive for anti-GFP independent from viral titer or duration. By regression analyses, the percent of vessels transfected was proportional to the increase in LV systolic pressure during occlusion. AAV is a potential vector for gene transfer into the coronary microcirculation in large animals, including perhaps humans.

  16. Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels.

    PubMed

    Zheng, Senfeng; Cao, Yanting; Zhang, Wenjian; Liu, Honglin; You, Jia; Yin, Yiqing; Lou, Jinning; Li, Chenghui

    2016-03-01

    Leukocyte transendothelial migration and sequestration are two distinct outcomes following leukocyte adhesion to endothelium during ischemia-reperfusion injury, in which platelets may play a pivotal role. In the present study, we established an in vitro hypoxia-reoxygenation model to mimic ischemia-reperfusion injury and found platelet pre-incubation significantly increased leukocyte adhesion to endothelial cells after hyoxia-reoxygenation (over 67%). Blockade of endothelial-cell-expressed adhesion molecules inhibited leukocyte direct adhesion to endothelial cells, while platelet-mediated leukocyte adhesion was suppressed by blockade of platelet-expressed adhesion molecules. Further experiments revealed platelets acted as a bridge to mediate leukocyte adhesion, and platelet-mediated adhesion was the predominant pattern in the presence of platelets. However, platelet pre-incubation significantly suppressed leukocyte transendothelial migration after hypoxia-reoxygenation (over 31%), which could be aggravated by blockade of endothelial-cell-expressed adhesion molecules, but alleviated by blockade of platelet- expressed adhesion molecules. This would indicate that platelet-mediated adhesion disrupted leukocyte transendothelial migration. An in vivo mesenteric ischemia-reperfusion model demonstrated leukocyte transfusion alone caused mild leukocyte adhesion to reperfused vessels and subsequent leukocyte infiltration, while simultaneous leukocyte and platelet transfusion led to massive leukocyte adhesion and sequestration within reperfused microvessels. Our studies revealed platelets enhanced leukocyte adhesion to endothelial cells, but suppressed leukocyte transendothelial migration. Overall, this leads to leukocyte sequestration in hypoxia-reoxygenated microvessels.

  17. A standalone perfusion platform for drug testing and target validation in micro-vessel networks.

    PubMed

    Zhang, Boyang; Peticone, Carlotta; Murthy, Shashi K; Radisic, Milica

    2013-01-01

    Studying the effects of pharmacological agents on human endothelium includes the routine use of cell monolayers cultivated in multi-well plates. This configuration fails to recapitulate the complex architecture of vascular networks in vivo and does not capture the relationship between shear stress (i.e. flow) experienced by the cells and dose of the applied pharmacological agents. Microfluidic platforms have been applied extensively to create vascular systems in vitro; however, they rely on bulky external hardware to operate, which hinders the wide application of microfluidic chips by non-microfluidic experts. Here, we have developed a standalone perfusion platform where multiple devices were perfused at a time with a single miniaturized peristaltic pump. Using the platform, multiple micro-vessel networks, that contained three levels of branching structures, were created by culturing endothelial cells within circular micro-channel networks mimicking the geometrical configuration of natural blood vessels. To demonstrate the feasibility of our platform for drug testing and validation assays, a drug induced nitric oxide assay was performed on the engineered micro-vessel network using a panel of vaso-active drugs (acetylcholine, phenylephrine, atorvastatin, and sildenafil), showing both flow and drug dose dependent responses. The interactive effects between flow and drug dose for sildenafil could not be captured by a simple straight rectangular channel coated with endothelial cells, but it was captured in a more physiological branching circular network. A monocyte adhesion assay was also demonstrated with and without stimulation by an inflammatory cytokine, tumor necrosis factor-α.

  18. Velocity measurement of microvessels using phase-contrast magnetic resonance angiography at 7 Tesla MRI.

    PubMed

    Kang, Chang-Ki; Park, Chan-A; Lee, David Soobin; Lee, Yeong-Bae; Park, Cheol-Wan; Kim, Young-Bo; Cho, Zang-Hee

    2016-04-01

    The purpose of this study was to measure the velocity and direction of blood flow in microvessels, such as lenticulostriate arteries (LSAs), using PC MRA. Eleven healthy subjects were scanned with 7 Tesla (T) MRI. Three velocity encoding (VENC) values of 15, 50, and 100 cm/s were tested for detecting the flow velocity in LSAs. The flow directions in Circle of Willis (CoW) were also examined with images obtained by the proposed method. Three subjects were also scanned with 3T MRI to determine the possibility of velocity measurement in LSAs. Difference between 3T and 7T was quantitatively analyzed in terms of signal-to-noise ratio and velocities in vessels and static tissues. In 7T MRI, use of VENC = 15 cm/s provided great visualization and velocity measurements in small and slow flowing vessels, such as the LSAs. The mean of peak velocities in LSAs was 9.61 ± 1.78 cm/s. The results obtained with low VENC also clearly depicted the directions of flow in CoW, especially in posterior communicating arteries. However, 3T MRI could not detect the velocity of blood flow in LSAs. This study demonstrated the potential for measuring the velocity and direction of blood flow in the targeted microvessels using an appropriate VENC and 7T MRI. © 2015 Wiley Periodicals, Inc.

  19. Major remodeling of brain microvessels during neonatal period in the mouse: A proteomic and transcriptomic study.

    PubMed

    Porte, Baptiste; Hardouin, Julie; Zerdoumi, Yasmine; Derambure, Céline; Hauchecorne, Michèle; Dupre, Nicolas; Obry, Antoine; Lequerre, Thierry; Bekri, Soumeya; Gonzalez, Bruno; Flaman, Jean M; Marret, Stéphane; Cosette, Pascal; Leroux, Philippe

    2017-02-01

    Preterm infants born before 29 gestation weeks incur major risk of subependymal/intracerebral/intraventricular hemorrhage. In mice, neonate brain endothelial cells are more prone than adult cells to secrete proteases under glutamate challenge, and invalidation of the Serpine 1 gene is accompanied by high brain hemorrhage risk up to five days after birth. We hypothesized that the structural and functional states of microvessels might account for age-dependent vulnerability in mice up to five days after birth and might represent a pertinent paradigm to approach the hemorrhage risk window observed in extreme preterms. Mass spectrometry proteome analyses of forebrain microvessels at days 5, 10 and in adult mice revealed 899 proteins and 36 enriched pathways. Microarray transcriptomic study identified 5873 genes undergoing at least two-fold change between ages and 93 enriched pathways. Both approaches pointed towards extracellular matrix, cell adhesion and junction pathways, indicating delayed microvascular strengthening after P5. Furthermore, glutamate receptors, proteases and their inhibitors exhibited convergent evolutions towards excitatory aminoacid sensitivity and low proteolytic control likely accounting for vascular vulnerability in P5 mice. Thus, age vascular specificities must be considered in future therapeutic interventions in preterms. Data are available on ProteomeXchange (identifier PXD001718) and NCBI Gene-Expression-Omnibus repository (identification GSE67870).

  20. Magnetic targeting in the impermeable microvessel with two-phase fluid model--non-Newtonian characteristics of blood.

    PubMed

    Shaw, Sachin; Murthy, P V S N

    2010-09-01

    The present investigation deals with finding the trajectories of the drug dosed magnetic carrier particle in a microvessel with two-phase fluid model which is subjected to the external magnetic field. The radius of the microvessel is divided into the endothelial glycocalyx layer in which the blood is assumed to obey Newtonian character and a core and plug regions where the blood obeys the non-Newtonian Herschel-Bulkley character which is suitable for the microvessel of radius 50 microm. The carrier particles, bound with nanoparticles and drug molecules are injected into the vascular system upstream from malignant tissue, and captured at the tumor site using a local applied magnetic field. The applied magnetic field is produced by a cylindrical magnet positioned outside the body and near the tumor position. The expressions for the fluidic force for the carrier particle traversing in the two-phase fluid in the microvessel and the magnetic force due to the external magnetic field are obtained. Several factors that influence the magnetic targeting of the carrier particles in the microvasculature, such as the size of the carrier particle, the volume fraction of embedded magnetic nanoparticles, and the distance of separation of the magnet from the axis of the microvessel are considered in the present problem. An algorithm is given to solve the system of coupled equations for trajectories of the carrier particle in the invasive case. The trajectories of the carrier particle are found for both invasive and noninvasive targeting systems. A comparison is made between the trajectories in these cases. Also, the present results are compared with the data available for the impermeable microvessel with single-phase fluid flow. Also, a prediction of the capture of therapeutic magnetic nanoparticle in the impermeable microvasculature is made for different radii, distances and volume fractions in both the invasive and noninvasive cases.

  1. Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

    NASA Astrophysics Data System (ADS)

    Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

    1995-07-01

    Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

  2. Effect of wall compliance and permeability on blood-flow rate in counter-current microvessels formed from anastomosis during tumor-induced angiogenesis.

    PubMed

    Guo, Peng; Fu, Bingmei M

    2012-04-01

    Tumor blood-flow is inhomogeneous because of heterogeneity in tumor vasculature, vessel-wall leakiness, and compliance. Experimental studies have shown that normalization of tumor vasculature by antiangiogenic therapy can improve tumor microcirculation and enhance the delivery of therapeutic agents to tumors. To elucidate the quantitative relationship between the vessel-wall compliance and permeability and the blood-flow rate in the microvessels of the tumor tissue, the tumor tissue with the normalized vasculature, and the normal tissue, we developed a transport model to simultaneously predict the interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and the blood-flow rate in a counter-current microvessel loop, which occurs from anastomosis in tumor-induced angiogenesis during tumor growth. Our model predicts that although the vessel-wall leakiness greatly affects the IFP and IFV, it has a negligible effect on the intravascular driving force (pressure gradient) for both rigid and compliant vessels, and thus a negligible effect on the blood-flow rate if the vessel wall is rigid. In contrast, the wall compliance contributes moderately to the IFP and IFV, but significantly to the vessel radius and to the blood-flow rate. However, the combined effects of vessel leakiness and compliance can increase IFP, which leads to a partial collapse in the blood vessels and an increase in the flow resistance. Furthermore, our model predictions speculate a new approach for enhancing drug delivery to tumor by modulating the vessel-wall compliance in addition to reducing the vessel-wall leakiness and normalizing the vessel density.

  3. Comparative study of 3D reconstruction of rat sciatic nerve microvessels using Evans blue and lead oxide.

    PubMed

    Zhu, Zhaowei; He, Bo; Mao, Yihua; Zhao, Lina; Zhou, Xiang; Zhu, Qingtang; Zhu, Jiakai; Tang, Maolin; Liu, Xiaolin

    2014-11-01

    The blood supply of peripheral nerve grafts is one of the important factors that affect nerve regeneration. Many investigators have studied how intraneural microvessels are distributed and ways to promote the angiogenesis of grafts. However, there still does not exist an ideal intraneural microvascular model. The purpose of this study was to compare the three-dimensional (3D) reconstruction of microvessels of the sciatic nerve in Sprague-Dawley (SD) rats after systemic perfusion with Evans blue (EB) or lead oxide. Ten adult SD rats were randomized to a fluorography group (EB) or radiography group (lead oxide). After administration of the perfusion agents, imaging information was obtained by fluorescence microscopy and micro-computed tomography (μCT). Three-dimensional reconstruction was performed, and the diameter of microvessels at a constant distance (a cross-section was taken every 1 mm), the vascular index, and volume were measured. Two-dimensional (2D) images were obtained by serial sectioning and μCT scanning using the two methods described. In the EB group, the diameter, vascular area, and vascular index of microvessels were 11.79 ± 7.23 μm, 0.14 ± 0.05 mm2, and 24.19 ± 5.03%, respectively, and in the lead oxide group 26.45 ± 11.81 μm, 0.06 ± 0.02 mm2, and 10.73 ± 2.06%, respectively. Microvessels with diameters <20 μm were visualized better in the EB group than in the lead oxide group (P < 0.01). However, there was no significant difference between the groups in the visualization of microvessels with diameters 20-49 μm (P > 0.05). Both EB and lead oxide can be used for 2D study of intraneural microvessels and 3D observation after reconstruction. Lead oxide is easy to use, and though its resolution is lower than that of EB for smaller microvessels with diameters <20 μm, it is more suitable for studying a large sample volume.

  4. High energy emission of GRB 130821A: Constraining the density profile of the circum-burst medium as well as the initial Lorentz factor of the outflow

    SciTech Connect

    Liang, Yun-Feng; Zhou, Bei; He, Hao-Ning; Fan, Yi-Zhong; Wei, Da-Ming; Tam, Pak-Hin Thomas

    2014-02-01

    GRB 130821A was detected by Fermi-GBM/LAT, Konus-WIND, SPI-ACS/INTEGRAL, RHESSI and Mars Odyssey-HEND. Although the data of GRB 130821A are very limited, we show in this work that the high energy γ-ray emission (i.e., above 100 MeV) alone imposes tight constraint on the density profile of the circum-burst medium as well as the initial Lorentz factor of the outflow. The temporal behavior of the high energy γ-ray emission is consistent with the forward shock synchrotron radiation model, and the circum-burst medium likely has a constant-density profile. The Lorentz factor is about a few hundred, similar to other bright GRBs.

  5. Quenched dynamics in interacting one-dimensional systems: Appearance of current-carrying steady states from initial domain wall density profiles

    NASA Astrophysics Data System (ADS)

    Lancaster, Jarrett; Gull, Emanuel; Mitra, Aditi

    2010-12-01

    We investigate dynamics arising after an interaction quench in the quantum sine-Gordon model for a one-dimensional system initially prepared in a spatially inhomogeneous domain wall state. We study the time evolution of the density, current, and equal time correlation functions using the truncated Wigner approximation to which quantum corrections are added in order to set the limits on its validity. For weak to moderate strengths of the backscattering interaction, the domain wall spreads out ballistically with the system within the light cone reaching a nonequilibrium steady state characterized by a net current flow. A steady-state current exists for a quench at the exactly solvable Luther-Emery point. The magnitude of the current decreases with increasing strength of the backscattering interaction. The two-point correlation function of the variable canonically conjugate to the density reaches a spatially oscillating steady state at a wavelength inversely related to the current.

  6. Radiation initiated graft copolymerization of N-vinylpyrrolidone and acrylamide onto low density polyethylene films by individual and binary system

    NASA Astrophysics Data System (ADS)

    Taher, N. H.; Dessuoki, A. M.; El-Arnaouty, M. B.

    1998-10-01

    A study has been made for the preparation of membranes by the direct radiation grafting of N-vinyl pyrrolidone (NVP), acrylamide (AAm) and its comonomer onto low density polyethylene (LDPE) films. The factors affecting the grafting process such as solvent, inhibitor, radiation dose, dose rate, monomer and comonomer concentrations on the grafting yield were studied. Dioxane was chosen as a diluent and the addition of any inhibitor failed in this grafting system. The optimum comonomer composition at which the highest grafting yield was obtained, was found to be (20/80 wt% of AAm/NVP) comonomer. The dependence of the grafting rate upon NVP, AAm and its comonomer concentration for comonomer composition (50/50 and 20/80 AAm/NVP) was found to be 1.7, 1.44, 1.9 and 1.7 order, respectively. Some selective properties of the graft copolymers such as, swelling behaviour, electrical and mechanical properties were investigated. On the other hand, the thermal stability of these membranes was measured by using differential scanning calorimetry (DSC). An improvement of these properties was observed which makes possible the use of these membranes in some practical applications such as the removal of some heavy metals from waste water.

  7. Sensitivity of mesoscale-model forecast skill to some initial-data characteristics, data density, data position, analysis procedure and measurement error

    NASA Technical Reports Server (NTRS)

    Warner, Thomas T.; Key, Lawrence E.; Lario, Annette M.

    1989-01-01

    The effects of horizontal and vertical data resolution, data density, data location, different objective analysis algorithms, and measurement error on mesoscale-forecast accuracy are studied with observing-system simulation experiments. Domain-averaged errors are shown to generally decrease with time. It is found that the vertical distribution of error growth depends on the initial vertical distribution of the error itself. Larger gravity-inertia wave noise is produced in forecasts with coarser vertical data resolution. The use of a low vertical resolution observing system with three data levels leads to more forecast errors than moderate and high vertical resolution observing systems with 8 and 14 data levels. Also, with poor vertical resolution in soundings, the initial and forecast errors are not affected by the horizontal data resolution.

  8. Visfatin Impairs Endothelium-Dependent Relaxation in Rat and Human Mesenteric Microvessels through Nicotinamide Phosphoribosyltransferase Activity

    PubMed Central

    Angulo, Javier; Villalobos, Laura A.; Cercas, Elena; Leivas, Alejandra; Bermejo, Elena; Carraro, Raffaele; Sánchez-Ferrer, Carlos F.; Peiró, Concepción

    2011-01-01

    Visfatin, also known as extracellular pre–B-cell colony–enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 µmol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 µmol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 µmol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 µmol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 µmol/L), but not an insulin receptor-blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh-induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 µmol/L) was equally impaired by

  9. BANYAN. IX. The Initial Mass Function and Planetary-mass Object Space Density of the TW HYA Association

    NASA Astrophysics Data System (ADS)

    Gagné, Jonathan; Faherty, Jacqueline K.; Mamajek, Eric E.; Malo, Lison; Doyon, René; Filippazzo, Joseph C.; Weinberger, Alycia J.; Donaldson, Jessica K.; Lépine, Sébastien; Lafrenière, David; Artigau, Étienne; Burgasser, Adam J.; Looper, Dagny; Boucher, Anne; Beletsky, Yuri; Camnasio, Sara; Brunette, Charles; Arboit, Geneviève

    2017-02-01

    A determination of the initial mass function (IMF) of the current, incomplete census of the 10 Myr-old TW Hya association (TWA) is presented. This census is built from a literature compilation supplemented with new spectra and 17 new radial velocities from ongoing membership surveys, as well as a reanalysis of Hipparcos data that confirmed HR 4334 (A2 Vn) as a member. Although the dominant uncertainty in the IMF remains census incompleteness, a detailed statistical treatment is carried out to make the IMF determination independent of binning while accounting for small number statistics. The currently known high-likelihood members are fitted by a log-normal distribution with a central mass of {0.21}-0.06+0.11 M ⊙ and a characteristic width of {0.8}-0.1+0.2 dex in the 12 M Jup-2 M ⊙ range, whereas a Salpeter power law with α ={2.2}-0.5+1.1 best describes the IMF slope in the 0.1-2 M ⊙ range. This characteristic width is higher than other young associations, which may be due to incompleteness in the current census of low-mass TWA stars. A tentative overpopulation of isolated planetary-mass members similar to 2MASS J11472421-2040204 and 2MASS J11193254-1137466 is identified: this indicates that there might be as many as {10}-5+13 similar members of TWA with hot-start model-dependent masses estimated at ˜5-7 M Jup, most of which would be too faint to be detected in 2MASS. Our new radial velocity measurements corroborate the membership of 2MASS J11472421-2040204, and secure TWA 28 (M8.5 γ), TWA 29 (M9.5 γ), and TWA 33 (M4.5 e) as members. The discovery of 2MASS J09553336-0208403, a young L7-type interloper unrelated to TWA, is also presented.

  10. LASER BIOLOGY AND MEDICINE: Recording of lymph flow dynamics in microvessels using correlation properties of scattered coherent radiation

    NASA Astrophysics Data System (ADS)

    Fedosov, I. V.; Tuchin, Valerii V.; Galanzha, E. I.; Solov'eva, A. V.; Stepanova, T. V.

    2002-11-01

    The direction-sensitive method of microflow velocity measurements based on the space — time correlation properties of the dynamic speckle field is described and used for in vivo monitoring of lymph flow in the vessels of rat mesentery. The results of measurements are compared with the data obtained from functional video microscopy of the microvessel region.

  11. Permeability and stress-jump effects on magnetic drug targeting in a permeable microvessel using Darcy model

    NASA Astrophysics Data System (ADS)

    Shaw, S.; Sutradhar, A.; Murthy, PVSN

    2017-05-01

    In the present paper, we investigated the influence of permeability of the carrier particle and stress jump condition on the porous spherical surface in magnetic drug targeting through a permeable microvessel. The nature of blood is defined by non-Newtonian Casson fluid in the core region of the microvessel and Newtonian fluid in the peripheral region which is located near the surface of the wall of the microvessel. The magnetic particles are considered as spherical and in nanosize, embedded in the carrier particle along with drug particles. A magnet is placed near the tumor position to generate a magnetic field. The relative motion of the carrier particle is the resultant of the fluidic force, magnetic force and Saffman drag force which are calculated for the spherical carrier particle. Trajectories of the carrier particle along the radial and axial direction are calculated. Effect of different parameters such as stress-jump constant, permeability of the carrier particle, pressure gradient, yield stress, Saffman force, volume fraction of the embedded magnetic nanoparticles, permeability of the microvessel wall, and the radius of the carrier particle on the trajectory of the carrier particle are discussed and displayed graphically.

  12. Application of image restoration and three-dimensional visualization techniques to frog microvessels in-situ loaded with fluorescent indicators

    NASA Astrophysics Data System (ADS)

    Pagakis, Stamatis N.; Curry, Fitz-Roy E.; Lenz, Joyce F.

    1993-07-01

    In situ experiments on microvessels require image sensors of wide dynamic range due to large variations of the intensity in the scene, and 3D visualization due to the thickness of the preparation. The images require restoration because of the inherent tissue movement, out-of- focus-light contamination, and blur. To resolve the above problems, we developed an imaging system for quantitative imaging based on a 12 bits/pixel cooled CCD camera and a PC based digital imaging system. We applied the optical sectioning technique with image restoration using a modified nearest neighbor algorithm and iterative constrained deconvolution on each of the 2D optical sections. For the 3D visualization of the data, a volume rendering software was used. The data provided 3D images of the distribution of fluorescent indicators in intact microvessels. Optical cross sections were also compared with cross sections of the same microvessels examined in the electron microscope after their luminal surfaces were labeled with a tracer which was both electron dense and fluorescent. This procedure enabled precise identification of the endothelial cells in the microvessel wall as the principal site of accumulation of the fluorescent calcium indicator, fura-2, during microperfusion experiments.

  13. [Relationship between the changes in ischemia/reperfusion cerebro-microvessel basement membrane injury and gelatinase system in senile rat].

    PubMed

    Li, Jian-sheng; Liu, Ke; Liu, Jing-xia; Wang, Ming-hang; Zhao, Yue-wu; Liu, Zheng-guo

    2008-11-01

    To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion (I/R) in aged rats. Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO). Rats were divided randomly into sham control and I/R groups in young rats [ischemia 3 hours (I 3 h) and reperfusion 6 hours (I/R 6 h), 12 hours (I/R 12 h), 24 hours (I/R 24 h), 3 days (I/R 3 d), 6 days (I/R 6 d)], and sham control group and I/R group in aged rats (I 3 h and I/R 6 h, I/R 12 h, I/R 24 h , I/R 3 d, I/R 6 d). The change in cerebro-cortex microvessel basement membrane structure, basement membrane type IV collagen (Col IV) and laminin (LN) contents, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression in every group were determined with immunohistochemical method and zymogram analysis. With the increase in age, Col IV and LN contents of the microvessel basement membrane were increased, and MMP-2 and MMP-9 expressions were stronger. With prolongation of I/R, the degradation of microvessel basement membrane components (Col IV and LN) was positively correlated with the duration of cerebral I/R. MMP-2 expression was increased gradually, and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently. Col IV(I 3 h, I/R 6 h , I/R 12 h), LN (I 3 h, I/R 6-24 h), MMP-2 (I 3 h, I/R 6 h-6 d) and MMP-9 (I 3 h, I/R 6-24 h) expression level in aged rats with I/R injury were higher, and TIMP-1 (I/R 24 h) expression was lower than those in young rats (P<0.05 or P<0.01). In addition, changes in MMP-2 and MMP-9 contents as determined by zymogram analysis method coincided with their immunoexpression. With the increase of age, alteration in membrane components of cerebro-microvessel basement membrane in rats is related with MMPs and TIMP. Cerebro-microvessel basement membrane injury is more serious in aged rats than that of young rats

  14. In-vivo visualization of melanoma tumor microvessels and blood flow velocity changes accompanying tumor growth

    NASA Astrophysics Data System (ADS)

    Ishida, Hiroki; Hachiga, Tadashi; Andoh, Tsugunobu; Akiguchi, Shunsuke

    2012-11-01

    We demonstrate that using micro multipoint laser Doppler velocimetry (μ-MLDV) for noninvasive in-vivo imaging of blood vessels is useful for diagnosing malignant melanomas by comparison with visual diagnosis by dermoscopy. The blood flow velocity in microvessels varied during growth of melanomas transplanted in mouse ears. Mouse ears were observed by μ-MLDV up to 16 days after transplantation. The blood flow velocity in the tumor increased with increasing time and reached maximum of 4.5 mm/s at 9 days, which is more than twice that prior to transplantation. After 12 days, when the lesion had grown to an area of 6.6 mm2, we observed the formation of new blood vessels in the tumor. Finally, when the lesion had an area of 18 mm2 after 16 days, the flow velocity in the tumor decreased to approximately 3.2 mm/s.

