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Sample records for lymphatic vascular development

  1. Lymphatic vascular morphogenesis in development, physiology, and disease

    NARCIS (Netherlands)

    Schulte-Merker, Stefan; Sabine, Amelie; Petrova, Tatiana V.

    2011-01-01

    The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many commo

  2. LYMPHATIC DEVELOPMENT

    OpenAIRE

    Butler, Matthew G; Isogai, Sumio; Weinstein, Brant M.

    2009-01-01

    The lymphatic system is essential for fluid homeostasis, immune responses, and fat absorption, and is involved in many pathological processes, including tumor metastasis and lymphedema. Despite its importance, progress in understanding the origins and early development of this system has been hampered by lack of defining molecular markers and difficulties in observing lymphatic cells in vivo and performing genetic and experimental manipulation of the lymphatic system. Recent identification of...

  3. Aberrant lymphatic endothelial progenitors in lymphatic malformation development.

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    June K Wu

    Full Text Available Lymphatic malformations (LMs are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4, circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2, and lymphatic endothelial proteins (podoplanin, VEGFR-3. Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133- cells isolated from LM fluids. CD133- LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133- LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.

  4. Lymphatic Vascular-Based Therapy for IBD

    Science.gov (United States)

    2012-07-01

    intestine which lead to a failure in normal intestinal lymphatic patterning and may be a model of human lymphedema distichiasis. These mice are... lymphedema distichiasis (humans) is not apparent, this is not seen in this model either. There is a reported apparent greater engorgement of lymphatic

  5. Altered Pulmonary Lymphatic Development in Infants with Chronic Lung Disease

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    Emily M. McNellis

    2014-01-01

    Full Text Available Pulmonary lymphatic development in chronic lung disease (CLD has not been investigated, and anatomy of lymphatics in human infant lungs is not well defined. Hypothesis. Pulmonary lymphatic hypoplasia is present in CLD. Method. Autopsy lung tissues of eighteen subjects gestational ages 22 to 40 weeks with and without history of respiratory morbidity were stained with monoclonal antipodoplanin and reviewed under light microscopy. Percentage of parenchyma podoplanin stained at the acinar level was determined using computerized image analysis; 9 CLD and 4 control subjects gestational ages 27 to 36 weeks were suitable for the analysis. Results. Distinct, lymphatic-specific staining with respect to other vascular structures was appreciated in all gestations. Infants with and without respiratory morbidity had comparable lymphatic distribution which extended to the alveolar ductal level. Podoplanin staining per parenchyma was increased and statistically significant in the CLD group versus controls at the alveolar ductal level (0.06% ± 0.02% versus 0.04% ± 0.01%, 95% CI −0.04% to −0.002%, P<0.03. Conclusion. Contrary to our hypothesis, the findings show that there is an increase in alveolar lymphatics in CLD. It is suggested that the findings, by expanding current knowledge of CLD pathology, may offer insight into the development of more effective therapies to tackle CLD.

  6. The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems.

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    Wu, Min; Frieboes, Hermann B; McDougall, Steven R; Chaplain, Mark A J; Cristini, Vittorio; Lowengrub, John

    2013-03-07

    The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform

  7. By Different Cellular Mechanisms, Lymphatic Vessels Sprout by Endothelial Cell Recruitment Whereas Blood Vessels Grow by Vascular Expansion

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    Parsons-Wingerter, Patricia; McKay, Terri L.; Leontiev, Dmitry; Condrich, Terence K.; DiCorleto, Paul E.

    2005-01-01

    The development of effective vascular therapies requires the understanding of all modes of vessel formation contributing to vasculogenesis, angiogenesis (here termed hemangiogenesis) and lymphangiogenesis. We show that lymphangiogenesis proceeds by blind-ended vessel sprouting via recruitment of isolated endothelial progenitor cells to the tips of growing vessels, whereas hemangiogenesis occurs by non-sprouting vessel expansion from the capillary network, during middevelopment in the quail chorioallantoic membrane (CAM). Blood vessels expanded out of capillaries that displayed transient expression of alpha smooth muscle actin (alphaSMA), accompanied by mural recruitment of migratory progenitor cells expressing SMA. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptors VEGFR-1 and VEGFR-2, alphaSMA (expressed on CAM blood vessels but not on lymphatics), homeobox transcription factor Prox-1 (specific to CAM lymphatic endothelium), and the quail hematopoetic/vascular marker, QH-1. Expression of VEGFR-1 was highly restricted to blood vessels (primarily capillaries). VEGFR-2 was expressed intensely in isolated hematopoietic cells, lymphatic vessels and moderately in blood vessels. Prox-1 was absent from endothelial progenitor cells prior to lymphatic recruitment. Although vascular endothelial growth factor-165 (VEGF(sub 165)) is a key regulator of numerous cellular processes in hemangiogenesis and vasculogenesis, the role of VEGF(sub 165) in lymphangiogenesis is less clear. Exogenous VEGF(sub 165) increased blood vessel density without changing endogenous modes of vascular/lymphatic vessel formation or marker expression patterns. However, VEGF(sub 165) did increase the frequency of blood vascular anastomoses and strongly induced the antimaturational dissociation of lymphatics from blood vessels, with frequent formation of homogeneous lymphatic networks.

  8. Lymphatic Vascular Regeneration : The Next Step in Tissue Engineering

    NARCIS (Netherlands)

    Huethorst, Eline; Krebber, Merle M; Fledderus, Joost O; Gremmels, Hendrik; Xu, Yan Juan; Pei, Jiayi; Verhaar, Marianne C; Cheng, Caroline

    2016-01-01

    The lymphatic system plays a crucial role in interstitial fluid drainage, lipid absorption, and immunological defense. Lymphatic dysfunction results in lymphedema, fluid accumulation, and swelling of soft tissues, as well as a potentially impaired immune response. Lymphedema significantly reduces qu

  9. Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer

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    L.R. Moreira

    2009-07-01

    Full Text Available Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis and D2-40 (marker for lymphatic endothelium. Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019 and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041 when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

  10. An inguinal mass with local vascular lesions induced by a lymphatic filaria.

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    Abdel-Hameed, Ahmed A; Dura, Wieslaw T; Alkhalife, Ibrahim S

    2004-08-01

    A 47-year-old Indian male presented with an inguinal mass clinically suspicious as a tumor. Histological examination of the excised mass demonstrated tissue reaction to degenerating intravascular adult filarial worms. The worms have been identified as a lymphatic filariae, most probably Wuchereria bancrofti. The case report underscores the need to maintain suspicion of genitourinary filarial lesions in non-endemic areas and describes atypical vascular lesions induced by lymphatic filariae.

  11. Anti-inflammatory pharmacotherapy with