  15. Fabrication of PLGA microvessel scaffolds with circular microchannels using soft lithography

    NASA Astrophysics Data System (ADS)

    Wang, Gou-Jen; Hsueh, Cheng-Chih; Hsu, Shan-hui; Hung, Huey-Shan

    2007-10-01

    A simple micromolding method for fabricating PLGA (poly(lactic-co-glycolic acid)) microstructures made up of microchannels with a circular cross-section is presented. The thermal reflow technique is adopted to fabricate the semi-cylindrical photoresist master. The PLGA solution is prepared by dissolving PLGA polymer in acetone and then casting the solution onto the semi-cylindrical photoresist master to produce PLGA microstructures. Two PLGA membranes are bonded together to form microstructures consisting of circular microchannels. A microvessel scaffold suitable for tissue engineering was fabricated using the proposed method, and bovine endothelial cells were cultured into the scaffold by semi-dynamic seeding. The cell stain Calcein-AM was used to overcome the problem of the PLGA scaffolds becoming opaque, which in the past had made it difficult to effectively monitor the progress of cell seeding.

  16. Early initiation of smoking and alcohol drinking as a predictor of lower forearm bone mineral density in late adolescence: a cohort study in girls.

    PubMed

    Lucas, Raquel; Fraga, Sílvia; Ramos, Elisabete; Barros, Henrique

    2012-01-01

    Adolescence is a critical stage for bone accrual. It is also decisive for the establishment of behaviors such as smoking and alcohol drinking. To quantify the short- and long-term associations between smoking and drinking initiation and bone mineral density in adolescent girls. We used prospective data from 731 girls identified in public and private schools in Porto, Portugal. Evaluations were conducted when participants were 13 and 17 years old. Bone mineral density (BMD) was measured at the forearm by dual-energy X-ray absorptiometry and weight, height and fat-free mass were measured. Pubertal development status was estimated using menarche age. Self-administered questionnaires were used to collect data on smoking and alcohol drinking, physical exercise and calcium and vitamin D intakes. BMD in early and late adolescence was analyzed as a continuous or dichotomous (Z-score cutoff: -1.0) variable. Associations were calculated using linear or logistic regression. Over one quarter of these girls had tried smoking by 13, while 59% had drunk alcoholic beverages and 20% had experienced both behaviors by that age. Lower mean BMD at 17 years of age was observed in girls who had ever smoked by 13, as well as in those who reported drinking at that age. There were no significant cross-sectional associations between experience and frequency of smoking or drinking and BMD at 13 years of age. However, we observed significant associations between BMD z-score<-1 in late adolescence and having ever smoked by 13, after adjustment for menarche age and sports practice, (OR = 1.92; 95% CI: 1.21, 3.05) and with ever smoking and drinking in the same period (OR = 2.33; 95% CI: 1.36, 4.00). Our study adds prospective evidence to the role of early initiation of smoking and alcohol drinking as relevant markers of lower bone mineral density in late adolescence.

  17. Morphological and morphometric changes in rat optic nerve microvessels in a glaucoma experimental model.

    PubMed

    Moreno, M; Ríos, M C; Alba, C; Díaz, F; Villena, A; Figueroa-Ortiz, L C; García-Campos, J

    2014-12-01

    To study the morphological and morphometric changes produced in the capillaries of the optic nerve (ON) head and initial portion after the experimental increase in intraocular pressure (IOP). Wistar rats underwent cauterization of three episcleral veins, which produced an immediate increase in the IOP, and was maintained for 3 months. Sagittal sections of the eyeball were studied with immunohistochemical techniques, using a primary antibody to GLUT-1. The GLUT-1 positive capillaries were counted, and measurements were made of the area, perimeter and mean diameter. Microscopic examination of sections of the ON of control rats revealed a lower density and larger caliber of capillaries in the prelaminar region as compared with the other regions of the ON (P<.05). Comparison between the control and the experimental groups showed a reduction in capillary density (except in the prelaminar region) and a smaller size in all the areas of the ON studied, but less evident in the initial portion (P<.05). The increase in IOP was associated with significant qualitative and quantitative changes in the capillaries of the laminar and poslaminar regions of the ON head. These changes appear to return towards parameters compatible with normality in the initial portion of the ON, an area where the vascular collapse was less evident. These findings might explain the significant reduction in ocular blood flow seen in patients with primary open-angle glaucoma. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  18. Ontogeny of ABC and SLC transporters in the microvessels of developing rat brain.

    PubMed

    Soares, Ricardo V; Do, Tuan M; Mabondzo, Aloïse; Pons, Gérard; Chhun, Stéphanie

    2016-04-01

    The blood-brain barrier (BBB) is responsible for the control of solutes' concentration in the brain. Tight junctions and multiple ATP-binding cassette (ABC) and SoLute Carrier (SLC) efflux transporters protect brain cells from xenobiotics, therefore reducing brain exposure to intentionally administered drugs. In epilepsy, polymorphisms and overexpression of efflux transporters genes could be associated with pharmacoresistance. The ontogeny of these efflux transporters should also be addressed because their expression during development may be related to different brain exposure to antiepileptic drugs in the immature brain. We detected statistically significant higher expression of Abcb1b and Slc16a1 genes, and lower expression of Abcb1a and Abcg2 genes between the post-natal day 14 (P14) and the adult rat microvessels. P-gP efflux activity was also shown to be lower in P14 rats when compared with the adults. The P-gP proteins coded by rodent genes Abcb1a and Abcb1b are known to have different substrate affinities. The role of the Abcg2 gene is less clear in pharmacoresistance in epilepsy, nonetheless the coded protein Bcrp is frequently associated with drug resistance. Finally, we observed a higher expression of the Mct1 transporter gene in the P14 rat brain microvessels. Accordingly to our results, we suppose that age may be another factor influencing brain exposure to antiepileptics as a consequence of different expression patterns of efflux transporters between the adult and immature BBB. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  19. Effects of ageing and fitness on skin-microvessel vasodilator function in humans.

    PubMed

    Tew, Garry A; Klonizakis, Markos; Saxton, John M

    2010-05-01

    The impact of cardiopulmonary fitness (VO(2max)) on the age-related decline in skin-microvessel vasodilator function has not been fully established and the inter-relationships among different measures of microvascular vasodilator function are unknown. We used laser Doppler flowmetry to assess relative changes in forearm skin blood flow to various stimuli in three groups of adults: young (n = 15; 27 +/- 2 years), older sedentary (n = 14; 65 +/- 6 years) and older fit (n = 15; 61 +/- 5 years). Local-heating induced and post-occlusive hyperaemia responses were higher in the young and older fit groups compared to the older sedentary group (P < 0.05) and were moderately correlated with VO(2max) in the pooled cohort of older adults (r = 0.49-0.58; P < 0.05). Peak hyperaemia responses to acetylcholine and sodium nitroprusside were higher in young compared to older sedentary adults (P < 0.05) and were not associated with VO(2max) in older adults (P > 0.05). Associations among different measures of microvascular vasodilator function were generally moderate at best. In summary, the local heating and reactive hyperaemia data indicate that the age-related decline in skin-microvessel vasodilator function can be ameliorated through regular aerobic exercise training. As this is not supported by the iontophoresis data, we recommend that, when assessing microvascular function, the use of a single physiological or pharmacological stimulation coupled to laser Doppler flowmetry should be avoided. Finally, the moderate correlations between outcomes probably reflect the distinct mediators that are responsible for the vasodilator response to each test.

  20. Development of endothelial paracellular clefts and their tight junctions in the pial microvessels of the rat.

    PubMed

    Cassella, J P; Lawrenson, J G; Firth, J A

    1997-08-01

    The microvessels of the pia mater lack an investment with astrocyte processes but nonetheless have a high transendothelial electrical resistance which has caused them to be regarded as part of the blood-brain barrier. This high resistance is known to be acquired in the perinatal period. The aim of our study was to relate the known physiological changes with differentiation of the endothelial paracellular clefts and especially of their tight junctions which provide the basis for the high transendothelial resistance of blood-brain barrier vessels. Tight junctions of endothelial cell paracellular clefts in pial microvessels were examined by transmission electron microscopy using goniometric tilting to reveal and measure membrane separations at tight junctions in fetal, postnatal and adult rats. These tight junctional membrane separations narrowed over the period (E16: 6.3 nm, D1: 6.4 nm, D7: 5.4 nm) and differentiated into two groups by the adult stage: one with a membrane separation of 2.8 nm and the staining characteristics of non-brain endothelial junctions, and the other with no detectable membrane separation and the staining characteristics of blood-brain barrier endothelial junctions. This patchy and incomplete differentiation of pial tight junctions into a blood-brain barrier-like form could result either from non-uniform exposure to inductive signals or to local variation in responsiveness to such agents. Although these changes in junction organization may be related to the known increase in pial transendothelial resistance in the perinatal period, we have not yet identified any sharply defined structural change which coincides with this physiological event.

  1. Effect of Pluronic P85 on Amino Acid Transport in Bovine Brain Microvessel Endothelial Cells

    PubMed Central

    Zhang, Xiaobin; Alakhova, Daria Y.; Batrakova, Elena V.; Li, Shu; Yang, Zhihui; Li, Yili

    2008-01-01

    A synthetic amphiphilic block copolymer Pluronic P85 (P85) was shown to be among the most potent inhibitors of Pgp efflux system in the blood–brain barrier (BBB) and capable of enhancing delivery of Pgp substrates to the brain. The purpose of this work is to evaluate the effects of P85 on amino acid transport in BBB. Primary bovine brain micro-vessel endothelial cells (BBMEC) grown on membrane inserts were used as an in vitro BBB model. Expression of amino acid transporters, like large neutral amino acid transporter 1, cationic amino acid transporter 1, and small neutral amino acid transporter 1, were confirmed by reverse transcriptase polymerase chain reaction. Effects of P85 on amino acid transporters were examined using their substrates: 3H-phenylalanine, 3H-lysine, and 3H-methylaminoisobutyric acid, respectively. BBMEC permeability studies were carried out in apical (AP) to basolateral (BL) and BL to AP directions. P85 added at the AP side had little, if any, effect on AP to BL (“blood to brain”) transport for all examined amino acids in BBMEC monolayers. However, 0.1% P85 added at the BL side significantly increased the BL to AP transport of these substrates. Furthermore, the effective concentrations of P85 were also shown to induce plasma membrane depolarization and increase intracellular sodium concentration in BBMEC, which can contribute to the effects of the copolymer on the energy-dependent transport systems. All together, despite profound effects on transport system(s) at the brain side of cell monolayers, P85 had no effect on AP to BL transport of amino acids in brain microvessel endothelial cell model. PMID:18677571

  2. Autonomic nerves terminating on microvessels in the pineal organs of various submammalian vertebrates.

    PubMed

    Frank, C L; Czirok, Szabina J; Vincze, Csilla; Rácz, G; Szél, A; Vígh, B

    2005-01-01

    In earlier works we have found that in the mammalian pineal organ, a part of autonomic nerves--generally thought to mediate light information from the retina--form vasomotor endings on smooth muscle cells of vessels. We supposed that they serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. In the present work, we investigated whether peripheral nerves present in the photoreceptive pineal organs of submammalians form similar terminals on microvessels. In the cyclostome, fish, amphibian, reptile and bird species investigated, autonomic nerves accompany vessels entering the arachnoidal capsule and interfollicular meningeal septa of the pineal organ. The autonomic nerves do not enter the pineal tissue proper but remain in the perivasal meningeal septa isolated by basal lamina. They are composed of unmyelinated and myelinated fibers and form terminals around arterioles, veins and capillaries. The terminals contain synaptic and granular vesicles. Comparing various vertebrates, more perivasal terminals were found in reptiles and birds than in the cyclostome, fish and amphibian pineal organs. Earlier, autonomic nerves of the pineal organs were predominantly investigated in connection with the innervation of pineal tissue. The perivasal terminals found in various submammalians show that a part of the pineal autonomic fibers are vasomotoric in nature, but the vasosensor function of some fibers cannot be excluded. We suppose that the vasomotor regulation of the pineal microvessels in the photosensory submamalian pineal--like in mammals--may serve the vascular support for circadian and circannual periodic changes in the metabolic activity of the pineal tissue. The higher number of perivasal terminals in reptiles and birds may correspond to the higher metabolic activity of the tissues in more differentiated species.

  3. The role of NF-kappaB in the angiogenic response of coronary microvessel endothelial cells.

    PubMed Central

    Stoltz, R A; Abraham, N G; Laniado-Schwartzman, M

    1996-01-01

    The activation of nuclear factor (NF)-kappaB by 12(R)-hydroxyeicosatrienoic acid [12(R)-HETrE], an arachidonic acid metabolite with potent stereospecific proinflammatory and angiogenic properties, was examined and its role in the angiogenic response was determined in capillary endothelial cells derived from coronary microvessels. Electrophoretic mobility-shift assay of nuclear protein extracts from cells treated with 12(R)-HETrE demonstrated a rapid and stereospecific time- and concentration-dependent increase in the binding activity of NF-kappaB, which was inhibitable by the antioxidants N-acetylcysteine, butylated hydroxyanisole, and pyrrolidine dithiocarbamate and was partially attenuated by the protein kinase C inhibitors, staurosporine and calphostin C. Neither 12(S)-HETrE nor other related eicosanoids--e.g., 12(R)-HETE, 12(S)-HETE, and leukotriene B4--stimulated the activation of NF-kappaB relative to 12(R)-HETrE, substantiating the claim for a specific receptor-mediated mechanism. 12(R)-HETrE stimulated the formation of capillary-like cords of microvessel endothelial cells distinguishable from a control; this effect was comparable to that observed with basic fibroblast growth factor (bFGF). Inhibition of NF-kappaB activation resulted in inhibition of capillary-like formation of endothelial cells treated with 12(R)-HETrE by 80% but did not affect growth observed with bFGF. It is suggested that 12(R)-HETrE's angiogenic activity involves the activation of NF-kappaB, possibly via protein kinase C stimulation and the generation of reactive oxygen intermediates for downstream signaling. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8610127

  4. Chronic lead treatment accelerates photochemically induced platelet aggregation in cerebral microvessels of mice, in vivo

    SciTech Connect

    Al Dhaheri, A.H.; El-Sabban, F.; Fahim, M.A.

    1995-04-01

    Effects of two chronic treatment levels with lead on platelet aggregation in cerebral (pial) microcirculation of the mouse were investigated. Exposure to lead was made by subcutaneous injections for 7 days of lead acetate dissolved in 5% glucose solution, vehicle. Two doses of lead were used, a low dose of 0.1 mg/kg and a high dose of 1.0 mg/kg. Adult male mice were divided into three groups, 10 each; one group was injected with vehicle (control), another was injected with the low dose, and the third was injected with the high dose. Additional mice were used for the determination of hematological parameters and for the lead level in serum of the three groups. On the eighth day, platelet aggregation in pial microvessels of these groups of mice was carried out in vivo. Animals were anesthetized (urethane, 1-2 mg/g, ip), the trachea was intubated, and a craniotomy was performed. Platelet aggregation in pial microvessels was induced photochemically, by activation of circulating sodium fluorescein (0.1 mg/25 g, iv) with an intense mercury light. The time required for the first platelet aggregate to appear in pial arterioles was significantly shorter in the lead-treated mice than in control. This effect was in a dose-dependent manner; 113 {+-} 44 sec for low dose and 71 {+-} 18 sec for high dose vs 155 {+-} 25 sec for control, P < 0.02 and P < 0.001, respectively. Between the two lead-treated groups, the high dose significantly (P < 0.05) shortened the time to first aggregate. These data evidenced an increased susceptibility to cerebrovascular thrombosis as a result of exposure to lead. 26 refs., 4 figs., 2 tabs.

  5. Mediastinal micro-vessels clipping during lymph node dissection may contribute to reduce postoperative pleural drainage

    PubMed Central

    Yan, Shi; Wang, Xing; Lv, Chao; Phan, Kevin; Wang, Yuzhao; Wang, Jia; Yang, Yue

    2016-01-01

    Background Postoperative pleural drainage markedly influences the length of postoperative stay and financial costs of medical care. The aim of this study is to retrospectively investigate potentially predisposing factors related to pleural drainage after curative thoracic surgery and to explore the impact of mediastinal micro-vessels clipping on pleural drainage control after lymph node dissection. Methods From February 2012 to November 2013, 322 consecutive cases of operable non-small cell lung cancers (NSCLC) undergoing lobectomy and mediastinal lymph node dissection with or without application of clipping were collected. Total and daily postoperative pleural drainage were recorded. Propensity score matching (1:2) was applied to balance variables potentially impacting pleural drainage between group clip and group control. Analyses were performed to compare drainage volume, duration of chest tube and postoperative hospital stay between the two groups. Variables linked with pleural drainage in whole cohort were assessed using multivariable logistic regression analysis. Results Propensity score matching resulted in 197 patients (matched cohort). Baseline patient characteristics were matched between two groups. Group clip showed less cumulative drainage volume (P=0.020), shorter duration of chest tube (P=0.031) and postoperative hospital stay (P=0.022) compared with group control. Risk factors significantly associated with high-output drainage in multivariable logistic regression analysis were being male, age >60 years, bilobectomy/sleeve lobectomy, pleural adhesion, the application of clip applier, duration of operation ≥220 minutes and chylothorax (P<0.05). Conclusions This study suggests that mediastinal micro-vessels clipping during lymph node dissection may reduce postoperative pleural drainage and thus shorten hospital stay. PMID:27076936

  6. ELUCID—Exploring the Local Universe with the Reconstructed Initial Density Field. I. Hamiltonian Markov Chain Monte Carlo Method with Particle Mesh Dynamics

    NASA Astrophysics Data System (ADS)

    Wang, Huiyuan; Mo, H. J.; Yang, Xiaohu; Jing, Y. P.; Lin, W. P.

    2014-10-01

    Simulating the evolution of the local universe is important for studying galaxies and the intergalactic medium in a way free of cosmic variance. Here we present a method to reconstruct the initial linear density field from an input nonlinear density field, employing the Hamiltonian Markov Chain Monte Carlo (HMC) algorithm combined with Particle-mesh (PM) dynamics. The HMC+PM method is applied to cosmological simulations, and the reconstructed linear density fields are then evolved to the present day with N-body simulations. These constrained simulations accurately reproduce both the amplitudes and phases of the input simulations at various z. Using a PM model with a grid cell size of 0.75 h -1 Mpc and 40 time steps in the HMC can recover more than half of the phase information down to a scale k ~ 0.85 h Mpc-1 at high z and to k ~ 3.4 h Mpc-1 at z = 0, which represents a significant improvement over similar reconstruction models in the literature, and indicates that our model can reconstruct the formation histories of cosmic structures over a large dynamical range. Adopting PM models with higher spatial and temporal resolutions yields even better reconstructions, suggesting that our method is limited more by the availability of computer resource than by principle. Dynamic models of structure evolution adopted in many earlier investigations can induce non-Gaussianity in the reconstructed linear density field, which in turn can cause large systematic deviations in the predicted halo mass function. Such deviations are greatly reduced or absent in our reconstruction.

  7. Elucid—exploring the local universe with the reconstructed initial density field. I. Hamiltonian Markov chain Monte Carlo method with particle mesh dynamics

    SciTech Connect

    Wang, Huiyuan; Mo, H. J.; Yang, Xiaohu; Lin, W. P.; Jing, Y. P.

    2014-10-10

    Simulating the evolution of the local universe is important for studying galaxies and the intergalactic medium in a way free of cosmic variance. Here we present a method to reconstruct the initial linear density field from an input nonlinear density field, employing the Hamiltonian Markov Chain Monte Carlo (HMC) algorithm combined with Particle-mesh (PM) dynamics. The HMC+PM method is applied to cosmological simulations, and the reconstructed linear density fields are then evolved to the present day with N-body simulations. These constrained simulations accurately reproduce both the amplitudes and phases of the input simulations at various z. Using a PM model with a grid cell size of 0.75 h {sup –1} Mpc and 40 time steps in the HMC can recover more than half of the phase information down to a scale k ∼ 0.85 h Mpc{sup –1} at high z and to k ∼ 3.4 h Mpc{sup –1} at z = 0, which represents a significant improvement over similar reconstruction models in the literature, and indicates that our model can reconstruct the formation histories of cosmic structures over a large dynamical range. Adopting PM models with higher spatial and temporal resolutions yields even better reconstructions, suggesting that our method is limited more by the availability of computer resource than by principle. Dynamic models of structure evolution adopted in many earlier investigations can induce non-Gaussianity in the reconstructed linear density field, which in turn can cause large systematic deviations in the predicted halo mass function. Such deviations are greatly reduced or absent in our reconstruction.

  8. Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial.

    PubMed

    Gaffney-Stomberg, Erin; Lutz, Laura J; Rood, Jennifer C; Cable, Sonya J; Pasiakos, Stefan M; Young, Andrew J; McClung, James P

    2014-11-01

    Calcium and vitamin D are essential nutrients for bone health. Periods of activity with repetitive mechanical loading, such as military training, may result in increases in parathyroid hormone (PTH), a key regulator of Ca metabolism, and may be linked to the development of stress fractures. Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training, but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined. This randomized, double-blind, placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D (Ca+Vit D, 2000mg and 1000IU/d, respectively), delivered as 2 snack bars per day throughout 9weeks of Army initial military training (or basic combat training, BCT) on PTH, vitamin D status, and measures of bone density and strength in personnel undergoing BCT, as well as independent effects of BCT on bone parameters. A total of 156 men and 87 women enrolled in Army BCT (Fort Sill, OK; 34.7°N latitude) volunteered for this study. Anthropometric, biochemical, and dietary intake data were collected pre- and post-BCT. In addition, peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers (n=46). Consumption of supplemental Ca+Vit D increased circulating ionized Ca (group-by-time, P=0.022), maintained PTH (group-by-time, P=0.032), and increased the osteoprotegerin:RANKL ratio (group-by-time, P=0.006). Consistent with the biochemical markers, Ca+Vit D improved vBMD (group-by-time, P=0.024) at the 4% site and cortical BMC (group-by-time, P=0.028) and thickness (group-by-time, P=0.013) at the 14% site compared to placebo. These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover, such as initial military training. This trial was

  9. Model-based Characterization of the Parameters of Dissimilatory Sulfate Reduction Under the Effect of Different Initial Density of Desulfovibrio piger Vib-7 Bacterial Cells.

    PubMed

    Kushkevych, Ivan; Bolis, Marco; Bartos, Milan

    2015-01-01

    The objective of this study was to design a model of dissimilatory sulfate reduction process using the Verhulst function, with a particular focus on the kinetics of bacterial growth, sulfate and lactate consumption, and accumulation of hydrogen sulfide and acetate. The effect of the initial density (0.12±0.011, 0.25±0.024, 0.5±0.048 and 1.0±0.096 mg cells/ml of medium) of the sulfate-reducing bacteria Desulfovibrio piger Vib-7 on the growth and dissimilatory sulfate reduction was studied. The exponential growth phase of the D. piger Vib-7 was observed for 72 hours of cultivation at the (0.12 and 0.25 mg/ml) initial concentration of bacterial cells. Sulfate and lactate were consumed incompletely during this time. The increase in the initial concentration of cells to 0.5 and 1 mg/ml led to a shortening of the exponential bacterial growth phase and a shift to the stationary phase of the growth. In the case of 0.5 mg/ml seeding, the stationary growth phase was observed in the 36(th) hour of cultivation. The increase in the initial concentration of cells to 1 mg/ml led to the beginning of the stationary growth phase in 24th hours of cultivation. Under these conditions, sulfate and lactate were consumed completely in the 48th hour of cultivation. The kinetic analysis of the curves of bacterial growth and the process of dissimilatory sulfate reduction by D. piger Vib-7 was carried out.

  10. Computational analysis on the mechanical interaction between a thrombus and red blood cells: possible causes of membrane damage of red blood cells at microvessels.

    PubMed

    Kamada, Hiroki; Imai, Yohsuke; Nakamura, Masanori; Ishikawa, Takuji; Yamaguchi, Takami

    2012-12-01

    Previous studies investigating thrombus formation have not focused on the physical interaction between red blood cells (RBCs) and thrombus, although they have been speculated that some pathological conditions such as microangiopathic hemolytic anemia (MAHA) stem from interactions between RBCs and thrombi. In this study, we investigated the mechanical influence of RBCs on primary thrombi during hemostasis. We also explored the mechanics and aggravating factors of intravascular hemolysis. Computer simulations of primary thrombogenesis in the presence and the absence of RBCs demonstrated that RBCs are unlikely to affect the thrombus height and coverage, although their presence may change microvessel hemodynamics and platelet transportation to the injured wall. Our results suggest that intravascular hemolysis owing to RBC membrane damage would be promoted by three hemodynamic factors: (1) dispersibility of platelet thrombi, because more frequent spatial thrombus formation decreases the time available for an RBC to recover its shape and enforces more severe deformation; (2) platelet thrombus stiffness, because a stiffer thrombus increases the degree of RBC deformation upon collision; and (3) vessel size and hemocyte density, because a smaller vessel diameter and higher hemocyte density decrease the room for RBCs to escape as they come closer to a thrombus, thereby enhancing thrombus-RBC interactions. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  11. Emergent molecular theory of initiation of detonation: the effect of molecular and crystal structure on thermal stability of high density energy materials

    NASA Astrophysics Data System (ADS)

    Kukla, Maija; Tsyshevsky, Roman; Sharia, Onise

    The sensitivity to detonation initiation of high density energy materials along with their performance are two most important criteria for choosing the best material for explosive formulations, booster engines, detonators, etc. After numerous experimental and theoretical attempts to develop a single parameter describing sensitivity of different classes of energetic materials, one concludes that the complexity of physical and chemical explosive properties cannot be trivialized. We report here the results of our theoretical and computational studies of thermal decomposition mechanisms and kinetics of five classes of EM: pentaerythritol tetranitrate (PETN), nitramine cyclotetramethylene-tetranitramine (HMX), diamino-dinitroethene (DADNE), bis-(nitrofurazano)-furoxane (BNFF) and benchmark triamino-trinitrobenzene (TATB). Our modeling reveals how the thermal stability depends on the molecular structure of the material and how the crystal structure may additionally hinder or catalyze decomposition reactions. We will also discuss an effect of crystalline defects on sensitivity and performance of materials.

  12. A density functional theory study of phenyl formation initiated by ethynyl radical (C2H*) and ethyne (C2H2).

    PubMed

    Santiago, Romero M; Indarto, Antonius

    2008-12-01

    An ab initio computational density functional theory (DFT) was used to study the formation of the first cyclic molecule (phenyl) initiated by the ethynyl radical (C(2)H*). The study covers a competition reaction between the addition reactions of C(2)H* with ethyne (C(2)H(2)) and some molecular re-arrangement schemes. The minimum energy paths of the preferred cyclic formation route were characterized. A thorough thermochemical analysis was performed by evaluating the differences in the energy of activation (DeltaE), enthalpy (DeltaH), and Gibb's free energy (DeltaG) of the optimized stable and transition state (TS) molecules. The reaction temperatures were set to normal (T = 298 K) and combustion (T = 1,200 K) conditions.

  13. Practical aspects of using Hertzian ring crack initiation to measure surface flaw densities in glasses: influence of humidity, friction and searched areas

    NASA Astrophysics Data System (ADS)

    Tandon, Rajan; Paliwal, Bhasker; Gibson, Cory

    2013-07-01

    Ring crack initiation loads on glass, using spherical Tungsten carbide (WC) and glass (G) indenters, are measured and analysed. Our measurements demonstrate that environmental humidity plays a key role in determining the load to fracture; experiments conducted without controlling this variable cannot be used to obtain material properties. The role of friction is explicitly considered for dissimilar (WC-G) elastic contacts. For this material pair, the stresses at fracture are well described by a boundary lubrication value of friction coefficient. The fracture loads are used in a fracture-mechanics formulation to calculate crack sizes on glass surfaces. The 'searched-area' concept for dissimilar contacts is described, and used to provide crack density values for these surfaces.

  14. Initial stages of ITO/Si interface formation: In situ x-ray photoelectron spectroscopy measurements upon magnetron sputtering and atomistic modelling using density functional theory

    SciTech Connect

    Løvvik, O. M.; Diplas, S.; Ulyashin, A.; Romanyuk, A.

    2014-02-28

    Initial stages of indium tin oxide (ITO) growth on a polished Si substrate upon magnetron sputtering were studied experimentally using in-situ x-ray photoelectron spectroscopy measurements. The presence of pure indium and tin, as well as Si bonded to oxygen at the ITO/Si interface were observed. The experimental observations were compared with several atomistic models of ITO/Si interfaces. A periodic model of the ITO/Si interface was constructed, giving detailed information about the local environment at the interface. Molecular dynamics based on density functional theory was performed, showing how metal-oxygen bonds are broken on behalf of silicon-oxygen bonds. These theoretical results support and provide an explanation for the present as well as previous ex-situ and in-situ experimental observations pointing to the creation of metallic In and Sn along with the growth of SiO{sub x} at the ITO/Si interface.

  15. Coordinated regulation of nitrogen supply mode and initial cell density for energy storage compounds production with economized nitrogen utilization in a marine microalga Isochrysis zhangjiangensis.

    PubMed

    Chi, Lei; Yao, Changhong; Cao, Xupeng; Xue, Song

    2016-01-01

    Lipids and carbohydrates are main energy storage compounds (ESC) of microalgae under stressed conditions and they are potential feedstock for biofuel production. Yet, the sustainable and commercially successful production of ESC in microalgae needs to consider nitrogen utilization efficiency. Here the impact of different initial cell densities (ICDs) on ESC accumulation in Isochrysis zhangjiangensis under two nitrogen supply modes (an initially equal concentration of nitrogen per-cell in the medium (N1) and an equal total concentration of nitrogen in the culture system (N2)) were investigated. The results demonstrated that the highest ESC yield (1.36gL(-1)) at N1, which included a maximal nitrogen supply in the cultivation system, and the highest ESC content (66.5%) and ESC productivity per mass of nitrogen (3.28gg(-1) (N) day(-1)) at N2, were all obtained under a high ICD of 8.0×10(6)cellsmL(-1). Therefore I. zhangjiangensis qualifies for ESC-enriched biomass production with economized nitrogen utilization.

  16. Early Initiation of Smoking and Alcohol Drinking as a Predictor of Lower Forearm Bone Mineral Density in Late Adolescence: A Cohort Study in Girls

    PubMed Central

    Lucas, Raquel; Fraga, Sílvia; Ramos, Elisabete; Barros, Henrique

    2012-01-01

    Background Adolescence is a critical stage for bone accrual. It is also decisive for the establishment of behaviors such as smoking and alcohol drinking. Objective To quantify the short- and long-term associations between smoking and drinking initiation and bone mineral density in adolescent girls. Methods We used prospective data from 731 girls identified in public and private schools in Porto, Portugal. Evaluations were conducted when participants were 13 and 17 years old. Bone mineral density (BMD) was measured at the forearm by dual-energy X-ray absorptiometry and weight, height and fat-free mass were measured. Pubertal development status was estimated using menarche age. Self-administered questionnaires were used to collect data on smoking and alcohol drinking, physical exercise and calcium and vitamin D intakes. BMD in early and late adolescence was analyzed as a continuous or dichotomous (Z-score cutoff: −1.0) variable. Associations were calculated using linear or logistic regression. Results Over one quarter of these girls had tried smoking by 13, while 59% had drunk alcoholic beverages and 20% had experienced both behaviors by that age. Lower mean BMD at 17 years of age was observed in girls who had ever smoked by 13, as well as in those who reported drinking at that age. There were no significant cross-sectional associations between experience and frequency of smoking or drinking and BMD at 13 years of age. However, we observed significant associations between BMD z-score<−1 in late adolescence and having ever smoked by 13, after adjustment for menarche age and sports practice, (OR = 1.92; 95% CI: 1.21, 3.05) and with ever smoking and drinking in the same period (OR = 2.33; 95% CI: 1.36, 4.00). Conclusion Our study adds prospective evidence to the role of early initiation of smoking and alcohol drinking as relevant markers of lower bone mineral density in late adolescence. PMID:23094033

  17. Effects of raltegravir combined with tenofovir/emtricitabine on body shape, bone density, and lipids in African-Americans initiating HIV therapy.

    PubMed

    Young, Laura; Wohl, David A; Hyslop, William B; Lee, Yueh Z; Napravnik, Sonia; Wilkin, Aimee

    2015-10-01

    Raltegravir (RAL) plus tenofovir/emtricitabine (TDF/FTC) is a recommended initial antiretroviral regimen. A substantial proportion of persons diagnosed with HIV infection and starting antiretrovirals in the U.S. are African-American (AA); however, the effects of this regimen on metabolic parameters have largely been studied in white patients. Single-arm, open-label study of untreated AA HIV-infected patients administered RAL with TDF/FTC for 104 weeks. Changes in fasting lipids, insulin resistance, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), limb and trunk fat, and bone mineral density (BMD) were assessed at weeks 56 and 104. Thirty (85% men) participants were included. Median entry characteristics included age of 38 years, CD4 323 cells/mm3, HIV RNA level 29,245 copies/ml, and body mass index 28.1 kg/m2. At 56 and 104 weeks, significant increases in VAT, trunk fat, limb fat, and overall fat were observed. Bone mineral density decreased by 1.5% by week 104.There were no significant changes in non-HDL-cholesterol, fasting triglycerides, or insulin resistance. A median CD4 cell count increase of 318 cells/mm3 (IQR 179, 403; full range 40, 749) (P<0.001) was observed. Assuming missing=failure, 78 and 70% had HIV RNA levels<40 copies/ml at weeks 56 and 104, respectively. There were no treatment-related discontinuations and no new antiretroviral resistance mutations were detected. In this cohort of AAs, initiation of RAL with TDF/FTC was associated with significant general increases in fat. Significant changes in lipids or insulin resistance were not observed and there was a small decline in BMD. Therapy was well tolerated and effective. These results are consistent with findings of studies of initial antiretroviral therapy in racially diverse cohorts and inform treatment selection for AA patients starting therapy for HIV infection.

  18. Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

    PubMed

    Hoy, Jennifer F; Grund, Birgit; Roediger, Mollie; Schwartz, Ann V; Shepherd, John; Avihingsanon, Anchalee; Badal-Faesen, Sharlaa; de Wit, Stephane; Jacoby, Simone; La Rosa, Alberto; Pujari, Sanjay; Schechter, Mauro; White, David; Engen, Nicole Wyman; Ensrud, Kristine; Aagaard, Peer D; Carr, Andrew

    2017-09-01

    Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (-2.5% versus -1.0%; difference -1.5%, 95% confidence interval [CI] -2.2 to -0.8, p < 0.001) and spine (-1.9% versus -0.4%; difference -1.6%, 95% CI -2.2 to -1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. NCT00867048. © 2017 American Society for

  19. Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir

    PubMed Central

    Brown, Todd T.; Moser, Carlee; Currier, Judith S.; Ribaudo, Heather J.; Rothenberg, Jennifer; Kelesidis, Theodoros; Yang, Otto; Dubé, Michael P.; Murphy, Robert L.; Stein, James H.; McComsey, Grace A.

    2015-01-01

    Background. Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART initiation. Methods. We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss. Results. At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: −4.0% in the ATV/r group vs −3.6% in the DRV/r [P = .42]; hip: −3.9% in the ATV/r group vs −3.4% in the DRV/r group [P = .36]) but were greater in the combined PI arms than in the RAL arm (spine: −3.8% vs −1.8% [P < .001]; hip: −3.7% vs −2.4% [P = .005]). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4+ T-cell senescence and exhaustion (CD4+CD28−CD57+PD1+) and CD4+ T-cell activation (CD4+CD38+HLA-DR+) were associated with lumbar spine BMD loss. Conclusions. BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss. PMID:25948863

  20. Direct stimulation of limbal microvessel endothelial cell proliferation and capillary formation in vitro by a corneal-derived eicosanoid.

    PubMed Central

    Stoltz, R. A.; Conners, M. S.; Gerritsen, M. E.; Abraham, N. G.; Laniado-Schwartzman, M.

    1996-01-01

    12(R)-Hydroxyeicosatrienoic acid (12(R)-HETrE), a corneal epithelial derived inflammatory eicosanoid, elicits blood vessel growth into the avascular cornea in the classical corneal micropocket bioassay. Using an in vivo stimulated angiogenesis assay and 12(R)-HETrE as the angiogenic stimulus, we isolated a homogeneous population of rabbit limbal microvessel endothelial cells, the target for angiogenic factors in the anterior surface of ocular tissues, and analyzed the mitogenic and angiogenic potential of this eicosanoid. 12(R)-HETrE stereospecifically increased cell number by approximately 45%, an effect comparable to that of basic fibroblast growth factor (0.6 nmol/L; 10 ng/ml). This potent mitogenic response was maximal at 0.1 nmol/L. An additive effect (approximately 90% above control) on cell proliferation was observed when 12(R)-HETrE (0.1 nmol/L) and basic fibroblast growth factor (0.6 nmol/L) were added to quiescent cultures of rabbit limbal microvessel endothelial cells. We also show that 12(R)-HETrE, but not 12(S)-HETrE, induces cultured rabbit limbal microvessel endothelial cells to organize themselves as a network of branching cords reminiscent of capillaries. This effect was evident within 48 hours, maximal by 5 days of culture, and paralleled the effect observed with basic fibroblast growth factor. This study describes a novel method for testing site-directed angiogenesis in vitro and further strengthens the angiogenic properties of 12(R)-HETrE by demonstrating a direct effect on limbal microvessel endothelial cells. Images Figure 1 Figure 2 Figure 4 Figure 7 PMID:8546200

  1. Similar endothelial glycocalyx structures in microvessels from a range of mammalian tissues: evidence for a common filtering mechanism?

    PubMed

    Arkill, K P; Knupp, C; Michel, C C; Neal, C R; Qvortrup, K; Rostgaard, J; Squire, J M

    2011-09-07

    The glycocalyx or endocapillary layer on the luminal surface of microvessels has a major role in the exclusion of macromolecules from the underlying endothelial cells. Current structural evidence in the capillaries of frog mesentery indicates a regularity in the structure of the glycocalyx, with a center-to-center fiber spacing of 20 nm and a fiber width of 12 nm, which might explain the observed macromolecular filtering properties. In this study, we used electron micrographs of tissues prepared using perfusion fixation and tannic acid treatment. The digitized images were analyzed using autocorrelation to find common spacings and to establish whether similar structures, hence mechanisms, are present in the microvessel glycocalyces of a variety of mammalian tissues. Continuous glycocalyx layers in mammalian microvessels of choroid, renal tubules, glomerulus, and psoas muscle all showed similar lateral spacings at ∼19.5 nm (possibly in a quasitetragonal lattice) and longer spacings above 100 nm. Individual glycocalyx tufts above fenestrations in the first three of these tissues and also in stomach fundus and jejunum showed evidence for similar short-range structural regularity, but with more disorder. The fiber diameter was estimated as 18.8 (± 0.2) nm, but we believe this is an overestimate because of the staining method used. The implications of these findings are discussed.

  2. Endothelin-1 is elevated in Alzheimer's disease brain microvessels and is neuroprotective.

    PubMed

    Luo, Jinhua; Grammas, Paula

    2010-01-01

    The vasoactive protein endothelin-1 (ET-1) is produced by vascular endothelial cells and participates in the regulation of vascular inflammation. We have previously documented that the cerebral microvasculature is a source of inflammatory proteins and a likely contributor to the pathogenesis of Alzheimer's disease (AD). In this study, we (a) compare expression of ET-1 in brain microvessels isolated from AD and control brains; (b) determine thrombin regulation of ET-1 synthesis and release in brain endothelial cells; and (c) assess the effects of ET-1 on neuronal viability in vitro. Western blot analysis indicates a significantly higher level of ET-1 in AD vessels compared to vessels from age-matched controls. ET-1 expression and secretion are both induced by the inflammatory and neurotoxic protein thrombin. Pretreatment of neuronal cultures with ET-1 significantly increases neuronal survival when cells are challenged with oxidative stress (H2O2) or thrombin. The protective effect of ET-1 is blocked by incubation with an inhibitor of the c-Jun kinase (JNK) cascade. These data demonstrate that in the brain microvasculature dysfunctional or stressed endothelial cells express ET-1 and that this protein promotes the survival of brain neurons exposed to injury.

  3. Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria.

    PubMed

    Howland, Shanshan W; Poh, Chek Meng; Gun, Sin Yee; Claser, Carla; Malleret, Benoit; Shastri, Nilabh; Ginhoux, Florent; Grotenbreg, Gijsbert M; Rénia, Laurent

    2013-07-01

    Cerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite- and immune-mediated events. CD8(+) T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome-associated protein 50 that is conserved across rodent malaria species. Epitope-specific CD8(+) T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood-brain barrier in vivo. Such CD8(+) T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross-present parasite antigen, while non-ECM-causing parasites do not. Further, treatment with fast-acting anti-malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen-presenting cells may improve the outcome of CM patients. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

  4. Relationship between microvessel count and post-hepatectomy survival in patients with hepatocellular carcinoma

    PubMed Central

    Nanashima, Atsushi; Nakayama, Toshiyuki; Sumida, Yorihisa; Abo, Takafumi; Takeshita, Hiroaki; Shibata, Kenichirou; Hidaka, Shigekazu; Sawai, Terumitsu; Yasutake, Toru; Nagayasu, Takeshi

    2008-01-01

    AIM: To elucidate the relationship between the microvessel count (MVC) by CD34 analyzed by immunohistochemical method and prognosis in hepatocellular carcinoma (HCC) patients who underwent hepatectomy based on our preliminary study. METHODS: We examined relationships between MVC and clinicopathological factors in 128 HCC patients. The modified Japan Integrated Staging score (mJIS) was applied to examine subsets of HCC patients. RESULTS: Median MVC was 178/mm2, which was used as a cut-off value. MVC was not significantly associated with any clinicopathologic factors or postoperative recurrent rate. Lower MVC was associated with poor disease-free and overall survivals by univariate analysis (P = 0.039 and P = 0.087, respectively) and lower MVC represented an independent poor prognostic factor in disease-free survival by Cox’s multivariate analysis (risk ratio, 1.64; P = 0.024), in addition to tumor size, vascular invasion, macroscopic finding and hepatic dysfunction. Significant differences in disease-free and overall survivals by MVC were observed in HCC patients with mJIS 2 (P = 0.046 and P = 0.0014, respectively), but not in those with other scores. CONCLUSION: Tumor MVC appears to offer a useful prognostic marker of HCC patient survival, particularly in HCC patients with mJIS 2. PMID:18756600

  5. Microvessel Chaste: An Open Library for Spatial Modeling of Vascularized Tissues.

    PubMed

    Grogan, James A; Connor, Anthony J; Markelc, Bostjan; Muschel, Ruth J; Maini, Philip K; Byrne, Helen M; Pitt-Francis, Joe M

    2017-05-09

    Spatial models of vascularized tissues are widely used in computational physiology. We introduce a software library for composing multiscale, multiphysics models for applications including tumor growth, angiogenesis, osteogenesis, coronary perfusion, and oxygen delivery. Composition of such models is time consuming, with many researchers writing custom software. Recent advances in imaging have produced detailed three-dimensional (3D) datasets of vascularized tissues at the scale of individual cells. To fully exploit such data there is an increasing need for software that allows user-friendly composition of efficient, 3D models of vascularized tissues, and comparison of predictions with in vivo or in vitro experiments and alternative computational formulations. Microvessel Chaste can be used to build simulations of vessel growth and adaptation in response to mechanical and chemical stimuli; intra- and extravascular transport of nutrients, growth factors and drugs; and cell proliferation in complex 3D geometries. In addition, it can be used to develop custom software for integrating modeling with experimental data processing workflows, facilitated by a comprehensive Python interface to solvers implemented in C++. This article links to two reproducible example problems, showing how the library can be used to build simulations of tumor growth and angiogenesis with realistic vessel networks. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  6. In vivo PIV measurement of red blood cell velocity field in microvessels considering mesentery motion.

    PubMed

    Sugii, Yasuhiko; Nishio, Shigeru; Okamoto, Koji

    2002-05-01

    As endothelial cells are subject to flow shear stress, it is important to determine the detailed velocity distribution in microvessels in the study of mechanical interactions between blood and endothelium. Recently, particle image velocimetry (PIV) has been proposed as a quantitative method of measuring velocity fields instantaneously in experimental fluid mechanics. The authors have developed a highly accurate PIV technique with improved dynamic range. spatial resolution and measurement accuracy. In this paper, the proposed method was applied to images of the arteriole in the rat mesentery using an intravital microscope and high-speed digital video system. Taking the mesentery motion into account, the PIV technique was improved to measure red blood cell (RBC) velocity. Velocity distributions with spatial resolutions of 0.8 x 0.8 microm were obtained even near the wall in the centre plane of the arteriole. The arteriole velocity profile was blunt in the centre region of the vessel cross-section and sharp in the near-wall region. Typical flow features for non-Newtonian fluid were shown. Time-averaged velocity profiles in six cross sections with different diameters were compared.

  7. Measurement of a velocity field in microvessels using a high resolution PIV technique.

    PubMed

    Sugii, Yasuhiko; Nishio, Shigeru; Okamoto, Koji

    2002-10-01

    Because endothelial cells are subject to flow shear stress, it is important to determine the velocity distribution in microvessels during studies of the mechanical interactions between the blood and the endothelium. Particle image velocimetry (PIV) is a quantitative method for measuring velocity fields instantaneously in experimental fluid mechanics. The authors have developed a high-resolution PIV technique that improves the dynamic flow range, spatial resolution, and measurement accuracy. The proposed method was applied to images of the arteriole in the rat mesentery, using an intravital microscope and high-speed digital video system. Taking the mesentery motion into account, the PIV technique was improved to measure red blood cell (RBC) velocity. Velocity distributions with spatial resolutions of 0.8 3 0.8 mm were obtained even near the wall in the center plane of the arteriole. The arteriole velocity profile was blunt in the center region of the vessel cross-section and sharp in the near-wall region. Typical flow features for non-Newtonian fluid are shown.

  8. Simulated two-dimensional red blood cell motion, deformation, and partitioning in microvessel bifurcations.

    PubMed

    Barber, Jared O; Alberding, Jonathan P; Restrepo, Juan M; Secomb, Timothy W

    2008-10-01

    Movement, deformation, and partitioning of mammalian red blood cells (RBCs) in diverging microvessel bifurcations are simulated using a two-dimensional, flexible-particle model. A set of viscoelastic elements represents the RBC membrane and the cytoplasm. Motion of isolated cells is considered, neglecting cell-to-cell interactions. Center-of-mass trajectories deviate from background flow streamlines due to migration of flexible cells towards the mother vessel centerline upstream of the bifurcation and due to flow perturbations caused by cell obstruction in the neighborhood of the bifurcation. RBC partitioning in the bifurcation is predicted by determining the RBC fraction entering each branch, for a given partition of total flow and for a given upstream distribution of RBCs. Typically, RBCs preferentially enter the higher-flow branch, leading to unequal discharge hematocrits in the downstream branches. This effect is increased by migration toward the centerline but decreased by the effects of obstruction. It is stronger for flexible cells than for rigid circular particles of corresponding size, and decreases with increasing parent vessel diameter. For unequally sized daughter vessels, partitioning is asymmetric, with RBCs tending to enter the smaller vessel. Partitioning is not significantly affected by branching angles. Model predictions are consistent with previous experimental results.

  9. Simulated Two-Dimensional Red Blood Cell Motion, Deformation, and Partitioning in Microvessel Bifurcations

    PubMed Central

    Barber, Jared O.; Alberding, Jonathan P.; Restrepo, Juan M.; Secomb, Timothy W.

    2008-01-01

    Movement, deformation, and partitioning of mammalian red blood cells (RBCs) in diverging microvessel bifurcations are simulated using a two-dimensional, flexible-particle model. A set of viscoelastic elements represents the RBC membrane and the cytoplasm. Motion of isolated cells is considered, neglecting cell-to-cell interactions. Center-of-mass trajectories deviate from background flow streamlines due to migration of flexible cells towards the mother vessel centerline upstream of the bifurcation and due to flow perturbations caused by cell obstruction in the neighborhood of the bifurcation. RBC partitioning in the bifurcation is predicted by determining the RBC fraction entering each branch, for a given partition of total flow and for a given upstream distribution of RBCs. Typically, RBCs preferentially enter the higher-flow branch, leading to unequal discharge hematocrits in the downstream branches. This effect is increased by migration toward the centerline but decreased by the effects of obstruction. It is stronger for flexible cells than for rigid circular particles of corresponding size, and decreases with increasing parent vessel diameter. For unequally-sized daughter vessels, partitioning is asymmetric, with RBCs tending to enter the smaller vessel. Partitioning is not significantly affected by branching angles. Model predictions are consistent with previous experimental results. PMID:18686035

  10. The wall traction induced by flowing red blood cells in model microvessels and its potential mechanotransduction

    NASA Astrophysics Data System (ADS)

    Freund, Jonathan; Vermot, Julien

    2013-11-01

    There is evidence in early embryonic development, even well before advective oxygen transport is important, that the presence of red bloods cells per se trigger essential steps of normal vascular development. For example, showed that sequestration of blood cells early in the development of a mouse, such that the hematocrit is reduced, suppresses normal vascular network development. Vascular development also provides a model for remodeling and angiogenesis. We consider the transient stresses associated with blood cells flowing in model microvessels of comparable diameter to those at early stages of development (6 μm to 12 μm). A detailed simulation tool is used to show that passing blood cells present a significant fluctuating traction signature on the vessel wall, well above the mean stresses. This is particularly pronounced for slow flows (<= 50 μm/s) or small diameters (<= 7 μm), for which root-mean-square wall traction fluctuations can exceed their mean. These events potentially present mechanotranduction triggers that direct development or remodeling. Attenuation of such fluctuating tractions by a viscoelastic endothelial glycocalyx layer is also considered. NSF supported.

  11. High-contrast in vivo visualization of microvessels using novel FeCo/GC magnetic nanocrystals.

    PubMed

    Lee, Jin Hyung; Sherlock, Sarah P; Terashima, Masahiro; Kosuge, Hisanori; Suzuki, Yoriyasu; Goodwin, Andrew; Robinson, Joshua; Seo, Won Seok; Liu, Zhuang; Luong, Richard; McConnell, Michael V; Nishimura, Dwight G; Dai, Hongjie

    2009-12-01

    FeCo-graphitic carbon shell nanocrystals are a novel MRI contrast agent with unprecedented high per-metal-atom-basis relaxivity (r(1) = 97 mM(-1) sec(-1), r(2) = 400 mM(-1) sec(-1)) and multifunctional capabilities. While the conventional gadolinium-based contrast-enhanced angiographic magnetic MRI has proven useful for diagnosis of vascular diseases, its short circulation time and relatively low sensitivity render high-resolution MRI of morphologically small vascular structures such as those involved in collateral, arteriogenic, and angiogenic vessel formation challenging. Here, by combining FeCo-graphitic carbon shell nanocrystals with high-resolution MRI technique, we demonstrate that such microvessels down to approximately 100 mum can be monitored in high contrast and noninvasively using a conventional 1.5-T clinical MRI system, achieving a diagnostic imaging standard approximating that of the more invasive X-ray angiography. Preliminary in vitro and in vivo toxicity study results also show no sign of toxicity.

  12. Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria

    PubMed Central

    Howland, Shanshan W; Poh, Chek Meng; Gun, Sin Yee; Claser, Carla; Malleret, Benoit; Shastri, Nilabh; Ginhoux, Florent; Grotenbreg, Gijsbert M; Rénia, Laurent

    2013-01-01

    Cerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite- and immune-mediated events. CD8+ T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome-associated protein 50 that is conserved across rodent malaria species. Epitope-specific CD8+ T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood–brain barrier in vivo. Such CD8+ T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross-present parasite antigen, while non-ECM-causing parasites do not. Further, treatment with fast-acting anti-malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen-presenting cells may improve the outcome of CM patients. PMID:23681698

  13. TIGHT JUNCTION PROTEIN EXPRESSION AND BARRIER PROPERTIES OF IMMORTALIZED MOUSE BRAIN MICROVESSEL ENDOTHELIAL CELLS

    PubMed Central

    Brown, Rachel C.; Morris, Andrew P.; O’Neil, Roger G.

    2007-01-01

    Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions. PMID:17169347

  14. Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells.

    PubMed

    Brown, Rachel C; Morris, Andrew P; O'Neil, Roger G

    2007-01-26

    Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions.

  15. Evaluation of brain-targeted chitosan nanoparticles through blood-brain barrier cerebral microvessel endothelial cells.

    PubMed

    Sahin, Adem; Yoyen-Ermis, Digdem; Caban-Toktas, Secil; Horzum, Utku; Aktas, Yesim; Couvreur, Patrick; Esendagli, Gunes; Capan, Yilmaz

    2017-09-13

    The blood-brain barrier (BBB) is the major problem for the treatment of central nervous system diseases. A previous study from our group showed that the brain-targeted chitosan nanoparticles-loaded with large peptide moieties can rapidly cross the barrier and provide neuroprotection. The present study aims to determine the efficacy of the brain-targeted chitosan nanoparticles' uptake by the human BBB cerebral microvessel endothelial cells (hCMECs) and to investigate the underlying mechanisms for enhanced cellular entry. Fluorescently labelled nanoparticles either conjugated with antibodies recognising human transferrin receptor (anti-TfR mAb) or not were prepared, characterised and their interaction with cerebral endothelial cells was evaluated. The antibody decoration of chitosan nanoparticles significantly increased their entry into hCMEC/D3 cell line. Inhibition of cellular uptake by chlorpromazine indicated that the anti-TfR mAb-conjugated nanoparticles were preferentially cell internalised through receptor-mediated endocytosis pathway. Alternatively, as primarily observed with control chitosan nanoparticles, aggregation of nanoparticles may also have induced macropinocytosis.

  16. Control of in vivo microvessel ingrowth by modulation of biomaterial local architecture and chemistry

    SciTech Connect

    Sanders, Joan E.; Baker, Aaron B.; Golledge, Stephen

    2002-04-01

    We developed a method for controlling local architecture and chemistry simultaneously in biomaterial implants to control microvessel ingrowth in vivo. Porous polypropylene disks (5 mm in diameter and 40 um thick) were plasma-coated with a fluoropolymer and then laser-drilled with 50-*m-diameter holes through their thickness. We then oxidized the disks to create hydroxyl functionality on the exposed polypropylene (inside the holes). Acrylamide was grafted to the hydroxyl groups through polymerization in the presence of activating ceric ions. Staining with toluidine blue O demonstrated that grafting occurred only inside the holes. We used the Hoffman degradation reaction to convert the amide groups of acrylamide to amine groups, and then we used ethylene glycol diglycidyl ether to attach biomolecules of interest inside the holes: secreted protein acidic and rich in cysteine (SPARC) peptide Lys-Gly-His-Lys (KGHK; angiogenic), thrombospondin-2 (TSP; antiangiogenic), or albumin (rat; neutral). In vivo testing in a rat subcutaneous dorsum model for a 3-week interval demonstrated a greater vessel surface area (p = 0.032) and a greater number of vessels (p = 0.043) in tissue local to the holes with KGHKimmobilized disks than with TSP-immobilized disks. However, differences between KGHK-immobilized and albuminimmobilized disks were less significant (p = 0.120 and p = 0.289 for the vessel surface area and number of vessels, respectively). The developed methods have potential applications in biomaterial design applications for which selective neovascularization is desired.

  17. Corticosteroid receptors in cells derived from rat brain microvessels: mRNA identification and aldosterone binding.

    PubMed

    Loffreda, N; Eldin, P; Auzou, G; Frelin, C; Claire, M

    1992-01-01

    B7 is a cell clone derived from rat brain microvessels. Expression of an amiloride-sensitive cationic channel has been recently established in these cells. In this study, the polymerase chain reaction (PCR) was used to amplify definite segments of mineralocorticoid and glucocorticoid receptor mRNA in B7 cells. Aldosterone binding was also characterized. Two classes of sites were detected. Aldosterone exhibited a high affinity for type I sites [dissociation constant (Kd) approximately 0.3 nM] and a lower one for type II sites (Kd approximately 20 nM). RU 28362, a highly specific glucocorticoid agonist, did not compete for type I sites. RU 28362 and dexamethasone were better competitors for type II sites than aldosterone. The sedimentation coefficients of aldosterone type I and type II complexes were approximately 9S. These characteristics are close to the one exhibited by aldosterone type I and type II receptors in rat kidney and other target tissues. In intact B7 cells, aldosterone binding expressed as number of acceptor sites per cell was higher (approximately 41,000 for type II and 8,800 for type I) than in the soluble cellular extract (approximately 18,000 for type II and 1,000 for type I).

  18. Comparison of Retinal Microvessel Blood Flow Velocities Acquired with Two Different Fields of View.

    PubMed

    Zhou, Jin; Li, Min; Chen, Wan; Yang, Ye; Hu, Liang; Wang, Liang; Jiang, Hong; Wang, Jianhua

    2017-01-01

    To compare the different retinal blood flow velocities (BFVs) acquired with different fields of view (FOVs) using the retinal function imager (RFI), twenty eyes of twenty healthy subjects were enrolled in the study. Retinal microvessel BFV in the macula was acquired with both a wide FOV (35 degrees, 7.3 × 7.3 mm(2)) and a commonly used small FOV (20 degrees, 4.3 × 4.3 mm(2)). The 35-degree FOV was trimmed to be equivalent to the 20-degree FOV to compare the BFVs of the similar FOVs using different settings. With the 35-degree FOV, both retinal arteriolar and venular BFVs were significantly greater than the 20-degree FOV (P < 0.001). When the 20-degree FOV was compared to the trimmed equivalent 20-degree FOV acquired using the 35-degree FOV, significant BFV differences were found in both the arterioles (P = 0.029) and venules (P < 0.001). This is the first study to compare retinal blood flow velocities acquired with different FOVs using RFI. The conversion factor from 35 degrees to 20 degrees is 0.95 for arteriolar BFV and 0.92 for venular BFV, which may be used for comparing BFVs acquired with different FOVs.

  19. Comparison of Retinal Microvessel Blood Flow Velocities Acquired with Two Different Fields of View

    PubMed Central

    Zhou, Jin; Chen, Wan; Yang, Ye; Hu, Liang; Wang, Liang

    2017-01-01

    To compare the different retinal blood flow velocities (BFVs) acquired with different fields of view (FOVs) using the retinal function imager (RFI), twenty eyes of twenty healthy subjects were enrolled in the study. Retinal microvessel BFV in the macula was acquired with both a wide FOV (35 degrees, 7.3 × 7.3 mm2) and a commonly used small FOV (20 degrees, 4.3 × 4.3 mm2). The 35-degree FOV was trimmed to be equivalent to the 20-degree FOV to compare the BFVs of the similar FOVs using different settings. With the 35-degree FOV, both retinal arteriolar and venular BFVs were significantly greater than the 20-degree FOV (P < 0.001). When the 20-degree FOV was compared to the trimmed equivalent 20-degree FOV acquired using the 35-degree FOV, significant BFV differences were found in both the arterioles (P = 0.029) and venules (P < 0.001). This is the first study to compare retinal blood flow velocities acquired with different FOVs using RFI. The conversion factor from 35 degrees to 20 degrees is 0.95 for arteriolar BFV and 0.92 for venular BFV, which may be used for comparing BFVs acquired with different FOVs. PMID:28758031

  20. Dispersion characteristics of blood during nanoparticle assisted drug delivery process through a permeable microvessel.

    PubMed

    Shaw, Sachin; Ganguly, Suvankar; Sibanda, Precious; Chakraborty, Suman

    2014-03-01

    Nanoparticle assisted drug delivery holds considerable promise as a means of next generation of medicine that allows for the intravascular delivery of drugs and contrast agents. We analyze the dispersion characteristics of blood during a nanoparticle-assisted drug delivery process through a permeable microvessel. The contribution of molecular and convective diffusion is based on Taylor's theory of shear dispersion. The aggregation of red blood cells in blood flowing through small tubes (less than 40 μm) leads to the two-phase flow with a core of rouleaux surrounded by a cell-depleted peripheral layer. The core region models as a non-Newtonian Casson fluid and the peripheral region acts as a Newtonian fluid. We investigate the influence of the nanoparticle volume fraction, the permeability of the blood vessel, pressure distribution, yield stress and the radius of the nanoparticle on the effective dispersion. We show that the effective diffusion of the nanoparticles reduces with an increase in nanoparticle volume fraction. The permeability of the blood vessels increases the effective dispersion at the inlet. The present study contributes to the fundamental understanding on how the particulate nature of blood influences nanoparticle delivery, and is of particular significance in nanomedicine design for targeted drug delivery applications.

  1. High-Contrast In Vivo Visualization of Microvessels Using Novel FeCo/GC Magnetic Nanocrystals

    PubMed Central

    Lee, Jin Hyung; Sherlock, Sarah P.; Terashima, Masahiro; Kosuge, Hisanori; Suzuki, Yoriyasu; Goodwin, Andrew; Robinson, Joshua; Seo, Won Seok; Liu, Zhuang; Luong, Richard; McConnell, Michael V.; Nishimura, Dwight G.; Dai, Hongjie

    2010-01-01

    FeCo-graphitic carbon shell nanocrystals are a novel MRI contrast agent with unprecedented high per-metal-atom-basis relaxivity (r1 = 97 mM−1 sec−1, r2 = 400 mM−1 sec−1) and multifunctional capabilities. While the conventional gadolinium-based contrast-enhanced angiographic magnetic MRI has proven useful for diagnosis of vascular diseases, its short circulation time and relatively low sensitivity render high-resolution MRI of morphologically small vascular structures such as those involved in collateral, arteriogenic, and angiogenic vessel formation challenging. Here, by combining FeCo-graphitic carbon shell nanocrystals with high-resolution MRI technique, we demonstrate that such microvessels down to ~100 μm can be monitored in high contrast and noninvasively using a conventional 1.5-T clinical MRI system, achieving a diagnostic imaging standard approximating that of the more invasive X-ray angiography. Preliminary in vitro and in vivo toxicity study results also show no sign of toxicity. PMID:19859938

  2. Selective capture of endothelial and perivascular cells from brain microvessels using laser capture microdissection.

    PubMed

    Kinnecom, Katie; Pachter, Joel S

    2005-12-01

    Laser capture microdissection (LCM) of the major cell types comprising brain microvessels offers a powerful technology to explore the molecular basis of the blood-brain barrier in health and disease. However, the ability to selectively retrieve endothelial or perivascular cells, without cross-contamination from the other, has proven difficult. Additionally, histochemical methods previously described for use with LCM have not allowed for identification of all the different size branches of the microvascular tree. Here, we describe a double immunostaining method, combining bright-field and fluorescence microscopy, and using an extensive dehydration with xylene, to clearly identify and spatially resolve endothelial from perivascular cells within all size microvascular branches in frozen brain sections. LCM of these sections, coupled with RNA analysis by reverse-transcription polymerase chain reaction, revealed that captured endothelial cells show endothelial markers but no detectable markers for astrocytes or smooth muscle cells/pericytes. Conversely, captured astrocytes or smooth muscle cells/pericytes demonstrate their respective markers, but not those of endothelial cells. This approach has applicability to microarray analysis, thereby enabling global gene profiling of the different cell types along the entirety of the brain microvascular tree.

  3. Evidence for a non-universal stellar initial mass function in low-redshift high-density early-type galaxies

    NASA Astrophysics Data System (ADS)

    Dutton, Aaron A.; Mendel, J. Trevor; Simard, Luc

    2012-05-01

    We determine an absolute calibration of stellar mass-to-light ratios for the densest ≃3 per cent of early-type galaxies in the local Universe (redshift z≃ 0.08) from Sloan Digital Sky Survey (SDSS) Data Release 7. This sample of ˜4000 galaxies has, assuming a Chabrier initial mass function (IMF), effective stellar surface densities Σe > 2500 M⊙ pc-2, stellar population synthesis (SPS) stellar masses log10(MSPS/M⊙) < 10.8 and aperture velocity dispersions of ? (68 per cent range). In contrast to typical early-type galaxies, we show that these dense early-type galaxies follow the virial Fundamental Plane, which suggests that mass follows light. With the additional assumption that any dark matter does not follow the light, the dynamical masses of dense galaxies provide a direct measurement of stellar masses. Our dynamical masses (Mdyn), obtained from the spherical Jeans equations, are only weakly sensitive to the choice of anisotropy (β) due to the relatively large aperture of the SDSS fibre for these galaxies: Rap≃ 1.5Re. Assuming isotropic orbits (β= 0), we find a median log10(Mdyn/MSPS) = 0.233 ± 0.003, consistent with a Salpeter IMF, while more bottom-heavy IMFs and standard Milky Way IMFs are strongly disfavoured. Our results are consistent with, but do not require, a dependence of the IMF on dynamical mass or velocity dispersion. We find evidence for a colour dependence to the IMF such that redder galaxies have heavier IMFs with Mdyn/MSPS∝ (g-r)1.13 ± 0.09. This may reflect a more fundamental dependence of the IMF on the age or metallicity of a stellar population, or the density at which the stars formed.

  4. The Effects of Taoren-Honghua Herb Pair on Pathological Microvessel and Angiogenesis-Associated Signaling Pathway in Mice Model of CCl4-Induced Chronic Liver Disease

    PubMed Central

    Xi, Shengyan; Yue, Lifeng; Shi, Mengmeng; Peng, Ying; Xu, Yangxinzi; Wang, Xinrong; Li, Qian; Kang, Zhijun; Li, Hanjing; Wang, Yanhui

    2016-01-01

    Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR), Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways. PMID:27293456

  5. In Situ Observation of Initial Stage in Dielectric Growth and Deposition of Ultrahigh Nucleation Density Dielectric on Two-Dimensional Surfaces.

    PubMed

    Park, Jun Hong; Movva, Hema C P; Chagarov, Evgeniy; Sardashti, Kasra; Chou, Harry; Kwak, Iljo; Hu, Kai-Ting; Fullerton-Shirey, Susan K; Choudhury, Pabitra; Banerjee, Sanjay K; Kummel, Andrew C

    2015-10-14

    Several proposed beyond-CMOS devices based on two-dimensional (2D) heterostructures require the deposition of thin dielectrics between 2D layers. However, the direct deposition of dielectrics on 2D materials is challenging due to their inert surface chemistry. To deposit high-quality, thin dielectrics on 2D materials, a flat lying titanyl phthalocyanine (TiOPc) monolayer, deposited via the molecular beam epitaxy, was employed to create a seed layer for atomic layer deposition (ALD) on 2D materials, and the initial stage of growth was probed using in situ STM. ALD pulses of trimethyl aluminum (TMA) and H2O resulted in the uniform deposition of AlOx on the TiOPc/HOPG. The uniformity of the dielectric is consistent with DFT calculations showing multiple reaction sites are available on the TiOPc molecule for reaction with TMA. Capacitors prepared with 50 cycles of AlOx on TiOPc/graphene display a capacitance greater than 1000 nF/cm(2), and dual-gated devices have current densities of 10(-7)A/cm(2) with 40 cycles.

  6. Correlating Metastable-Atom Density, Reduced Electric Field, and Electron Energy Distribution in the Initiation, Transient, and Post-Transient Stages of a Pulsed Argon Discharge

    NASA Astrophysics Data System (ADS)

    Franek, James B.

    Argon emission lines, particularly those in the near-infrared region (700-900nm), are used to determine plasma properties in low-temperature, partially ionized plasmas to determine effective electron temperature [Boffard et al., 2012], and argon excited state density [Boffard et al., 2009] using appropriately assumed electron energy distributions. While the effect of radiation trapping influences the interpretation of plasma properties from emission-line ratio analysis, eliminating the need to account for these effects by directly observing the 3px-to-1sy transitions [ Boffard et al., 2012] is preferable in most cases as this simplifies the analysis. In this dissertation, a 1-Torr argon, pulsed positive column in a hollow-cathode discharge is used to study the correlation between four quantities: 420.1-419.8nm emission-line ratio, metastable-atom density, reduced electric field, and electron energy distribution. The extended coronal model is used to acquire an expression for 420.1-419.8nm emission-line ratio, which is sensitive to direct electron-impact excitation of argon excited states as well as stepwise electron-impact excitation of argon excited states for the purpose of inferring plasma quantities from experimental measurements. Initial inspection of the 420.1-419.8nm emission-line ratio suggests the pulse may be empirically divided into three distinct stages labelled the Initiation Stage, Transient Stage, and Post-Transient stage. Using equilibrium electron energy distributions from simulation to deduce excitation rates [Adams et al., 2012] in the extended coronal model affords agreement between predicted and observed metastable density in the Post-Transient stage of the discharge [Franek et al., 2015]. Applying this model-assisted diagnostic technique to the characterization of plasma systems utilizing lower-resolution spectroscopic systems is not straightforward, however, as the 419.8nm and 420.1nm emission-line profiles are convolved and become

  7. Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery.

    PubMed Central

    Kendall, S.; Towart, R.; Michel, C. C.

    1993-01-01

    1. We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately (7-mono-HR, 7,4'-di-HR, 7,3',4'-tri-HR, 5,7,3',4'-tetra-HR and 7,3'4'-tri HQ) upon the permeability of single perfused capillaries and venules in the mesenteries of pithed frogs. 2. In each experiment, the hydraulic permeability (Lp) of a single perfused microvessel and the effective osmotic pressure (sigma delta pi) exerted by macromolecules across its walls were estimated by a microcclusion technique, first during control perfusion and then in the presence of a known concentration of test substance. 3. HR, M and 7,4'-di-HR reduced Lp in a similar concentration-dependent manner over the range of 1 microgram ml-1 to 1 mg ml-1 (maximum reduction was to 40% of control Lp at 1 mg ml-1). At perfusate concentrations greater than 1 mg ml-1, these substances reduced Lp to a lesser extent. While the four other test substances reduced Lp significantly when their perfusate concentrations equalled or exceeded 100 micrograms ml-1, they were all less potent than 7,4'-di-HR. 4. The reduction in Lp induced by the mixture of flavonoids was only slightly reversed by subsequent perfusion with flavonoid-free solutions. 5. When permeability was increased by perfusing with protein-free solutions, both HR and 7,4'-di-HR reduced and then reversed the increase in Lp in a concentration-dependent manner over the range of 1 microgram ml-1 to 100 micrograms ml-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8220880

  8. Measurement of hydraulic conductivity of single perfused Rana mesenteric microvessels between periods of controlled shear stress.

    PubMed

    Neal, C R; Bates, D O

    2002-09-15

    A new method for the determination of hydraulic conductivity in individually perfused microvessels in vivo is described. A vessel is cannulated at both ends with glass micropipettes and the fluid filtration rate across the vessel wall measured from the velocities of red cells when the pressure in the micropipettes is balanced. Hydraulic conductivity measured using this double-cannulation method (2.6 (+/- 0.9) x 10(-7) cm s(-1) cmH(2)O(-1)) was not significantly different from that measured using a previously described technique in the same vessel (2.4 (+/- 0.9) x 10(-7) cm s(-1) cmH(2)O(-1) using the Landis-Michel method). Shear stress on the vessel wall was controlled by changing the difference between the inflow and outflow pressures during periods of perfusion. The volume flow through the vessel, calculated from red cell velocity either in the vessel or in the pipette, was linearly proportional to this pressure difference. Higher flow rates could only be calculated from red cell velocities in the micropipette. There was no relationship between the imposed shear stress and intervening measurements of hydraulic conductivity (r = 0.029). This novel technique has advantages over the Landis-Michel method, which include the control of outflow resistance, the measurement of shear stress under conditions of controlled pressure, the elimination of compression damage to the vessel (since vessel occlusion is not necessary) and assessment of hydraulic conductivity over the same length of vessel throughout the experiment. The measurement of solute concentrations by indwelling micropipette electrodes and the collection of perfusate for analysis are other possibilities.

  9. Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development.

    PubMed

    Grossmann, Ruth; Stence, Nick; Carr, Jenny; Fuller, Leah; Waite, Marc; Dailey, Michael E

    2002-03-01

    Some parenchymal microglia in mammalian brain tissues, termed "juxtavascular microglia," directly contact the basal lamina of blood vessels; however, the functional consequences of this unique structural relationship are unknown. Here we used a rat brain slice model of traumatic brain injury to investigate the dynamic behavior of juxtavascular microglia following activation. Juxtavascular microglia were identified by confocal 3D reconstruction in tissue slices stained with a fluorescent lectin (FITC-IB4) that labels both microglia and blood vessel endothelial cells. Immunolabeling confirmed that juxtavascular cells were true parenchymal microglia (OX42+, ED2-) and not perivascular cells or pericytes. Time-lapse imaging in live tissue slices revealed that activating juxtavascular microglia withdraw most extant branches but often maintain contact with blood vessels, usually moving to the surface of a vessel within 1-4 h. Subsequently, some microglia migrate along the parenchymal surface of vessels, moving at rates up to 40 microm/h. Activated juxtavascular microglia sometimes repeatedly extend veil-like protrusions into the surrounding tissue, consistent with a role in tissue surveillance. Juxtavascular cells were twice as likely as nonjuxtavascular cells to be locomotory by 10 h in vitro, suggesting an enhanced activation response. Moreover, 38% of all juxtavascular cells migrated along a vessel, whereas this was never observed for a nonjuxtavascular cell. These observations identify a mobile subpopulation (10%-30%) of parenchymal microglia that activate rapidly and are preferentially recruited to the surfaces of blood vessels following brain tissue injury. The dynamic and sustained interaction of microglia with brain microvessels may facilitate signaling between injured brain parenchyma and components of the blood-brain barrier or circulating immune cells of the blood in vivo. Copyright 2002 Wiley-Liss, Inc.

  10. Sexual dimorphism in the permeability response of coronary microvessels to adenosine

    PubMed Central

    Huxley, Virginia H.; Wang, JianJie; Whitt, Stevan P.

    2012-01-01

    Gender influences volume regulation via several mechanisms; whether these include microvascular exchange, especially in the heart, is not known. In response to adenosine (Ado), permeability (Ps)to protein of coronary arterioles of female pigs decreases acutely. Whether Ado induces similar Ps changes in arterioles from males or whether equivalent responses occur in coronary venules of either sex has not been determined. Hypotheses that 1) basal Ps properties and 2) Ps responses to vasoactive stimuli are sex independent were evaluated from measures of Ps to two hydrophilic proteins, α-lactalbumin and porcine serum albumin (PSA), in arterioles and venules isolated from hearts of adult male and female pigs. Consistent with hypothesis 1, basal Ps values of both microvessel types were independent of sex. Contrary to hypothesis 2, Ps responses to Ado varied with sex, protein, and vessel type. Confirming earlier studies, Ado induced a ~20% decrease in Ps to both proteins in coronary arterioles from females. In arterioles from males, Ado did not change Ps for α-lactalbumin (Psα-lactalb, 3 ± 13%) whereas Ps for PSA (PsPSA) decreased by 27 ± 8% (P < 0.005). In venules from females, Ado elevated PsPSA by 44 ± 20% (P < 0.05), whereas in those from males, Ado reduced PsPSA by 24 ± 5% (P < 0.05). The variety of outcomes is consistent with transvascular protein and protein-carried solute flux being regulated by multiple sex-dependent mechanisms in the heart and provides evidence of differences in exchange homeostasis of males and females in health and, likely, disease. PMID:15563527

  11. Measurement of hydraulic conductivity of single perfused Rana mesenteric microvessels between periods of controlled shear stress

    PubMed Central

    Neal, CR; Bates, DO

    2002-01-01

    A new method for the determination of hydraulic conductivity in individually perfused microvessels in vivo is described. A vessel is cannulated at both ends with glass micropipettes and the fluid filtration rate across the vessel wall measured from the velocities of red cells when the pressure in the micropipettes is balanced. Hydraulic conductivity measured using this double-cannulation method (2.6 (± 0.9) × 10−7 cm s−1 cmH2O−1) was not significantly different from that measured using a previously described technique in the same vessel (2.4 (± 0.9) × 10−7 cm s−1 cmH2O−1 using the Landis-Michel method). Shear stress on the vessel wall was controlled by changing the difference between the inflow and outflow pressures during periods of perfusion. The volume flow through the vessel, calculated from red cell velocity either in the vessel or in the pipette, was linearly proportional to this pressure difference. Higher flow rates could only be calculated from red cell velocities in the micropipette. There was no relationship between the imposed shear stress and intervening measurements of hydraulic conductivity (r = 0.029). This novel technique has advantages over the Landis-Michel method, which include the control of outflow resistance, the measurement of shear stress under conditions of controlled pressure, the elimination of compression damage to the vessel (since vessel occlusion is not necessary) and assessment of hydraulic conductivity over the same length of vessel throughout the experiment. The measurement of solute concentrations by indwelling micropipette electrodes and the collection of perfusate for analysis are other possibilities. PMID:12231650

  12. Low-fat, increased fruit, vegetable, and grain dietary pattern, fractures, and bone mineral density: the Women's Health Initiative Dietary Modification Trial123

    PubMed Central

    Wactawski-Wende, Jean; Wu, LieLing; Rodabough, Rebecca J; Watts, Nelson B; Tylavsky, Frances; Freeman, Ruth; Hendrix, Susan; Jackson, Rebecca

    2009-01-01

    Background: The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished. Objective: We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD). Design: Postmenopausal women (n = 48,835) aged 50–79 y (18.6% of minority race-ethnicity) were randomly assigned to receive the Dietary Modification intervention (40%, n = 19,541) (daily goal: ≤20% of energy as fat, ≥5 servings of vegetables and fruit, and ≥6 servings of grains) or to a comparison group that received no dietary changes (60%; n = 29,294). Results: After a mean 8.1 y of follow-up, 215 women in the intervention group and 285 women in the comparison group (annualized rate: 0.14% and 0.12%, respectively) experienced a hip fracture (hazard ratio: 1.12; 95% CI: 0.94, 1.34; P = 0.21). The intervention group (n = 5423; annualized rate: 3.44%) had a lower rate of reporting ≥2 falls than did the comparison group (n = 8695; annualized rate: 3.67%) (HR: 0.92; 95% CI: 0.89, 0.96; P < 0.01). There was a significant interaction according to hormone therapy use; those in the comparison group receiving hormone therapy had the lowest incidence of hip fracture. In a subset of 3951 women, hip BMD at years 3, 6, and 9 was 0.4–0.5% lower in the intervention group than in the comparison group (P = 0.003). Conclusions: A low-fat and increased fruit, vegetable, and grain diet intervention modestly reduced the risk of multiple falls and slightly lowered hip BMD but did not change the risk of osteoporotic fractures. This trial was registered at clinicaltrials.gov as NCT00000611. PMID:19403636

  13. Weight and Lean Body Mass Change with Antiretroviral Initiation and Impact on Bone Mineral Density: AIDS Clinical Trials Group Study A5224s

    PubMed Central

    Erlandson, Kristine Mace; Kitch, Douglas; Tierney, Camlin; Sax, Paul E.; Daar, Eric S.; Tebas, Pablo; Melbourne, Kathleen; Ha, Belinda; Jahed, Nasreen C.; Mccomsey, Grace A.

    2014-01-01

    Objective To compare the effect initiating different antiretroviral therapy (ART) regimens have on weight, body mass index (BMI), and lean body mass (LBM) and explore how changes in body composition are associated with bone mineral density (BMD). Methods A5224s was a substudy of A5202, a prospective trial of 1857 ART-naïve participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). All subjects underwent dual-energy absorptiometry (DXA) and abdominal CT for body composition. Analyses used 2-sample t-tests and linear regression. Results A5224s included 269 subjects: 85% male, 47% white non-Hispanic, median age 38 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 233 cells/µL. Overall, significant gains occurred in weight, BMI, and LBM at 96 weeks post randomization (all p<0.001). Assignment to ATV/r (vs EFV) resulted in significantly greater weight (mean difference 3.35 kg) and BMI gain (0.88 kg/m2; both p=0.02), but not LBM (0.67 kg; p=0.15), while ABC/3TC and TDF/FTC were not significantly different (p≥0.10). In multivariable analysis, only lower baseline CD4 count and higher HIV-1 RNA were associated with greater increase in weight, BMI, or LBM. In multivariable analyses, increased LBM was associated with an increased hip BMD. Conclusions ABC/3TC vs. TDF/FTC did not differ in change in weight, BMI, or LBM; ATV/r vs. EFV resulted in greater weight and BMI gain but not LBM. A positive association between increased LBM and increased hip BMD should be further investigated through prospective interventional studies to verify the impact of increased LBM on hip BMD. PMID:24384588

  14. Initial implementation of the conversion from the energy-subtracted CT number to electron density in tissue inhomogeneity corrections: An anthropomorphic phantom study of radiotherapy treatment planning

    SciTech Connect

    Tsukihara, Masayoshi; Noto, Yoshiyuki; Sasamoto, Ryuta; Hayakawa, Takahide; Saito, Masatoshi

    2015-03-15

    Purpose: To achieve accurate tissue inhomogeneity corrections in radiotherapy treatment planning, the authors had previously proposed a novel conversion of the energy-subtracted computed tomography (CT) number to an electron density (ΔHU–ρ{sub e} conversion), which provides a single linear relationship between ΔHU and ρ{sub e} over a wide range of ρ{sub e}. The purpose of this study is to present an initial implementation of the ΔHU–ρ{sub e} conversion method for a treatment planning system (TPS). In this paper, two example radiotherapy plans are used to evaluate the reliability of dose calculations in the ΔHU–ρ{sub e} conversion method. Methods: CT images were acquired using a clinical dual-source CT (DSCT) scanner operated in the dual-energy mode with two tube potential pairs and an additional tin (Sn) filter for the high-kV tube (80–140 kV/Sn and 100–140 kV/Sn). Single-energy CT using the same DSCT scanner was also performed at 120 kV to compare the ΔHU–ρ{sub e} conversion method with a conventional conversion from a CT number to ρ{sub e} (Hounsfield units, HU–ρ{sub e} conversion). Lookup tables for ρ{sub e} calibration were obtained from the CT image acquisitions for tissue substitutes in an electron density phantom (EDP). To investigate the beam-hardening effect on dosimetric uncertainties, two EDPs with different sizes (a body EDP and a head EDP) were used for the ρ{sub e} calibration. Each acquired lookup table was applied to two radiotherapy plans designed using the XiO TPS with the superposition algorithm for an anthropomorphic phantom. The first radiotherapy plan was for an oral cavity tumor and the second was for a lung tumor. Results: In both treatment plans, the performance of the ΔHU–ρ{sub e} conversion was superior to that of the conventional HU–ρ{sub e} conversion in terms of the reliability of dose calculations. Especially, for the oral tumor plan, which dealt with dentition and bony structures, treatment

  15. Butter feeding enhances TNF-alpha production from macrophages and lymphocyte adherence in murine small intestinal microvessels.

    PubMed

    Fujiyama, Yoichi; Hokari, Ryota; Miura, Soichiro; Watanabe, Chikako; Komoto, Shunsuke; Oyama, Tokushige; Kurihara, Chie; Nagata, Hiroshi; Hibi, Toshifumi

    2007-11-01

    Dietary fat is known to modulate immune functions. Intake of an animal fat-rich diet has been linked to increased risk of inflammation; however, little is known about how animal fat ingestion directly affects intestinal immune function. The objective of this study was to assess the effect of butter feeding on lymphocyte migration in intestinal mucosa and the changes in adhesion molecules and cytokines involved in this effect. T-lymphocytes isolated from the spleen were fluorescence-labeled and injected into recipient mice. Butter was administered into the duodenum, and villus microvessels of the small intestinal mucosa were observed under an intravital microscope. mRNA expression of adhesion molecules and cytokines in the intestinal mucosa were determined by quantitative PCR. The effect of butter feeding on tumor necrosis factor (TNF)-alpha mRNA expression of intestinal macrophages was also determined. Intraluminal butter administration significantly increased lymphocyte adherence to intestinal microvessels accompanied by increases in expression levels of adhesion molecules ICAM-1, MAdCAM-1 and VCAM-1. This accumulation was significantly attenuated by anti-MAdCAM-1 and anti-ICAM-1 antibodies. Butter administration significantly increased TNF-alpha in the lamina proprial macrophages but not interleukin-6. Anti-TNF-alpha treatment attenuated the enhanced expression of adhesion molecules induced by butter administration. T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.

  16. [Effect of taurine on the microvessel exchange function and adrenergic response of veins and arteries in the cat skeletal muscle].

    PubMed

    Kudriashov, Iu A; Denisov, P I

    2001-01-01

    In cats anesthetized with Uretan and perfused with a constant blood volume, Taurine induced responses of neither arterial nor venous vessels of the skeletal muscle but increased the capillary filtration coefficient without any significant change of the capillary pressure in the skeletal muscle's microvessels. Taurine also increased both the constrictor and the dilatory responses of the arterial and venous vessels. The mechanism of the Taurine effects upon the smooth muscle elements of arteries and veins as well as upon proper mechanisms of capillary pressure control and capillary filtration coefficient, seems to be calcium-dependent.

  17. Effects of self-reported age at nonsurgical menopause on time to first fracture and bone mineral density in the Women's Health Initiative Observational Study.

    PubMed

    Sullivan, Shannon D; Lehman, Amy; Thomas, Fridtjof; Johnson, Karen C; Jackson, Rebecca; Wactawski-Wende, Jean; Ko, Marcia; Chen, Zhao; Curb, J David; Howard, Barbara V

    2015-10-01

    Menopause is a risk factor for fracture; thus, menopause age may affect bone mass and fracture rates. We compared bone mineral density (BMD) and fracture rates among healthy postmenopausal women with varying ages at self-reported nonsurgical menopause. We compared hazard ratios for fractures and differences in BMD among 21,711 postmenopausal women from the Women's Health Initiative Observational Study cohort who had no prior hysterectomy, oophorectomy, or hormone therapy and had varying self-reported ages at menopause (<40, 40-49, or ≥50 y). Before multivariable adjustments, we found no differences in absolute fracture risk among menopause age groups. After multivariable adjustments for known risk factors for fracture, women who underwent menopause before age 40 years had a higher fracture risk at any site compared with women who underwent menopause at age 50 years or older (hazard ratio, 1.21; 95% CI, 1.02 to 1.44; P = 0.03). In a subset with BMD measurements (n = 1,351), whole-body BMD was lower in women who reported menopause before age 40 years than in women who reported menopause at ages 40 to 49 years (estimated difference, -0.034 g/cm; 95% CI, -0.07 to -0.004; P = 0.03) and women who reported menopause at age 50 years or older (estimated difference, -0.05 g/cm; 95% CI, -0.08 to -0.02; P < 0.01). Left hip BMD was lower in women who underwent menopause before age 40 years than in women who underwent menopause at age 50 years or older (estimated difference, -0.05 g/cm; 95% CI, -0.08 to -0.01; P = 0.01), and total spine BMD was lower in women who underwent menopause before age 40 years than in women who underwent menopause at age 50 years or older (estimated difference, -0.11 g/cm; 95% CI, -0.16 to -0.06; P < 0.01) and women who underwent menopause at ages 40 to 49 years (estimated difference, -0.09 g/cm; 95% CI, -0.15 to -0.04; P < 0.01). In the absence of hormone therapy, younger age at menopause may be a risk factor

  18. Role of alpha-tocopheroxyl radical in the initiation of lipid peroxidation in human low-density lipoprotein exposed to horse radish peroxidase.

    PubMed

    Witting, P K; Upston, J M; Stocker, R

    1997-02-11

    Heme-containing (per)oxidases including horse radish peroxidase (HRP)/H2O2 have been shown to oxidatively modify isolated low-density lipoprotein (LDL) in vitro and oxidized LDL is implicated in the early events leading to atherosclerosis. The role of alpha-tocopherol (alpha-TOH) in the oxidation of LDL by HRP/H2O2 is unclear, although alpha-tocopheroxyl radical (alpha-TO.), which is formed during this process, can act as a chain transfer agent of lipid peroxidation in LDL. By combining HPLC and EPR spectroscopy, we hereby show that during HRP/H2O2-induced oxidation of human LDL: (i) the accumulation of cholesteryl linoleate hydroperoxides and hydroxides (CE-O(O)H) occurs concomitantly with the formation of alpha-TO. and consumption of alpha-TOH in the absence of other detectable organic (g approximately 2) radicals; (ii) the rates of alpha-TO. formation and subsequent decay reflect the rates of both alpha-TOH consumption and CE-O(O)H accumulation; (iii) CE-O(O)H accumulation is directly dependent on the level of endogenous alpha-TOH, and vitamin E supplementation results in increased lipid oxidizability; (iv) the inhibition of HRP activity by catalase plus urate results in a persistent alpha-TO. signal, the decay (t1/2 approximately 20 min) of which is accompanied by continued accumulation of CE-O(O)H, with complete cessation of lipid peroxidation upon loss of the chromanoxyl signal. These results demonstrate a direct correlation between alpha-TOH/alpha-TO. and the extent of HRP/H2O2-induced LDL lipid peroxidation, and that this type of oxidative modification can occur in the absence of g approximately 2 radicals other than alpha-TO.. Together, the results support a role for tocopherol-mediated peroxidation but not the involvement of a protein radical in the initiation of LDL lipid peroxidation induced by HRP/H2O2.

  19. A high-density wireless underground sensor network (WUSN) to quantify hydro-ecological interactions for a UK floodplain; project background and initial results

    NASA Astrophysics Data System (ADS)

    Verhoef, A.; Choudhary, B.; Morris, P. J.; McCann, J.

    2012-04-01

    Floodplain meadows support some of the most diverse vegetation in the UK, and also perform key ecosystem services, such as flood storage and sediment retention. However, the UK now has less than 1500 ha of this unique habitat remaining. In order to conserve and better exploit the services provided by this grassland, an improved understanding of its functioning is essential. Vegetation functioning and species composition are known to be tightly correlated to the hydrological regime, and related temperature and nutrient regime, but the mechanisms controlling these relationships are not well established. The FUSE* project aims to investigate the spatiotemporal variability in vegetation functioning (e.g. photosynthesis and transpiration) and plant community composition in a floodplain meadow near Oxford, UK (Yarnton Mead), and their relationship to key soil physical variables (soil temperature and moisture content), soil nutrient levels and the water- and energy-balance. A distributed high density Wireless Underground Sensor Network (WUSN) is in the process of being established on Yarnton Mead. The majority, or ideally all, of the sensing and transmitting components will be installed below-ground because Yarnton Mead is a SSSI (Site of Special Scientific Interest, due to its unique plant community) and because occasionally sheep or cattle are grazing on it, and that could damage the nodes. This prerequisite has implications for the maximum spacing between UG nodes and their communications technologies; in terms of signal strength, path losses and requirements for battery life. The success of underground wireless communication is highly dependent on the soil type and water content. This floodplain environment is particularly challenging in this context because the soil contains a large amount of clay near the surface and is therefore less favourable to EM wave propagation than sandy soils. Furthermore, due to high relative saturation levels (as a result of high

  20. Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom.

    PubMed

    Ten Cate, David F; Luime, Jolanda J; van der Ven, Myrthe; Hazes, Johanna M W; Kooiman, Klazina; de Jong, Nico; Bosch, Johannes G

    2013-10-24

    In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom. The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine. The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes. We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used.

  1. Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom

    PubMed Central

    2013-01-01

    Introduction In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom. Methods The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine. Results The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes. Conclusions We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used. PMID:24286540

  2. Development of a direct contact astrocyte-human cerebral microvessel endothelial cells blood-brain barrier coculture model.

    PubMed

    Kulczar, Chris; Lubin, Kelsey E; Lefebvre, Sylvia; Miller, Donald W; Knipp, Gregory T

    2017-09-05

    In conventional in-vitro blood-brain barrier (BBB) models, primary and immortalized brain microvessel endothelial cell (BMEC) lines are often cultured in a monolayer or indirect coculture or triculture configurations with astrocytes or pericytes, for screening permeation of therapeutic or potentially neurotoxic compounds. In each of these cases, the physiological relevancy associated with the direct contact between the BMECs, pericytes and astrocytes that form the BBB and resulting synergistic interactions are lost. We look to overcome this limitation with a direct contact coculture model. We established and optimized a direct interaction coculture system where primary human astrocytes are cultured on the apical surface of a Transwell® filter support and then human cerebral microvessel endothelial cells (hCMEC/D3) seeded directly on the astrocyte lawn. The studies suggest the direct coculture model may provide a more restrictive and physiologically relevant model through a significant reduction in paracellular transport of model compounds in comparison with monoculture and indirect coculture. In comparison with existing methods, the indirect coculture and monoculture models utilized may limit cell-cell signaling between human astrocytes and BMECs that are possible with direct configurations. Paracellular permeability reductions with the direct coculture system may enhance therapeutic agent and potential neurotoxicant screening for BBB permeability better than the currently available monoculture and indirect coculture in-vitro models. © 2017 Royal Pharmaceutical Society.

  3. Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels.

    PubMed

    He, Tongrong; Santhanam, Anantha Vijay R; Lu, Tong; d'Uscio, Livius V; Katusic, Zvonimir S

    2017-01-01

    We tested hypothesis that activation of the prostacyclin (PGI2) receptor (IP receptor) signaling pathway in cerebral microvessels plays an important role in the metabolism of amyloid precursor protein (APP). In human brain microvascular endothelial cells activation of IP receptor with the stable analogue of PGI2, iloprost, stimulated expression of amyloid precursor protein and a disintegrin and metalloprotease 10 (ADAM10), resulting in an increased production of the neuroprotective and anticoagulant molecule, soluble APPα (sAPPα). Selective agonist of IP receptor, cicaprost, and adenylyl cyclase activator, forskolin, also enhanced expression of amyloid precursor protein and ADAM10. Notably, in cerebral microvessels of IP receptor knockout mice, protein levels of APP and ADAM10 were reduced. In addition, iloprost increased protein levels of peroxisome proliferator-activated receptor δ (PPARδ) in human brain microvascular endothelial cells. PPARδ-siRNA abolished iloprost-augmented protein expression of ADAM10. In contrast, GW501516 (a selective agonist of PPARδ) upregulated ADAM10 and increased production of sAPPα. Genetic deletion of endothelial PPARδ (ePPARδ(-/-)) in mice significantly reduced cerebral microvascular expression of ADAM10 and production of sAPPα. In vivo treatment with GW501516 increased sAPPα content in hippocampus of wild type mice but not in hippocampus of ePPARδ(-/-) mice. Our findings identified previously unrecognized role of IP-PPARδ signal transduction pathway in the production of sAPPα in cerebral microvasculature. © The Author(s) 2015.

  4. In vivo spectral and fluorescence imaging microscopy of tumor microvessel blood supply and oxygenation changes following vascular targeting agent treatment

    NASA Astrophysics Data System (ADS)

    Lee, Jennifer; Kozikowski, Raymond; Molnar, Nikolett; Siemann, Dietmar W.; Sorg, Brian S.

    2012-03-01

    The formation of new microvasculature is essential for a tumor mass to grow. Vascular targeting agents (VTAs), including anti-angiogenic drugs and vascular disrupting agents, aim to either inhibit new vasculature growth or destroy existing vasculature, respectively. Because the mechanisms for anti-angiogenic drugs and vascular disrupting agents are complementary, analysis of these drugs used together is under investigation for the enhanced treatment of tumors in comparison to each treatment alone. The preclinical evaluation of the effects of VTAs on tumor growth in small animal models is vital for the development of effective drugs for clinical use. In vivo hyperspectral imaging microscopy of hemoglobin saturation has been used previously to investigate the efficacy of VTAs through analysis of tumor microvessel oxygenation after drug administration. Combining this imaging modality with first-pass fluorescence angiographic imaging can give additional important information about the vessel morphology and blood flow changes that occur after VTA treatment, thus elucidating the relationship between microvessel structure changes and oxygenation. In this study, we report the combined use of hyperspectral and first pass fluorescence angiographic imaging to examine the relationship between vessel morphology and oxygenation of human prostate cancer tumors in mice following treatment with vascular disrupting agents, OXi4503, and anti-VEGF angiogenesis inhibitor, cediranib. Imaging of the tumors is completed before treatment as well as in the days following treatment.

  5. Initial measurements of plasma current and electron density profiles using a polarimeter/interferometer (POINT) for long pulse operation in EAST (invited).

    PubMed

    Liu, H Q; Qian, J P; Jie, Y X; Ding, W X; Brower, D L; Zou, Z Y; Li, W M; Lian, H; Wang, S X; Yang, Y; Zeng, L; Lan, T; Yao, Y; Hu, L Q; Zhang, X D; Wan, B N

    2016-11-01

    A double-pass, radially viewing, far-infrared laser-based POlarimeter-INTerferometer (POINT) system utilizing the three-wave technique has been implemented for diagnosing the plasma current and electron density profiles in the Experimental Advanced Superconducting Tokamak (EAST). POINT has been operated routinely during the most recent experimental campaign and provides continuous 11 chord line-integrated Faraday effect and density measurement throughout the entire plasma discharge for all heating schemes and all plasma conditions (including ITER relevant scenario development). Reliability of both the polarimetric and interferometric measurements is demonstrated in 25 s plasmas with H-mode and 102 s long-pulse discharges. Current density, safety factor (q), and electron density profiles are reconstructed using equilibrium fitting code (EFIT) with POINT constraints for the plasma core.

  6. Initial measurements of plasma current and electron density profiles using a polarimeter/interferometer (POINT) for long pulse operation in EAST (invited)

    NASA Astrophysics Data System (ADS)

    Liu, H. Q.; Qian, J. P.; Jie, Y. X.; Ding, W. X.; Brower, D. L.; Zou, Z. Y.; Li, W. M.; Lian, H.; Wang, S. X.; Yang, Y.; Zeng, L.; Lan, T.; Yao, Y.; Hu, L. Q.; Zhang, X. D.; Wan, B. N.

    2016-11-01

    A double-pass, radially viewing, far-infrared laser-based POlarimeter-INTerferometer (POINT) system utilizing the three-wave technique has been implemented for diagnosing the plasma current and electron density profiles in the Experimental Advanced Superconducting Tokamak (EAST). POINT has been operated routinely during the most recent experimental campaign and provides continuous 11 chord line-integrated Faraday effect and density measurement throughout the entire plasma discharge for all heating schemes and all plasma conditions (including ITER relevant scenario development). Reliability of both the polarimetric and interferometric measurements is demonstrated in 25 s plasmas with H-mode and 102 s long-pulse discharges. Current density, safety factor (q), and electron density profiles are reconstructed using equilibrium fitting code (EFIT) with POINT constraints for the plasma core.

  7. MicroRNA-155 Regulates ROS Production, NO Generation, Apoptosis and Multiple Functions of Human Brain Microvessel Endothelial Cells Under Physiological and Pathological Conditions.

    PubMed

    Liu, Yajing; Pan, Qunwen; Zhao, Yuhui; He, Caixia; Bi, Kexia; Chen, Yusen; Zhao, Bin; Chen, Yanfang; Ma, Xiaotang

    2015-12-01

    The microRNA-155 (miR155) regulates various functions of cells. Dysfunction or injury of endothelial cells (ECs) plays an important role in the pathogenesis of various vascular diseases. In this study, we investigated the role and potential mechanisms of miR155 in human brain microvessel endothelial cells (HBMECs) under physiological and pathological conditions. We detected the effects of miR155 silencing on ROS production, NO generation, apoptosis and functions of HBMECs at basal and in response to oxidized low density lipoprotein (ox-LDL). Western blot and q-PCR were used for analyzing the gene expression of epidermal growth factor receptor (EGFR)/extracellular regulated protein kinases (ERK)/p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositol-3-kinase (PI3K) and serine/threonine kinase(Akt), activated caspase-3, and intercellular adhesion molecule-1 (ICAM-1). Results showed that under both basal and challenge situations: (1) Silencing of miR155 decreased apoptosis and reactive oxygen species (ROS) production of HBMECs, whereas, promoted nitric oxide (NO) generation. (2) Silencing of miR155 increased the proliferation, migration, and tube formation ability of HBMECs, while decreased cell adhesion ability. (3) Gene expression analyses showed that EGFR/ERK/p38 MAPK and PI3K/Akt were increased and that activated caspase-3 and ICAM-1 mRNA were decreased after knockdown of miR155. In conclusion, knockdown of miR155 could modulate ROS production, NO generation, apoptosis and function of HBMECs via regulating diverse gene expression, such as caspase-3, ICAM-1 and EGFR/ERK/p38 MAPK and PI3K/Akt pathways.

  8. Effect of initial seedling size, understory competition, and overstory density on the survival and growth of Pinus echinata seedlings underplanted in hardwood forests for restoration

    Treesearch

    John M. Kabrick; Benjamin O. Knapp; Daniel C. Dey; David R. Larsen

    2015-01-01

    There is interest in restoring shortleaf pine (Pinus echinata) in pine–oak woodlands where it once was abundant. Because of its shade intolerance and slow initial growth rate, shortleaf pine restoration has remained a challenge because competition from hardwoods exhibits greater initial growth following canopy removal but greater shade tolerance with...

  9. A New Tropical Cyclone Dynamic Initialization Technique Using High Temporal and Spatial Density Atmospheric Motion Vectors and Airborne Field Campaign Data

    NASA Technical Reports Server (NTRS)

    Hendricks, Eric A.; Bell, Michael M.; Elsberry, Russell L.; Velden, Chris S.; Cecil, Dan

    2016-01-01

    Background: Initialization of tropical cyclones in numerical weather prediction (NWP) systems is a great challenge: Mass-wind ?eld balance; Secondary circulation and heating; Asymmetries. There can be large adjustments in structure and intensity in the ?rst 24 hours if the initial vortex is not in balance: Spurious gravity waves; Spin-up (model and physics). Existing mesoscale NWP model TC (Tropical Cyclone) initialization strategies: Bogus vortex, cold start from global analyses; 3DVAR or 4DVAR, possibly with synthetic observations; EnKF (Ensemble Kalman Filter); Dynamic initialization. Dynamic initialization allows vortex to have improved balance and physics spin-up at the initial time (e.g., Hendricks et al. 2013, 2011; Nguyen and Chen 2011; Fiorino and Warner 1981; Hoke and Anthes 1976). Himawari-8 geostationary satellite has capability of continuous imagery (10-minutes) over the full disk: New GOES-R satellites will have same capability. This will allow for unprecedented observations of tropical cyclones. However, current data assimila1on systems are not capable of ingesting such high temporal observations (Atmospheric Mo1on Vectors - AMVs). Hourly AMVs are produced, and thinned to 100-kilometer spacing in the horizontal. An entirely new data assimilation concept is required to utilize these observations.

  10. Velocimetry of red blood cells in microvessels by the dual-slit method: effect of velocity gradients.

    PubMed

    Roman, Sophie; Lorthois, Sylvie; Duru, Paul; Risso, Frédéric

    2012-11-01

    The dual-slit is a photometric technique used for the measurement of red blood cell (RBC) velocity in microvessels. Two photometric windows (slits) are positioned along the vessel. Because the light is modulated by the RBCs flowing through the microvessel, a time dependent signal is captured for each window. A time delay between the two signals is obtained by temporal cross correlation, and is used to deduce a velocity, knowing the distance between the two slits. Despite its wide use in the field of microvascular research, the velocity actually measured by this technique has not yet been unambiguously related to a relevant velocity scale of the flow (e.g. mean or maximal velocity) or to the blood flow rate. This is due to a lack of fundamental understanding of the measurement and also because such a relationship is crucially dependent on the non-uniform velocity distribution of RBCs in the direction parallel to the light beam, which is generally unknown. The aim of the present work is to clarify the physical significance of the velocity measured by the dual-slit technique. For that purpose, dual-slit measurements were performed on computer-generated image sequences of RBCs flowing in microvessels, which allowed all the parameters related to this technique to be precisely controlled. A parametric study determined the range of optimal parameters for the implementation of the dual-slit technique. In this range, it was shown that, whatever the parameters governing the flow, the measured velocity was the maximal RBC velocity found in the direction parallel to the light beam. This finding was then verified by working with image sequences of flowing RBCs acquired in PDMS micro-systems in vitro. Besides confirming the results and physical understanding gained from the study with computer generated images, this in vitro study showed that the profile of RBC maximal velocity across the channel was blunter than a parabolic profile, and exhibited a non-zero sliding velocity at

  11. Poly(ethylene glycol) Hydrogel Scaffolds Containing Cell-Adhesive and Protease-Sensitive Peptides Support Microvessel Formation by Endothelial Progenitor Cells

    PubMed Central

    Christoforou, Nicolas; Leong, Kam W.; Truskey, George A.; West, Jennifer L.

    2015-01-01

    The development of stable, functional microvessels remains an important obstacle to overcome for tissue engineered organs and treatment of ischemia. Endothelial progenitor cells (EPCs) are a promising cell source for vascular tissue engineering as they are readily obtainable and carry the potential to differentiate towards all endothelial phenotypes. The aim of this study was to investigate the ability of human umbilical cord blood-derived EPCs to form vessel-like structures within a tissue engineering scaffold material, a cell-adhesive and proteolytically degradable poly(ethylene glycol) (PEG) hydrogel. EPCs in co-culture with angiogenic mural cells were encapsulated in hydrogel scaffolds by mixing with polymeric precursors and using a mild photocrosslinking process to form hydrogels with homogeneously dispersed cells. EPCs formed 3D microvessels networks that were stable for at least 30 days in culture, without the need for supplemental angiogenic growth factors. These 3D EPC microvessels displayed aspects of physiological microvasculature with lumen formation, expression of endothelial cell proteins (connexin 32, VE-cadherin, eNOS), basement membrane formation with collagen IV and laminin, perivascular investment of PDGFR-β and α-SMA positive cells, and EPC quiescence (<1% proliferating cells) by 2 weeks of co-culture. Our findings demonstrate the development of a novel, reductionist system that is well-defined and reproducible for studying progenitor cell-driven microvessel formation. PMID:27042236

  12. Prediction of core level binding energies in density functional theory: Rigorous definition of initial and final state contributions and implications on the physical meaning of Kohn-Sham energies.

    PubMed

    Pueyo Bellafont, Noèlia; Bagus, Paul S; Illas, Francesc

    2015-06-07

    A systematic study of the N(1s) core level binding energies (BE's) in a broad series of molecules is presented employing Hartree-Fock (HF) and the B3LYP, PBE0, and LC-BPBE density functional theory (DFT) based methods with a near HF basis set. The results show that all these methods give reasonably accurate BE's with B3LYP being slightly better than HF but with both PBE0 and LCBPBE being poorer than HF. A rigorous and general decomposition of core level binding energy values into initial and final state contributions to the BE's is proposed that can be used within either HF or DFT methods. The results show that Koopmans' theorem does not hold for the Kohn-Sham eigenvalues. Consequently, Kohn-Sham orbital energies of core orbitals do not provide estimates of the initial state contribution to core level BE's; hence, they cannot be used to decompose initial and final state contributions to BE's. However, when the initial state contribution to DFT BE's is properly defined, the decompositions of initial and final state contributions given by DFT, with several different functionals, are very similar to those obtained with HF. Furthermore, it is shown that the differences of Kohn-Sham orbital energies taken with respect to a common reference do follow the trend of the properly calculated initial state contributions. These conclusions are especially important for condensed phase systems where our results validate the use of band structure calculations to determine initial state contributions to BE shifts.

  13. Hematopoietic Progenitor Cell Rolling in Bone Marrow Microvessels: Parallel Contributions by Endothelial Selectins and Vascular Cell Adhesion Molecule 1

    PubMed Central

    Mazo, Irina B.; Gutierrez-Ramos, Jose-Carlos; Frenette, Paul S.; Hynes, Richard O.; Wagner, Denisa D.; von Andrian, Ulrich H.

    1998-01-01

    We have used intravital microscopy to study physiologically perfused microvessels in murine bone marrow (BM). BM sinusoids and venules, but not adjacent bone vessels, supported rolling interactions of hematopoietic progenitor cells. Rolling did not involve L-selectin, but was partially reduced in wild-type mice treated with antibodies to P- or E-selectin and in mice that were deficient in these two selectins. Selectin-independent rolling was mediated by α4 integrins, which interacted with endothelial vascular cell adhesion molecule (VCAM)-1. Parallel contribution of the endothelial selectins and VCAM-1 is not known to direct blood cell trafficking to other noninflamed tissues. This combination of constitutively expressed adhesion molecules may thus constitute a BM-specific recruitment pathway for progenitor cells analogous to the vascular addressins that direct selective lymphocyte homing to lymphoid organs. PMID:9687524

  14. Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion.

    PubMed

    Schaffer, Chris B; Friedman, Beth; Nishimura, Nozomi; Schroeder, Lee F; Tsai, Philbert S; Ebner, Ford F; Lyden, Patrick D; Kleinfeld, David

    2006-02-01

    A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology.

  15. Fucoidan Extracted from Hijiki Protects Brain Microvessel Endothelial Cells Against Diesel Exhaust Particle Exposure-Induced Disruption.

    PubMed

    Choi, Young-Sook; Eom, Sang-Yong; Kim, In-Soo; Ali, Syed F; Kleinman, Michael T; Kim, Yong-Dae; Kim, Heon

    2016-05-01

    This study was performed to evaluate the protective effects of fucoidan against the decreased function of primary cultured bovine brain microvessel endothelial cells (BBMECs) after exposure to diesel exhaust particles (DEPs). BBMECs were extracted from bovine brains and cultured until confluent. To evaluate the function of BBMECs, we performed a permeability test using cell-by-cell equipment and by Western blot analysis for zonular occludens-1 (ZO-1), which is a tight junction protein of BMECs, and evaluated oxidative stress in BBMECs using the DCFH-DA assay and the CUPRAC-BCS assay. The increased oxidative stress in BBMECs following DEP exposure was suppressed by fucoidan. In addition, permeability of BBMECs induced by DEP exposure was decreased by fucoidan treatment. Our results showed that fucoidan protects against BBMEC disruption induced by DEP exposure. This study provides evidence that fucoidan might protect the central nervous system (CNS) against DEP exposure.

  16. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.

    PubMed

    Adamson, R H; Clark, J F; Radeva, M; Kheirolomoom, A; Ferrara, K W; Curry, F E

    2014-04-01

    Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.

  17. Generation of Bioactive Oxylipins from Exogenously Added Arachidonic, Eicosapentaenoic and Docosahexaenoic Acid in Primary Human Brain Microvessel Endothelial Cells.

    PubMed

    Aukema, Harold M; Winter, Tanja; Ravandi, Amir; Dalvi, Siddhartha; Miller, Donald W; Hatch, Grant M

    2016-05-01

    The human blood-brain barrier (BBB) is the restrictive barrier between the brain parenchyma and the circulating blood and is formed in part by microvessel endothelial cells. The brain contains significant amounts of arachidonic acid (ARA), and docosahexaenoic acid (DHA), which potentially give rise to the generation of bioactive oxylipins. Oxylipins are oxygenated fatty acid metabolites that are involved in an assortment of biological functions regulating neurological health and disease. Since it is not known which oxylipins are generated by human brain microvessel endothelial cells (HBMECs), they were incubated for up to 30 min in the absence or presence of 0.1-mM ARA, eicosapentaenoic acid (EPA) or DHA bound to albumin (1:1 molar ratio), and the oxylipins generated were examined using high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Of 135 oxylipins screened in the media, 63 were present at >0.1 ng/mL at baseline, and 95 were present after incubation with fatty acid. Oxylipins were rapidly generated and reached maximum levels by 2-5 min. While ARA, EPA and DHA each stimulated the production of oxylipins derived from these fatty acids themselves, ARA also stimulated the production of oxylipins from endogenous 18- and 20-carbon fatty acids, including α-linolenic acid. Oxylipins generated by the lipoxygenase pathway predominated both in resting and stimulated states. Oxylipins formed via the cytochrome P450 pathway were formed primarily from DHA and EPA, but not ARA. These data indicate that HBMECs are capable of generating a plethora of bioactive lipids that have the potential to modulate BBB endothelial cell function.

  18. Fluctuations in the population density of Gram-negative bacteria in a chernozem in the course of a succession initiated by moistening and chitin and cellulose introduction

    NASA Astrophysics Data System (ADS)

    Polyanskaya, L. M.; Ivanov, K. E.; Zvyagintsev, D. G.

    2012-10-01

    The role has been studied of Gram-negative bacteria in the destruction of polymers widely spread in soils: chitin and cellulose. The introduction of chitin had no positive effect on the population density of Gram-negative bacteria, but it advanced the date of their appearance: the maximum population density of Gram-negative bacteria was recorded not on the 7th-15th day as in the control but much earlier, on the 3rd-7th day of the experiment. Consequently, the introduction of chitin as an additional source of nutrition promoted revealing of the Gram-negative bacteria already at the early stages of the succession. In the course of the succession, when the fungal mycelium begins to die off, the actinomycetic mycelium increases in length, i.e., Gram-negative bacteria are replaced at this stage with Gram-positive ones, the leading role among which belongs to actinomycetes. The growth rate of Gram-negative bacteria is higher than that of actinomycetes, so they start chitin utilization at the early stages of the succession, whereas actinomycetes dominate at the late stages. The population density of Gram-negative bacteria was lower under the anaerobic conditions as compared with that in the aerobic ones. The population density of Gram-negative bacteria in the lower layer of the A horizon and in the B horizon was slightly higher only in the case of the chitin introduction. When cellulose was introduced into the soil under aerobic conditions, the population density of Gram-negative bacteria in all the layers of the A horizon was maximal from the 14th to the 22nd day of the experiment. Cellulose was utilized in the soil mostly by fungi, and this was suggested by the increase of the length of the fungal mycelium. Simultaneously, an increase in the length of the actinomycetal mycelium was observed, as these organisms also perform cellulose hydrolysis in soils. The Gram-negative bacteria began to develop at the stage of the fungal mycelium destruction, which indirectly

  19. Dynamics of Gram-negative bacteria population density in a soil in the course of the succession initiated by chitin and cellulose

    NASA Astrophysics Data System (ADS)

    Konstantin, Ivanov; Lubov, Polyanskaya

    2014-05-01

    The functions of actinomycetes in polymer destruction in soil traditionally considered as the dominant, compare to another groups of bacteria. Gram-positive bacteria also have ecological functions in destruction of soil organic matter. The role of Gram-negative bacteria has been researched in the microbial succession in terms of polymers destruction, which are widely spreads in soils: chitin and cellulose. The method with nalidixic acid as an inhibitor of DNA division of Gram-negative bacteria was modified. By modified method microbial succession of Gram-negative bacteria in the different horizons of a chernozem under aerobic and anaerobic conditions was researched. Chitin and cellulose as the source of nutrients with moistening was used in experiments. The introduction of chitin had no positive effect on the population density of Gram-negative bacteria in a chernozem, but it advanced the date of their appearance in microbial succession: the maximum of Gram-negative bacteria population density was registered on the 3rd- 7th day of the experiment with adding chitin. Compare to the control, which one was without any nutrient adding this dynamics registered much earlier. Consequently, the introduction of chitin as an additional source of nutrition promoted revealing of the Gram-negative bacteria in soil already at the early stages of the succession. In the course of the succession, when the fungal mycelium begins to die off, the actinomycetic mycelium increases in length, i.e., Gram-negative bacteria are replaced at this stage with Gram-positive ones, the leading role among which belongs to actinomycetes. The growth rate of Gram-negative bacteria is higher than that of actinomycetes, so they start chitin utilization at the early stages of the succession, whereas actinomycetes dominate at the late stages. The population density of Gram-negative bacteria was lower under the anaerobic conditions as compared with that in the aerobic ones. The population density of Gram

  20. Initial experience with a multielectrode catheter equipped with the single-axis sensor technology for high-density electroanatomical mapping in a swine model.

    PubMed

    Beinart, Roy; Perna, Francesco; Danik, Stephan; Barrett, Conor D; Heist, E Kevin; Ruskin, Jeremy; Mansour, Moussa

    2010-12-01

    magnetic-based electroanatomical mapping systems are widely used during catheter ablation. Currently, the size of the sensor incorporated in the catheter to allow its localization is large, prohibiting the placement of more than one sensor on any single catheter. As a result, multielectrode catheters cannot be tracked by the magnetic-based mapping systems. Single-axis sensors (SAS) are new generation sensors that are significantly smaller in size. The small size of these new sensors allows the placement of more than one sensor on each catheter, allowing the tracking of multielectrode catheters. The objective of this study is to test the feasibility of creating high-density magnetic electroanatomical maps using a new generation multielectrode catheter equipped with the SAS technology. anatomical reconstruction of cardiac chambers and the aorta, together with activation mapping of the right atrium during both sinus rhythm and pacing-induced premature atrial contractions (PACs), were performed in 5 swine using both a conventional mapping catheter and the novel multielectrode catheter equipped with SAS. The multielectrode mapping provided a detailed definition of cardiac anatomy while requiring shorter acquisition times. In addition, mapping of PACs origin was significantly faster using the multielectrode catheter. the novel multielectrode catheter equipped with the SAS technology can be used in combination with magnetic electroanatomical mapping systems to generate high-density anatomical reconstructions and activation maps.

  1. Role of oxytocin in the initiation of term and preterm labor in rats: changes in oxytocin receptor density and plasma oxytocin concentration and the effect of an oxytocin antagonist, L-366,509.

    PubMed

    Kobayashi, M; Akahane, M; Minami, K; Moro, M; Ajisawa, Y; Inoue, Y; Kawarabayashi, T

    1999-03-01

    Our purpose was to compare the functional roles of oxytocin in term and preterm labor in rats by both biochemical and pharmacologic means. We determined the myometrial oxytocin receptor density and the maternal plasma concentrations of oxytocin and progesterone on gestational days 18, 20, and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm labor induced by the combined use of bilateral ovariectomy and estradiol injection. We also evaluated the effects of an oxytocin antagonist, L-366,509, on the initiation of both term and preterm labor. The number of tritiated oxytocin binding sites in myometrial membranes rapidly increased on gestational day 22 (morning) in rats with term labor. Plasma progesterone level decreased in an inverse fashion. A rapid increase in circulating oxytocin concentration was observed at the onset of delivery in rats in labor at term. Both the plasma oxytocin concentration and the receptor density had the same values in rats with preterm labor as in rats with term labor. L-366,509 delayed the initiation of labor in rats with term and preterm labor in a dose-dependent manner. It is confirmed biochemically and pharmacologically that oxytocin plays an important role in the initiation of both term and preterm labor in rats. The oxytocin antagonist examined was able to delay term and preterm labor, so it might prove useful in clinical practice for the treatment of preterm labor.

  2. The BErkeley Atmospheric CO2 Observation Network: design, calibration, and initial evaluation of a high-density CO2 surface network

    NASA Astrophysics Data System (ADS)

    Shusterman, A.; Teige, V.; Turner, A. J.; Newman, C.; Kim, J.; Cohen, R. C.

    2016-12-01

    Conventionally, ground-based carbon dioxide monitoring efforts rely on a small handful of costly instruments scattered thinly across large domains. While well characterizing total integrated emissions originating from a given metropolitan area, such approaches are ill suited to resolve the heterogeneous patterns of urban CO2 sources occurring within the domain, despite the fact that these sources are often regulated individually and independently of the regional total. To better observe said heterogeneities, we present the BErkeley Atmospheric CO2 Observation Network (BEACO2N), an ensemble of 28 moderate-cost CO2 and air quality sensing "nodes" distributed across and around the city of Oakland, California at 2 km intervals, constituting what is, to our knowledge, the highest density CO2 monitoring network to date. We evaluate the network on the basis of four performance parameters (cost, reliability, precision, and bias) and derive various post hoc mathematical treatments to compensate for the deleterious effects of meteorological variability, temporal drift, and uncharacterized atemporal biases on the sensor data. We find our approach to dependably provide observations of sufficient quality to faithfully represent intra-city phenomena while nonetheless remaining cost-competitive with sparser networks of more expensive instruments. Furthermore, preliminary analyses of the first three years of observations reveal small scale variability in CO2 concentrations that cannot be accurately captured by current mesoscale modeling techniques, reinforcing the importance of such high resolution top-down observational methodologies to our understanding of urban CO2 on the actual scales of emission and regulation.

  3. Estrogen Receptor Subtypes Mediate Distinct Microvascular Dilation and Reduction in [Ca2+]i in Mesenteric Microvessels of Female Rat

    PubMed Central

    Mazzuca, Marc Q.; Mata, Karina M.; Li, Wei; Rangan, Sridhar S.

    2015-01-01

    Estrogen interacts with estrogen receptors (ERs) to induce vasodilation, but the ER subtype and post-ER relaxation pathways are unclear. We tested if ER subtypes mediate distinct vasodilator and intracellular free Ca2+ concentration ([Ca2+]i) responses via specific relaxation pathways in the endothelium and vascular smooth muscle (VSM). Pressurized mesenteric microvessels from female Sprague-Dawley rats were loaded with fura-2, and the changes in diameter and [Ca2+]i in response to 17β-estradiol (E2) (all ERs), PPT (4,4′,4′′-[4-propyl-(1H)-pyrazole-1,3,5-triyl]-tris-phenol) (ERα), diarylpropionitrile (DPN) (ERβ), and G1 [(±)-1-[(3aR*,4S*,9bS*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro:3H-cyclopenta(c)quinolin-8-yl]-ethanon] (GPR30) were measured. In microvessels preconstricted with phenylephrine, ER agonists caused relaxation and decrease in [Ca2+]i that were with E2 = PPT > DPN > G1, suggesting that E2-induced vasodilation involves ERα > ERβ > GPR30. Acetylcholine caused vasodilation and decreased [Ca2+]i, which were abolished by endothelium removal or treatment with the nitric oxide synthase blocker Nω-nitro-l-arginine methyl ester (L-NAME) and the K+ channel blockers tetraethylammonium (nonspecific) or apamin (small conductance Ca2+-activated K+ channel) plus TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole) (intermediate conductance Ca2+-activated K+ channel), suggesting endothelium-derived hyperpolarizing factor–dependent activation of KCa channels. E2-, PPT-, DPN-, and G1-induced vasodilation and decreased [Ca2+]i were not blocked by L-NAME, TEA, apamin plus TRAM-34, iberiotoxin (large conductance Ca2+- and voltage-activated K+ channel), 4-aminopyridine (voltage-dependent K+ channel), glibenclamide (ATP-sensitive K+ channel), or endothelium removal, suggesting an endothelium- and K+ channel–independent mechanism. In endothelium-denuded vessels preconstricted with phenylephrine, high KCl, or the Ca2+ channel activator Bay K

  4. In Vivo Correlation of Glucose Metabolism, Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI

    PubMed Central

    Kubiessa, Klaus; Boehm, Andreas; Barthel, Henryk; Kluge, Regine; Kahn, Thomas; Sabri, Osama; Stumpp, Patrick

    2015-01-01

    Objective To demonstrate the feasibility of simultaneous acquisition of 18F-FDG-PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters. Methods 17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE. SUVmax, SUVmean, ADCmean, ADCmin and Ktrans, kep and ve were measured for each tumour and correlated using Spearman’s ρ. Results Significant correlations were observed between SUVmean and Ktrans (ρ = 0.43; p ≤ 0.05); SUVmean and kep (ρ = 0.44; p ≤ 0.05); Ktrans and kep (ρ = 0.53; p ≤ 0.05); and between kep and ve (ρ = -0.74; p ≤ 0.01). There was a trend towards statistical significance when correlating SUVmax and ADCmin (ρ = -0.35; p = 0.08); SUVmax and Ktrans (ρ = 0.37; p = 0.07); SUVmax and kep (ρ = 0.39; p = 0.06); and ADCmean and ve (ρ = 0.4; p = 0.06). Conclusion Simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density. PMID:26270054

  5. ELUCID—Exploring the Local Universe with the reConstructed Initial Density Field. II. Reconstruction Diagnostics, Applied to Numerical Halo Catalogs

    NASA Astrophysics Data System (ADS)

    Tweed, Dylan; Yang, Xiaohu; Wang, Huiyuan; Cui, Weiguang; Zhang, Youcai; Li, Shijie; Jing, Y. P.; Mo, H. J.

    2017-05-01

    The ELUCID project aims to build a series of realistic cosmological simulations that reproduce the spatial and mass distributions of the galaxies as observed in the Sloan Digital Sky Survey. This requires powerful reconstruction techniques to create constrained initial conditions (ICs). We test the reconstruction method by applying it to several N-body simulations. We use two medium-resolution simulations, which each produced three additional constrained N-body simulations. We compare the resulting friend-of-friend catalogs by using the particle indexes as tracers, and quantify the quality of the reconstruction by varying the main smoothing parameter. The cross-identification method we use proves to be efficient, and the results suggest that the most massive reconstructed halos are effectively traced from the same Lagrangian regions in the ICs. A preliminary time-dependence analysis indicates that high-mass-end halos converge only at a redshift close to the reconstruction redshift. This suggests that, for earlier snapshots, only collections of progenitors may be effectively cross-identified.

  6. 20-Hydroxyeicosatetraenoic Acid Contributes to the Inhibition of K+ Channel Activity and Vasoconstrictor Response to Angiotensin II in Rat Renal Microvessels

    PubMed Central

    Maier, Kristopher G.; Williams, Jan M.; Pabbidi, Malikarjuna R.; Didion, Sean P.; Falck, John R.; Zhuo, Jialong; Roman, Richard J.

    2013-01-01

    The present study examined whether 20-hydroxyeicosatetraenoic acid (HETE) contributes to the vasoconstrictor effect of angiotensin II (ANG II) in renal microvessels by preventing activation of the large conductance Ca2+-activated K+ channel (KCa) in vascular smooth muscle (VSM) cells. ANG II increased the production of 20-HETE in rat renal microvessels. This response was attenuated by the 20-HETE synthesis inhibitors, 17-ODYA and HET0016, a phospholipase A2 inhibitor AACOF3, and the AT1 receptor blocker, Losartan, but not by the AT2 receptor blocker, PD123319. ANG II (10-11 to 10-6 M) dose-dependently decreased the diameter of renal microvessels by 41 ± 5%. This effect was blocked by 17-ODYA. ANG II (10-7 M) did not alter KCa channel activity recorded from cell-attached patches on renal VSM cells under control conditions. However, it did reduce the NPo of the KCa channel by 93.4 ± 3.1% after the channels were activated by increasing intracellular calcium levels with ionomycin. The inhibitory effect of ANG II on KCa channel activity in the presence of ionomycin was attenuated by 17-ODYA, AACOF3, and the phospholipase C (PLC) inhibitor U-73122. ANG II induced a peak followed by a steady-state increase in intracellular calcium concentration in renal VSM cells. 17-ODYA (10-5 M) had no effect on the peak response, but it blocked the steady-state increase. These results indicate that ANG II stimulates the formation of 20-HETE in rat renal microvessels via the AT1 receptor activation and that 20-HETE contributes to the vasoconstrictor response to ANG II by blocking activation of KCa channel and facilitating calcium entry. PMID:24324797

  7. Targeted unlabeled multiple reaction monitoring analysis of cell markers for the study of sample heterogeneity in isolated rat brain cortical microvessels.

    PubMed

    Gomez-Zepeda, David; Chaves, Catarina; Taghi, Méryam; Sergent, Philippe; Liu, Wang-Qing; Chhuon, Cérina; Vidal, Michel; Picard, Martin; Thioulouse, Elizabeth; Broutin, Isabelle; Guerrera, Ida-Chiara; Scherrmann, Jean-Michel; Parmentier, Yannick; Decleves, Xavier; Menet, Marie-Claude

    2017-08-01

    Liquid chromatography coupled to tandem mass spectrometry-based targeted absolute protein quantification (in fmol of the analyte protein per μg of total protein) is employed for the molecular characterization of the blood-brain barrier using isolated brain microvessels. Nevertheless, the heterogeneity of the sample regarding the levels of different cells co-isolated within the microvessels and bovine serum albumin (BSA) contamination (from buffers) are not always evaluated. We developed an unlabeled targeted liquid chromatography coupled to tandem mass spectrometry method to survey the levels of endothelial cells (ECs), astrocytes, and pericytes, as well as BSA contaminant in rat cortical microvessels. Peptide peak identities were evaluated using a spectral library and chromatographic parameters. Sprague-Dawley rat microvessels obtained on three different days were analyzed with this method complemented by an absolute quantification multiple reaction monitoring method for transporter proteins P-gp, Bcrp, and Na(+) /K(+) ATPase pump using stable isotope labeled peptides as internal standard. Inter-day differences in the cell markers and BSA contamination were observed. Levels of cell markers correlated positively between each other. Then, the correlation between cell marker proteins and transporter proteins was evaluated to choose the best EC marker protein for protein quantification normalization. The membrane protein Pecam-1 showed a very high correlation with the EC-specific transporter P-gp (Pearson product-moment correlation coefficient (r) > 0.89) and moderate to high with Bcrp (r ≥ 0.77), that can be found also in pericytes and astrocytes. Therefore, Pecam-1 was selected as a marker for the normalization of the quantification of the proteins of endothelial cells. © 2017 International Society for Neurochemistry.

  8. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station

    PubMed Central

    Takano, Yoshio; Yoshimitsu, Kazuhiro; Omoto, Masayuki; Hashida, Ryuki; Tagawa, Yoshihiko; Inada, Tomohisa; Yamada, Shin; Ohshima, Hiroshi

    2015-01-01

    . Conclusions These results showed the orbital operation capability and utility, and the preventive effect of HTS for an astronaut’s musculoskeletal atrophy. The initial flight data together with the ground data obtained so far will be utilized in the future planning of human space exploration. PMID:26296204

  9. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

    PubMed

    Shiba, Naoto; Matsuse, Hiroo; Takano, Yoshio; Yoshimitsu, Kazuhiro; Omoto, Masayuki; Hashida, Ryuki; Tagawa, Yoshihiko; Inada, Tomohisa; Yamada, Shin; Ohshima, Hiroshi

    2015-01-01

    capability and utility, and the preventive effect of HTS for an astronaut's musculoskeletal atrophy. The initial flight data together with the ground data obtained so far will be utilized in the future planning of human space exploration.

  10. Skin stiffness determined from occlusion of a horizontally running microvessel in response to skin surface pressure: a finite element study of sacral pressure ulcers.

    PubMed

    Yamada, Hiroshi; Inoue, Yoshiaki; Shimokawa, Yuki; Sakata, Keisuke

    2017-01-01

    Pressure ulcers occur following sustained occlusion of microvessels at bony prominences under skin surface pressure (SSP). However, the mechanical conditions of the surrounding soft tissue leading to microvascular occlusion are not fully understood. This study determined the stiffness of homogenized skin with microvasculature at the sacrum that occludes microvessels at an SSP of 10 kPa (consistent with a standard mattress) and recovers from occlusion at 5 kPa (consistent with a pressure-redistribution mattress). We conducted two-dimensional finite element analyses under plane stress and plane strain conditions to determine the stiffness of the skin. The results for plane stress conditions show that the microvessel was occluded with a Young's modulus of 23 kPa in response to an SSP of 10 kPa at the center of the sacrum and that the circulation recovered following a reduction in the SSP to 5 kPa. The resulting Young's modulus is consistent with reported data. Our study indicates that the critical value of the SSP for microvascular occlusion is determined not only by the stiffness of homogenized skin with microvasculature but also by the intraluminal pressure, microvascular wall stiffness, and body support conditions.

  11. Simulated Red Blood Cell Motion in Microvessel Bifurcations: Effects of Cell-Cell Interactions on Cell Partitioning

    PubMed Central

    Barber, Jared O.; Restrepo, Juan M.; Secomb, Timothy W.

    2013-01-01

    Partitioning of red blood cell (RBC) fluxes between the branches of a diverging microvessel bifurcation is generally not proportional to the flow rates, as RBCs preferentially enter the higher-flow branch. A two-dimensional model for RBC motion and deformation is used to investigate the effects of cell-cell mechanical interactions on RBC partitioning in bifurcations. The RBC membrane and cytoplasm are represented by sets of viscoelastic elements immersed in a low Reynolds number flow. Several types of two-cell interactions that can affect partitioning are found. In the most frequent interactions, a `trade-off' occurs, in which a cell entering one branch causes a following cell to enter the other branch. Other types of interactions include `herding,' where the leading cell is caused to enter the same branch as the following cell, and `following,' where the trailing cell is caused to enter the same branch as the leading cell. The combined effect of these cell-cell interactions is a tendency towards more uniform partitioning, which results from the trade-off effect but is reduced by the herding and following effects. With increasing hematocrit, the frequency of interactions increases, and more uniform partitioning results. This prediction is consistent with experimental observations on how hematocrit affects RBC partitioning. PMID:23555330

  12. Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels.

    PubMed

    Arrigoni, Chiara; Bongio, Matilde; Talò, Giuseppe; Bersini, Simone; Enomoto, Junko; Fukuda, Junji; Moretti, Matteo

    2016-07-01

    A major challenge in the development of clinically relevant 3D tissue constructs is the formation of vascular networks for oxygenation, nutrient supply, and waste removal. To this end, this study implements a multimodal approach for the promotion of vessel-like structures formation in stiff fibrin hydrogels. Computational simulations have been performed to identify the easiest microchanneled configuration assuring normoxic conditions throughout thick cylindrical hydrogels (8 mm height, 6 mm ∅), showing that in our configuration a minimum of three microchannels (600 μm ∅), placed in a non-planar disposition, is required. Using small hydrogel bricks with oxygen distribution equal to the microchanneled configuration, this study demonstrates that among different culture conditions, co-culture of mesenchymal and endothelial cells supplemented with ANG-1 and VEGF leads to the most developed vascular network. Microchanneled hydrogels have been then cultured in the same conditions both statically and in a bioreactor for 7 d. Unexpectedly, the combination between shear forces and normoxic conditions is unable to promote microvascular networks formation in three-channeled hydrogels. Differently, application of either shear forces or normoxic conditions alone results in microvessels outgrowth. These results suggest that to induce angiogenesis in engineered constructs, complex interactions between several biochemical and biophysical parameters have to be modulated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Spectral imaging based in vivo model system for characterization of tumor microvessel response to vascular targeting agents

    NASA Astrophysics Data System (ADS)

    Wankhede, Mamta

    Functional vasculature is vital for tumor growth, proliferation, and metastasis. Many tumor-specific vascular targeting agents (VTAs) aim to destroy this essential tumor vasculature to induce indirect tumor cell death via oxygen and nutrition deprivation. The tumor angiogenesis-inhibiting anti-angiogenics (AIs) and the established tumor vessel targeting vascular disrupting agents (VDAs) are the two major players in the vascular targeting field. Combination of VTAs with conventional therapies or with each other, have been shown to have additive or supra-additive effects on tumor control and treatment. Pathophysiological changes post-VTA treatment in terms of structural and vessel function changes are important parameters to characterize the treatment efficacy. Despite the abundance of information regarding these parameters acquired using various techniques, there remains a need for a quantitative, real-time, and direct observation of these phenomenon in live animals. Through this research we aspired to develop a spectral imaging based mouse tumor system for real-time in vivo microvessel structure and functional measurements for VTA characterization. A model tumor system for window chamber studies was identified, and then combinatorial effects of VDA and AI were characterized in model tumor system. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  14. Lipopolysaccharide-induced apoptosis in transformed bovine brain endothelial cells and human dermal microvessel endothelial cells: the role of JNK.

    PubMed

    Karahashi, Hisae; Michelsen, Kathrin S; Arditi, Moshe

    2009-06-01

    Stimulation of transformed bovine brain endothelial cells (TBBEC) with LPS leads to apoptosis while human microvessel endothelial cells (HMEC) need the presence of cycloheximide (CHX) with LPS to induce apoptosis. To investigate the molecular mechanism of LPS-induced apoptosis in HMEC or TBBEC, we analyzed the involvement of MAPK and PI3K in TBBEC and HMEC. LPS-induced apoptosis in TBBEC was hallmarked by the activation of caspase 3, caspase 6, and caspase 8 after the stimulation of LPS, followed by poly(ADP-ribose) polymerase cleavage and lactate dehydrogenase release. We also observed DNA cleavage determined by TUNEL staining in TBBEC treated with LPS. Herbimycin A, a tyrosine kinase inhibitor, and SP600125, a JNK inhibitor, suppressed the activation of caspases and lactate dehydrogenase release. Moreover, a PI3K inhibitor (LY294002) suppressed activation of caspases and combined treatment with both SP600125 and LY294002 completely inhibited the activation of caspases. These results suggest that the JNK signaling pathway through the tyrosine kinase and PI3K pathways is involved in the induction of apoptosis in LPS-treated TBBEC. On the other hand, we observed sustained JNK activation in HMEC treated with LPS and CHX, and neither ERK1/2 nor AKT were activated. The addition of SP600125 suppressed phosphorylation of JNK and the activation of caspase 3 in HMEC treated with LPS and CHX. These results suggest that JNK plays an important role in the induction of apoptosis in endothelial cells.

  15. Quantitative analysis of microvessels in rat circumventricular organs and pituitary gland

    SciTech Connect

    Fenstermacher, J.; Gross, P.; Sposito, N.; Pettersen, S.; Blasberg, R.; Patlak, C.; Butler, A.

    1986-03-01

    The cerebral circumventricular organs (CVOs) and pituitary gland (PG) purportedly have dense, highly permeable capillary beds which allow for ready blood-tissue exchange of messenger molecules. Quantitation of various morphological and physiological features of the capillaries with CVOs and PG plus some brain structures which have tight or blood-brain barrier (BBB) capillaries was undertaken in rats using several radiolabeled markers, quantitative autoradiography, image analysis, and light and electron microscopic morphometry. Microvascular blood volumes in CVOs and PG were several times larger than in other brain areas (54-70 ..mu../g and 5-8 ..mu../g, respectively). Capillary density and surface area were generally much greater in CVOs and PG than in gray matter; however the highest values for these two parameters were found for the pituitary neural lobe (NL) and supraoptic nucleus (SON), which has BBB capillaries. The rate of capillary blood flow was highest in NL and was similar in the subfornical organ, median eminence, cerebral cortex and SON (1.5 ml/g/min). The transcapillary exchange of several markers was 200-500 times greater in CVOs and NL than in BBB capillaries.

  16. Cell-free layer development process in the entrance region of microvessels.

    PubMed

    Oulaid, Othmane; Zhang, Junfeng

    2015-08-01

    We simulated red blood cell flows through a finite length channel with a two-dimensional immersed boundary lattice Boltzmann model. The local instantaneous variation in wall-cell distance has been examined in details, and a nominal cell-free layer (CFL) thickness has been proposed. The CFL development process along the channel has been then analyzed, showing that the CFL thickness profile can be basically split into two regimes: the initial rapid increase due to cell migration and the later gradual growth due to cell reorganization. Effects of various hemorheological factors, such as rigidity, aggregation, hematocrit, and channel width, have also been investigated. The development length of the CFL to 90% of its final width ranges from 150 to 300 μm, and the development length is sensitive to changes in hemorheological conditions. The correlation between the CFL features and hemorheological parameters has also been explored. The simulation results have been compared to available experimental studies, and qualitative agreement has been noticed. In spite of the model limitations, this study reveals the complexity of CFL development process, and it could be useful for better understanding relevant processes and phenomena in the microcirculation.

  17. KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels

    PubMed Central

    Choi, Ji-Young; Yoon, Sang-Sun; Kim, Sang-Eun; Ahn Jo, Sangmee

    2017-01-01

    Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression. Inhibition of G9a and EZH2, histone methyltransferases responsible for methylation at H3K9 and H3K27, respectively as well as G9a overexpression demonstrated the involvement of G9a in TNF-α-induced ICAM1 expression and leukocyte adhesion and transmigration. A specific role for KDM4B, a histone demethylase targeting H3K9me2, in TNF-α-induced ICAM1 upregulation was validated with siRNA. Moreover, treating mice with a KDM4 inhibitor ML324 blocked TNF-α-mediated neutrophil adhesion. Similarly, TNF-α-induced VCAM1 expression was suppressed by G9a overexpression and KDM4B knockdown. Collectively, we demonstrated that modification of H3K9me2 by G9a and KDM4B regulates expression of vascular adhesion molecules, and that depletion of these proteins or KDM4B reduces inflammation-induced leukocyte extravasation. Thus, blocking ICAM1 or KDM4B could offer a novel therapeutic opportunity treating brain diseases. PMID:28327608

  18. Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration

    PubMed Central

    Hoehme, Stefan; Brulport, Marc; Bauer, Alexander; Bedawy, Essam; Schormann, Wiebke; Hermes, Matthias; Puppe, Verena; Gebhardt, Rolf; Zellmer, Sebastian; Schwarz, Michael; Bockamp, Ernesto; Timmel, Tobias; Hengstler, Jan G.; Drasdo, Dirk

    2010-01-01

    Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl4, a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named “hepatocyte-sinusoid alignment” (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues. PMID:20484673

  19. [Noninvasive estimation of human tissue respiration with wavelet-analysis of oxygen saturation and blood flow oscillations in microvessels].

    PubMed

    Krupatkin, A I

    2012-01-01

    Laser Doppler flowmetry, laser spectrophotometry of oxygen saturation and fluorescence determination of NAD-H/FAD ratio were carried out at 30 humans in the upper extremity skin zones with and without arteriole-venule anastomoses (AVA). For the first time it was shown that wavelet-analysis of oxygen saturation and microvascular blood flow oscillations was an effective approach to noninvasive estimation of skin oxygen extraction (OE) and oxygen consumption rate (OC). OE = (SaO2--SvO2)/SaO2, where SaO2 (%) and SvO2(%) are the oxygen saturation of arterial and venular blood, correspondingly. If the ratio between amplitudes of cardiac rhythm (Ac, p.u.) and respiratory rhythm (Ar, p.u.) Ac/Ar < or = 1, SvO2 = SO2. In the case of Ac/Ar >1, SvO2 = SO2/(Ac/Ar). OC = Mnutr x (SaO2-SvO2) in p.u. x %O2, where Mnutr--value of nutritive perfusion (p.u.). Mnutr = M/SI, where SI--shunting index of blood flow in microvessels. The values of perfusion, OE and OC were higher in the skin with AVA than in the skin without AVA. The values of perfusion and oxygen saturation were more variable in the skin with AVA. The greatest significance for tissue metabolism have the oxygen diffused from the smallest arterioles and capillaries. The contribution increased to tissue metabolism of total perfusion and of oxygen diffused from arterioles in the conditions of tissue ischemia.

  20. Role of endothelial Ca2+ stores in the regulation of hydraulic conductivity of Rana microvessels in vivo.

    PubMed

    Glass, C A; Bates, D O

    2003-04-01

    Vascular permeability is regulated by endothelial cytosolic Ca(2+) concentration ([Ca(2+)](i)). To determine whether vascular permeability is dependent on extracellular Ca(2+) influx or release of Ca(2+) from stores, hydraulic conductivity (L(p)) was measured in single perfused frog mesenteric microvessels in the presence and absence of Ca(2+) influx and store depletion. Prevention of Ca(2+) reuptake into stores by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) inhibition increased L(p) in the absence of extracellular Ca(2+) influx. L(p) was further increased when Ca(2+) influx was restored. Depletion of the Ca(2+) stores with ionomycin and SERCA inhibition increased L(p) in the presence and the absence of extracellular Ca(2+) influx. However, store depletion in itself did not significantly increase L(p) in the absence of active Ca(2+) release from stores into the cytoplasm. There was a significant positive correlation between baseline permeability and the magnitude of the responses to both Ca(2+) store release and Ca(2+) influx, indicating that the Ca(2+) regulating properties of the endothelial cells may regulate the baseline L(p). To investigate the role of Ca(2+) stores in regulation of L(p), the relationship between SERCA inhibition and store release was studied. The magnitude of the L(p) increase during SERCA inhibition significantly and inversely correlated with that during store release by Ca(2+) ionophore, implying that the degree of store depletion regulates the size of the increase on L(p). These data show that microvascular permeability in vivo can be increased by agents that release Ca(2+) from stores in the absence of Ca(2+) influx. They also show that capacitative Ca(2+) entry results in increased L(p) and that the size of the permeability increase can be regulated by the degree of Ca(2+) release.

  1. The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits.

    PubMed

    Shintani, Noriyuki; Ishiyama, Tadahiko; Kotoda, Masakazu; Asano, Nobumasa; Sessler, Daniel I; Matsukawa, Takashi

    2017-03-07

    Global brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia-reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion. Japanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10(-6) mol · L(-1) for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10(-6) mol · L(-1) starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10(-6) mol · L(-1) starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping. Mean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18-19%) and small (mean; 25-29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre

  2. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies

    PubMed Central

    Yu, Grace Z.; Aye, Christina Y.L.; Lewandowski, Adam J.; Davis, Esther F.; Khoo, Cheen P.; Newton, Laura; Yang, Cheng T.; Al Haj Zen, Ayman; Simpson, Lisa J.; O’Brien, Kathryn; Cook, David A.; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M.; Watt, Suzanne M.

    2016-01-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (−17.7±16.4% versus −9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  3. Anatomic distribution of nerves and microvascular density in the human anterior vaginal wall: prospective study.

    PubMed

    Li, Ting; Liao, Qinping; Zhang, Hong; Gao, Xuelian; Li, Xueying; Zhang, Miao

    2014-01-01

    The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot. Biopsies were drawn from a 12 o'clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5-immunoreactive nerves and smooth muscle actin-immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002). Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction.

  4. Complete blockade of the vasorelaxant effects of angiotensin-(1–7) and bradykinin in murine microvessels by antagonists of the receptor Mas

    PubMed Central

    Peiró, Concepción; Vallejo, Susana; Gembardt, Florian; Palacios, Erika; Novella, Susana; Azcutia, Verónica; Rodríguez-Mañas, Leocadio; Hermenegildo, Carlos; Sánchez-Ferrer, Carlos F; Walther, Thomas

    2013-01-01

    The heptapeptide angiotensin-(1–7) is a biologically active metabolite of angiotensin II, the predominant peptide of the renin–angiotensin system. Recently, we have shown that the receptor Mas is associated with angiotensin-(1–7)-induced signalling and mediates, at least in part, the vasodilatory properties of angiotensin-(1–7). However, it remained controversial whether an additional receptor could account for angiotensin-(1–7)-induced vasorelaxation. Here, we used two different angiotensin-(1–7) antagonists, A779 and d-Pro-angiotensin-(1–7), to address this question and also to study their influence on the vasodilatation induced by bradykinin. Isolated mesenteric microvessels from both wild-type and Mas-deficient C57Bl/6 mice were precontracted with noradrenaline, and vascular reactivity to angiotensin-(1–7) and bradykinin was subsequently studied using a small-vessel myograph. Furthermore, mechanisms for Mas effects were investigated in primary human umbilical vein endothelial cells. Both angiotensin-(1–7) and bradykinin triggered a concentration-dependent vasodilatation in wild-type microvessels, which was absent in the presence of a nitric oxide synthase inhibitor. In these vessels, the pre-incubation with the Mas antagonists A779 or d-Pro-angiotensin-(1–7) totally abolished the vasodilatory capacity of both angiotensin-(1–7) and bradykinin, which was nitric oxide mediated. Accordingly, Mas-deficient microvessels lacked the capacity to relax in response to either angiotensin-(1–7) or bradykinin. Pre-incubation of human umbilical vein endothelial cells with A779 prevented bradykinin-mediated NO generation and NO synthase phosphorylation at serine 1177. The angiotensin-(1–7) antagonists A779 and d-Pro-angiotensin-(1–7) equally block Mas, which completely controls the angiotensin-(1–7)-induced vasodilatation in mesenteric microvessels. Importantly, Mas also appears to be a critical player in NO-mediated vasodilatation induced by

  5. Complete blockade of the vasorelaxant effects of angiotensin-(1-7) and bradykinin in murine microvessels by antagonists of the receptor Mas.

    PubMed

    Peiró, Concepción; Vallejo, Susana; Gembardt, Florian; Palacios, Erika; Novella, Susana; Azcutia, Verónica; Rodríguez-Mañas, Leocadio; Hermenegildo, Carlos; Sánchez-Ferrer, Carlos F; Walther, Thomas

    2013-05-01

    The heptapeptide angiotensin-(1-7) is a biologically active metabolite of angiotensin II, the predominant peptide of the renin-angiotensin system. Recently, we have shown that the receptor Mas is associated with angiotensin-(1-7)-induced signalling and mediates, at least in part, the vasodilatory properties of angiotensin-(1-7). However, it remained controversial whether an additional receptor could account for angiotensin-(1-7)-induced vasorelaxation. Here, we used two different angiotensin-(1-7) antagonists, A779 and d-Pro-angiotensin-(1-7), to address this question and also to study their influence on the vasodilatation induced by bradykinin. Isolated mesenteric microvessels from both wild-type and Mas-deficient C57Bl/6 mice were precontracted with noradrenaline, and vascular reactivity to angiotensin-(1-7) and bradykinin was subsequently studied using a small-vessel myograph. Furthermore, mechanisms for Mas effects were investigated in primary human umbilical vein endothelial cells. Both angiotensin-(1-7) and bradykinin triggered a concentration-dependent vasodilatation in wild-type microvessels, which was absent in the presence of a nitric oxide synthase inhibitor. In these vessels, the pre-incubation with the Mas antagonists A779 or d-Pro-angiotensin-(1-7) totally abolished the vasodilatory capacity of both angiotensin-(1-7) and bradykinin, which was nitric oxide mediated. Accordingly, Mas-deficient microvessels lacked the capacity to relax in response to either angiotensin-(1-7) or bradykinin. Pre-incubation of human umbilical vein endothelial cells with A779 prevented bradykinin-mediated NO generation and NO synthase phosphorylation at serine 1177. The angiotensin-(1-7) antagonists A779 and d-Pro-angiotensin-(1-7) equally block Mas, which completely controls the angiotensin-(1-7)-induced vasodilatation in mesenteric microvessels. Importantly, Mas also appears to be a critical player in NO-mediated vasodilatation induced by renin-angiotensin system

  6. Neuropeptide degradation by large vessel and microvessel-derived endothelial cells in vitro: cell surface catabolism of thyrotropin releasing hormone (TRH).

    PubMed

    Rozental, J M; Kaminska, G; Turner, J; Schwartz, T; Cadahia, V; Brooks, B R

    1989-10-16

    Cell surface ectopeptidase activity of purified, cultured large vessel and microvessel-derived endothelial cells (EC) was studied. Degradation of thyrotropin releasing hormone (TRH), and production of cyclo-His-Pro was significantly increased (P less than 0.001) in large vessel EC compared with microcapillary EC. Since the rate of catabolism in the microvascular capillary bed is 5 times less than that in the large vessel wall, peptide concentrations are likely maintained longer in close proximity to their site of biosynthesis, where they are presumably most active.

  7. A three dimensional model of an ultrasound contrast agent gas bubble and its mechanical effects on microvessels

    PubMed Central

    Hosseinkhah, N.; Hynynen, K.

    2012-01-01

    Ultrasound contrast agents inside a microvessel, when driven by ultrasound, oscillate and induce mechanical stresses on the vessel wall. These mechanical stresses can produce beneficial therapeutic effects but also induce vessel rupture if the stresses are too high. Therefore, it is important to use sufficiently low pressure amplitudes to avoid rupturing the vessels while still inducing the desired therapeutic effects. In this work, we developed a comprehensive three dimensional model of a confined microbubble inside a vessel while considering the bubble shell properties, blood viscosity, vessel wall curvature and the mechanical properties of the vessel wall. Two bubble models with the assumption of a spherical symmetric bubble and a simple asymmetrical bubble were simulated. This work was validated with previous experimental results and enabled us to evaluate the microbubbles’ behaviour and the resulting mechanical stresses induced on the vessel walls. In this study the fluid shear and circumferential stresses were evaluated as indicators of the mechanical stresses. The effects of acoustical parameters, vessel viscoelasticity and rigidity, vessel/bubble size and off-center bubbles on bubble behaviour and stresses on the vessel were investigated. The fluid shear and circumferential stresses acting on the vessel varied with time and location. As the frequency changed, the microbubble oscillated with the highest amplitude at its resonance frequency which was different from the resonance frequency of an unbound bubble. The bubble resonance frequency increased as the rigidity of a flexible vessel increased. The fluid shear and circumferential stresses peaked at frequencies above the bubble’s resonance frequency. The more rigid the vessels were, the more damped the bubble oscillations. The synergistic effect of acoustic frequency and vessel elasticity had also been investigated, since the circumferential stress showed either an increasing trend or a decreasing one

  8. Unique cellular events occurring during the initial interaction of macrophages with matrix-retained or methylated aggregated low density lipoprotein (LDL). Prolonged cell-surface contact during which ldl-cholesteryl ester hydrolysis exceeds ldl protein degradation.

    PubMed

    Buton, X; Mamdouh, Z; Ghosh, R; Du, H; Kuriakose, G; Beatini, N; Grabowski, G A; Maxfield, F R; Tabas, I

    1999-11-05

    A critical event in atherogenesis is the interaction of arterial wall macrophages with subendothelial lipoproteins. Although most studies have investigated this interaction by incubating cultured macrophages with monomeric lipoproteins dissolved in media, arterial wall macrophages encounter lipoproteins that are mostly bound to subendothelial extracellular matrix, and these lipoproteins are often aggregated or fused. Herein, we utilize a specialized cell-culture system to study the initial interaction of macrophages with aggregated low density lipoprotein (LDL) bound to extracellular matrix. The aggregated LDL remains extracellular for a relatively prolonged period of time and becomes lodged in invaginations in the surface of the macrophages. As expected, the degradation of the protein moiety of the LDL was very slow. Remarkably, however, hydrolysis of the cholesteryl ester (CE) moiety of the LDL was 3-7-fold higher than that of the protein moiety, in stark contrast to the situation with receptor-mediated endocytosis of acetyl-LDL. Similar results were obtained using another experimental system in which the degradation of aggregated LDL protein was delayed by LDL methylation rather than by retention on matrix. Additional experiments indicated the following properties of this interaction: (a) LDL-CE hydrolysis is catalyzed by lysosomal acid lipase; (b) neither scavenger receptors nor the LDL receptor appear necessary for the excess LDL-CE hydrolysis; and (c) LDL-CE hydrolysis in this system is resistant to cellular potassium depletion, which further distinguishes this process from receptor-mediated endocytosis. In summary, experimental systems specifically designed to mimic the in vivo interaction of arterial wall macrophages with subendothelial lipoproteins have demonstrated an initial period of prolonged cell-surface contact in which CE hydrolysis exceeds protein degradation.

  9. Prediction of the invasion depth of superficial squamous cell carcinoma based on microvessel morphology: magnifying endoscopic classification of the Japan Esophageal Society.

    PubMed

    Oyama, Tsuneo; Inoue, Haruhiro; Arima, Miwako; Momma, Kumiko; Omori, Tai; Ishihara, Ryu; Hirasawa, Dai; Takeuchi, Manabu; Tomori, Akihisa; Goda, Kenichi

    2017-01-01

    Predicting invasion depth of superficial esophageal squamous cell carcinoma is crucial in determining the precise indication for endoscopic resection because the rate of lymph node metastasis increases in proportion to the invasion depth of the carcinoma. Previous studies have shown a close relationship between microvascular patterns observed by Narrow Band Imaging magnifying endoscopy and invasion depth of the superficial carcinoma. Thus, the Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating invasion depth of superficial esophageal squamous cell carcinomas. We conducted a prospective study to evaluate the diagnostic values of type B vessels in the pretreatment estimation of invasion depth of superficial esophageal squamous cell carcinomas utilizing JES classification, the criteria of which are based on the degree of irregularity in the microvascular morphology. Type A microvessels corresponded to noncancerous lesions and lack severe irregularity; type B, to cancerous lesions, and exhibit severe irregularity. Type B vessels were subclassified into B1, B2, and B3, diagnostic criteria for T1a-EP or T1a-LPM, T1a-MM or T1b-SM1, and T1b-SM2 tumors, respectively. We enrolled 211 patients with superficial esophageal squamous cell carcinoma. The overall accuracy of type B microvessels in estimating tumor invasion depth was 90.5 %. We propose that the newly developed JES magnifying endoscopic classification is useful in estimating the invasion depth of superficial esophageal squamous cell carcinoma.

  10. Density (DE)

    Treesearch

    John F. Caratti

    2006-01-01

    The FIREMON Density (DE) method is used to assess changes in plant species density and height for a macroplot. This method uses multiple quadrats and belt transects (transects having a width) to sample within plot variation and quantify statistically valid changes in plant species density and height over time. Herbaceous plant species are sampled with quadrats while...

  11. Exogenous arachidonic acid mediates permeability of human brain microvessel endothelial cells through prostaglandin E2 activation of EP3 and EP4 receptors.

    PubMed

    Dalvi, Siddhartha; Nguyen, Hieu H; On, Ngoc; Mitchell, Ryan W; Aukema, Harold M; Miller, Donald W; Hatch, Grant M

    2015-12-01

    The blood-brain barrier, formed by microvessel endothelial cells, is the restrictive barrier between the brain parenchyma and the circulating blood. Arachidonic acid (ARA; 5,8,11,14-cis-eicosatetraenoic acid) is a conditionally essential polyunsaturated fatty acid [20:4(n-6)] and is a major constituent of brain lipids. The current study examined the transport processes for ARA in confluent monolayers of human brain microvascular endothelial cells (HBMEC). Addition of radioactive ARA to the apical compartment of HBMEC cultured on Transwell(®) inserts resulted in rapid incorporation of radioactivity into the basolateral medium. Knock down of fatty acid transport proteins did not alter ARA passage into the basolateral medium as a result of the rapid generation of prostaglandin E2 (PGE2 ), an eicosanoid known to facilitate opening of the blood-brain barrier. Permeability following ARA or PGE2 exposure was confirmed by an increased movement of fluorescein-labeled dextran from apical to basolateral medium. ARA-mediated permeability was attenuated by specific cyclooxygenase-2 inhibitors. EP3 and EP4 receptor antagonists attenuated the ARA-mediated permeability of HBMEC. The results indicate that ARA increases permeability of HBMEC monolayers likely via increased production of PGE2 which acts upon EP3 and EP4 receptors to mediate permeability. These observations may explain the rapid influx of ARA into the brain previously observed upon plasma infusion with ARA. The blood-brain barrier, formed by microvessel endothelial cells, is a restrictive barrier between the brain parenchyma and the circulating blood. Radiolabeled arachidonic acid (ARA) movement across, and monolayer permeability in the presence of ARA, was examined in confluent monolayers of primary human brain microvessel endothelial cells (HBMECs) cultured on Transwell(®) plates. Incubation of HBMECs with ARA resulted in a rapid increase in HBMEC monolayer permeability. The mechanism was mediated, in part

  12. Density Visualization

    ERIC Educational Resources Information Center

    Keiter, Richard L.; Puzey, Whitney L.; Blitz, Erin A.

    2006-01-01

    Metal rods of high purity for many elements are now commercially available and may be used to construct a display of relative densities. We have constructed a display with nine metal rods (Mg, Al, Ti, V, Fe, Cu, Ag, Pb, and W) of equal mass whose densities vary from 1.74 to 19.3 g cm[superscript -3]. The relative densities of the metals may be…

  13. Density Visualization

    ERIC Educational Resources Information Center

    Keiter, Richard L.; Puzey, Whitney L.; Blitz, Erin A.

    2006-01-01

    Metal rods of high purity for many elements are now commercially available and may be used to construct a display of relative densities. We have constructed a display with nine metal rods (Mg, Al, Ti, V, Fe, Cu, Ag, Pb, and W) of equal mass whose densities vary from 1.74 to 19.3 g cm[superscript -3]. The relative densities of the metals may be…

  14. Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.

    PubMed

    Zimmerer, Rüdiger M; Matthiesen, Peter; Kreher, Fritjof; Kampmann, Andreas; Spalthoff, Simon; Jehn, Philipp; Bittermann, Gido; Gellrich, Nils-Claudius; Tavassol, Frank

    2016-03-01

    Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors.

  15. [Influence of polyethylene oxide Polyox WSR-301 on the pressure in mesenteric arterial microvessels in rats pre-adapted to anti-orthostatic states].

    PubMed

    Grigorian, S S; Sokolova, I A; Shakhnazarov, A A; Rudneva, R I; Timkina, M I

    1998-01-01

    High-molecular polymers apt to directly influence flow microstructure were tested as a fundamentally new method for correcting microhemodynamics in microgravity. Pressure in the mesenteric arterial microvessels was measured two weeks in rats adapted to the head-down suspension. Intravenous polyethylene oxide (Polyox WSR-301, end-concentration in the order of 2.10(-7) g/ml), reduced the microvascular pressure by 26%, whereas in the control pressure was reduced by only 15%. Systemic arterial pressure showed an equal drop in the groups (by 10 to 11%). These results suggest that the biomechanical agent weakens resistance to the blood flow in the body region where blood supply is impaired by microgravity.

  16. The permeation of dynorphin A 1-6 across the blood brain barrier and its effect on bovine brain microvessel endothelial cell monolayer permeability.

    PubMed

    Sloan, Courtney D Kuhnline; Audus, Kenneth L; Aldrich, Jane V; Lunte, Susan M

    2012-12-01

    Dynorphin A 1-17 (Dyn A 1-17) is an endogenous neuropeptide known to act at the kappa opioid receptor; it has been implicated in a number of neurological disorders, including neuropathic pain, stress, depression, and Alzheimer's and Parkinson's diseases. The investigation of Dyn A 1-17 metabolism at the blood-brain barrier (BBB) is important since the metabolites exhibit unique biological functions compared to the parent compound. In this work, Dyn A 1-6 is identified as a metabolite of Dyn A 1-17 in the presence of bovine brain microvessel endhothelial cells (BBMECs), using LC-MS/MS. The transport of Dyn A 1-6 at the BBB was examined using this in vitro cell culture model of the BBB. Furthermore, the permeation of the BBB by the low molecular weight permeability marker fluorescein was characterized in the presence and absences of Dyn A 1-6.

  17. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells.

    PubMed

    Mitchell, Ryan W; On, Ngoc H; Del Bigio, Marc R; Miller, Donald W; Hatch, Grant M

    2011-05-01

    The blood-brain barrier (BBB), formed by the brain capillary endothelial cells, provides a protective barrier between the systemic blood and the extracellular environment of the CNS. Passage of fatty acids from the blood to the brain may occur either by diffusion or by proteins that facilitate their transport. Currently several protein families have been implicated in fatty acid transport. The focus of the present study was to identify the fatty acid transport proteins (FATPs) expressed in the brain microvessel endothelial cells and characterize their involvement in fatty acid transport across an in vitro BBB model. The major fatty acid transport proteins expressed in human brain microvessel endothelial cells (HBMEC), mouse capillaries and human grey matter were FATP-1, -4 and fatty acid binding protein 5 and fatty acid translocase/CD36. The passage of various radiolabeled fatty acids across confluent HBMEC monolayers was examined over a 30-min period in the presence of fatty acid free albumin in a 1 : 1 molar ratio. The apical to basolateral permeability of radiolabeled fatty acids was dependent upon both saturation and chain length of the fatty acid. Knockdown of various fatty acid transport proteins using siRNA significantly decreased radiolabeled fatty acid transport across the HBMEC monolayer. Our findings indicate that FATP-1 and FATP-4 are the predominant fatty acid transport proteins expressed in the BBB based on human and mouse expression studies. While transport studies in HBMEC monolayers support their involvement in fatty acid permeability, fatty acid translocase/CD36 also appears to play a prominent role in transport of fatty acids across HBMEC.

  18. Cerebral microvessel perfusion and pathologic alteration of the brain during drowsiness and coma, caused by brain tumor (A laboratory study in rats)

    PubMed Central

    Hekmatpanah, Javad

    2007-01-01

    Background Deterioration of consciousness and coma, in cerebral compression, is traditionally thought to be caused by compression, shift, hemorrhage, or herniation of the brainstem. This study was done to evaluate the vascular perfusion and pathologic alteration in the entire brain during drowsiness and coma. Methods Brain tumors were developed in three newborn rat litters by inoculation of Kirsten Sarcoma Virus (a murine erythroblastosis virus) in the brains. Within several weeks brain tumors developed. When animals became drowsy or comatose, their brains were perfused with microbarium, India ink, or paraformaldehyde solution. In two animals, the brain vasculature was casted by plastic materials. Brains were fixed for magnification radiography, or were prepared for histological examination Results The brains of control animals showed an abundance of microvessels and penetrating capillaries, located perpendicular to the cortex and deep within the brain. The latter can not be detected even in the best routine cerebral angiography in man. Microvessels were obstructed, in a patchy and dispersed fashion, in drowsiness especially in ipsilateral hemisphere. Obstruction of microvessls was present not only in the brainstem but also was present in the rest of the brain and in cerebellum of comatose animals; larger vessels appeared markedly narrowed. The study also revealed evidence of diffuse infarcts, cellular ischemia, swelling, and periventricular damage throughout the brain. Conclusions During drowsiness and coma, caused by cerebral compression, cerebral capillaries progressively obstruct not only in the brain stem, but also throughout the brain; considerably more severe during coma than drowsiness. These likely causes diffuse neurological disabilities and behavioral changes often seen after recovery from coma caused by cerebral compression. PMID:17368521

  19. Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic[hCETP]-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats

    PubMed Central

    Bergerat, Agnes; Decano, Julius; Wu, Chang-Jiun; Choi, Hyungwon; Nesvizhskii, Alexey I; Moran, Ann Marie; Ruiz-Opazo, Nelson; Steffen, Martin; Herrera, Victoria LM

    2011-01-01

    Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor–induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non–stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke. PMID:21519634

  20. Adaptation to Survival in Germinal Center is the Initial Step in Onset of Indolent Stage of Multiple Myeloma

    PubMed Central

    Silva, Ariosto S.; Gatenby, Robert A.

    2011-01-01

    Aberrant mutations of centrocytes in germinal centers (GC) can generate two completely different diseases: B-cell lymphomas and monoclonal gammopathy of undetermined significance (MGUS). In this article we use computational models to examine the evolutionary dynamics by which initial adaptation to survival in the GC allows naïve MGUS cells to proliferate in the bone marrow and initiate the evolutionary process that will lead to aggressive multiple myeloma (MM). Our simulations show that MGUS cells may generate bone marrow tumors ranging from indolent to aggressive, depending on the original adaptation in the GC. All these tumors, however, are limited to approximately 15% of the marrow cellularity due to hypoxia-induced quiescence (this correlates with the cellularity that separates MGUS and MM, ~10%). Resistance to hypoxia-induced quiescence and cell death was one of the two major bone marrow adaptations that allowed continued tumor growth and establishment of paracrine cytokine loops, known to increase MM cell replication and de novo multidrug resistance. The second major adaptation was an increase in IL-6-independent growth rate, which correlates with the mutations observed in advanced stage patients. Even though there was an increase in the microvessel density in all simulations, the “angiogenic switch” was not due to a MM angiogenic phenotype, but rather the response of MM cells to the regional hypoxia caused by the increased tumor burden. These results indicate that treatments targeting the adaptation to survival and proliferation in hypoxia, in conjunction with currently available therapies, may have synergistic effects, by delaying tumor growth and reducing cytokine paracrine loops mediated by angiogenic factors. PMID:21958215

  1. Effect of Age of Self-Reported, Non-Surgical Menopause on Time to First Fracture and Bone Mineral Density in the Women’s Health Initiative Observational Study

    PubMed Central

    Lehman, Amy; Thomas, Fridtjof; Johnson, Karen C.; Jackson, Rebecca; Wactawski-Wende, Jean; Ko, Marcia; Chen, Zhao; Curb, J David; Howard, Barbara V.

    2015-01-01

    Objective Menopause is a risk factor for fracture, thus menopause age may affect bone mass and fracture rates. We compared Bone Mineral Density (BMD) and fracture rates among healthy postmenopausal women with varying ages of self-reported non-surgical menopause. Methods Hazard ratios for fracture and differences in BMD among 21,711 postmenopausal women from the Women’s Health Initiative Observational cohort without prior hysterectomy, oophorectomy, or hormone therapy, who reported age of menopause of <40, 40–49, or ≥50 years, were compared. Results Prior to multivariable adjustments, we found no differences in absolute fracture risk among menopausal age groups. After multivariable adjustments for known risk factors for fracture, women undergoing menopause <40 had a higher fracture risk at any site compared to women undergoing menopause ≥50 years (HR=1.21, 95% CI: 1.02, 1.44; p=0.03). In a subset with BMD measurements (n=1,351), whole body BMD was lower in women who reported menopause <40 compared to 40–49 years (estimated difference= −0.034 g/cm2; 95% CI: −0.07, −0.004; p=0.03) and compared to ≥50 years (estimated difference= −0.05 g/cm2; 95% CI; −0.08, −0.02; p<0.01). Left hip BMD was lower in women with menopause <40 compared to ≥50 years (estimated difference= −0.05 g/cm2; 95% CI: −0.08, −0.01; p=0.01), and total spine BMD was lower in women with menopause <40 compared to ≥50 and 40–49 years (estimated differences= −0.11 g/cm2; 95% CI; −0.16, −0.06; p<0.01 and −0.09 g/cm2; 95% CI; −0.15, −0.04; p<0.01, respectively). Conclusions In the absence of hormone therapy, earlier menopause age may be a risk factor contributing to decreased BMD and increased fracture risk in healthy postmenopausal women. Our data suggest that menopause age should be taken into consideration, along with other osteoporotic risk factors, when estimating fracture risk in postmenopausal women. PMID:25803670

  2. The association of red blood cell n-3 and n-6 fatty acids to dietary fatty acid intake, bone mineral density and hip fracture risk in The Women’s Health Initiative

    PubMed Central

    Orchard, Tonya S.; Ing, Steven W.; Lu, Bo; Belury, Martha A.; Johnson, Karen; Wactawski-Wende, Jean; Jackson, Rebecca D.

    2013-01-01

    Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) in red blood cells (RBC) are an objective indicator of PUFA status and may be related to hip fracture risk. The primary objective of this study was to examine RBC PUFAs as predictors of hip fracture risk in postmenopausal women. A nested case-control study (n=400 pairs) was completed within the Women’s Health Initiative (WHI) using 201 incident hip fracture cases from the Bone Mineral Density (BMD) cohort, along with 199 additional incident hip fracture cases randomly selected from the WHI Observational Study. Cases were 1:1 matched on age, race, and hormone use with non-hip fracture controls. Stored baseline RBCs were analyzed for fatty acids using gas chromatography. After removing degraded samples, 324 matched pairs were included in statistical analyses. Stratified Cox proportional hazard models were constructed according to case-control pair status; risk of fracture was estimated for tertiles of RBC PUFA. In adjusted hazard models, lower hip fracture risk was associated with higher RBC α-linolenic acid [Hazard ratio (HR) Tertile 3 (T3): 0.44; 95% CI: 0.23-0.85; p for linear trend 0.0154)], eicosapentaenoic acid (HR T3: 0.46; 95% CI: 0.24-0.87; p for linear trend 0.0181) and total n-3 PUFAs (HR T3: 0.55; 95% CI: 0.30-1.01; p for linear trend 0.0492). Conversely, hip fracture nearly doubled with the highest RBC n-6/n-3 ratio (HR T3: 1.96; 95% CI: 1.03-3.70; p for linear trend 0.0399). RBC PUFAs were not associated with BMD. RBC PUFAs were indicative of dietary intake of marine n-3 PUFAs (Spearman’s rho=0.45, p<0.0001), total n-6 PUFAs (rho=0.17, p<0.0001) and linoleic acid (rho= 0.09, p<0.05). These results suggest that higher RBC α-linolenic acid, as well as eicosapentaenoic acid and total n-3 PUFAs, may predict lower hip fracture risk. Contrastingly, a higher RBC n-6/n-3 ratio may predict higher hip fracture risk in postmenopausal women. PMID:23018646

  3. Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue.

    PubMed

    Laperle, Christopher M; Hamilton, Theron J; Wintermeyer, Philip; Walker, Evan J; Shi, Daxin; Anastasio, Mark A; Derdak, Zoltan; Wands, Jack R; Diebold, Gerald; Rose-Petruck, Christoph

    2008-12-07

    We report a new preparative method for providing contrast through reduction in electron density that is uniquely suited for propagation-based differential x-ray phase contrast imaging. The method, which results in an air or fluid filled vasculature, makes possible visualization of the smallest microvessels, roughly down to 15 microm, in an excised murine liver, while preserving the tissue for subsequent histological workup. We show the utility of spatial frequency filtering for increasing the visibility of minute features characteristic of phase contrast imaging, and the capability of tomographic reconstruction to reveal microvessel structure and three-dimensional visualization of the sample. The effect of water evaporation from livers during x-ray imaging on the visibility of blood vessels is delineated. The deformed vascular tree in a cancerous murine liver is imaged.

  4. Asteroid Densities

    NASA Astrophysics Data System (ADS)

    Britt, D. T.; Yeomans, D.; Housen, K.; Consolmagno, G.

    2005-01-01

    This data set contains a tabulation of asteroid masses, diameters, and bulk densities compiled by D. T. Britt and published in Table 1 of Britt, et al. (2002) [BRITTETAL2002] in the 'Asteroids III' volume.

  5. Ports Initiative

    EPA Pesticide Factsheets

    EPA's Ports Initiative works in collaboration with the port industry, communities, and government to improve environmental performance and increase economic prosperity. This effort helps people near ports breath cleaner air and live better lives.

  6. Event-by-event distribution of the ratio of magnetic field energy to initial fluid energy density in √{sN N}=200 GeV Au-Au collisions

    NASA Astrophysics Data System (ADS)

    Roy, Victor; Pu, Shi

    2015-12-01

    We estimate the event-by-event (e-by-e) distribution of the ratio (σ ) of the magnetic and electric field energy density to the fluid energy density in the transverse plane of Au-Au collisions at √{sN N}=200 GeV. A Monte Carlo (MC) Glauber model is used to calculate σ in the transverse plane for impact parameter b =0 , 12 fm at time τi˜0.5 fm. The fluid energy density is obtained by using Gaussian smoothing with two different smoothing parameter σg=0.25 , 0.5 fm. For b =0 fm collisions σ is found to be ≪1 in the central region of the fireball and σ ≳1 at the periphery. For b =12 fm collisions σ ≳1 is observed for some events. The e-by-e correlation between σ and the fluid energy density (ɛ ) is studied. We did not find strong correlation between σ and ɛ at the center of the fireball, whereas they are mostly anticorrelated at the periphery of the fireball.

  7. Ultrastructural analysis of contractile cell development in lung microvessels in hyperoxic pulmonary hypertension. Fibroblasts and intermediate cells selectively reorganize nonmuscular segments.

    PubMed Central

    Jones, R.

    1992-01-01

    The current study traces the development of contractile cells in the nonmuscular segments of rat lung microvessels in hyperoxic pulmonary hypertension. New intimal cells first develop into a well-defined layer beneath the endothelium and internal to an elastic lamina. Ultrastructurally, these cells are found to be 1) fibroblasts recruited to the vessel wall from the interstitium and 2) intermediate cells, a population of preexisting vascular cells (structurally between a smooth muscle cell and a pericyte). Early in hyperoxia (days 3 through 7), interstitial fibroblasts migrate and align around the smallest vessels in which an elastic lamina is either absent or fragmentary. These cells then are incorporated into the vessel wall by tropoelastin secretion and the formation of an elastic lamina along their abluminal margin. After day 7, the new mural fibroblasts acquire the features of contractile cells, namely a basal lamina, extensive microfilaments, and dense bodies. In other vessels, as early as day 3 of hyperoxia, intermediate cells within the vessel intima begin to acquire the additional filaments and dense bodies of contractile cells. As hyperoxia continues, each cell pathway gives rise to vessels with distinct intimal or medial layers of contractile cells. In this way, thick-walled 'newly muscularized' vessel segments form adjacent to the capillary bed. Images Figure 1 Figure 5 Figure 6 Figure 7 p1500-a Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:1466406

  8. Effects of deformability of RBCs on their dynamics and blood flow passing through a stenosed microvessel: an immersed boundary-lattice Boltzmann approach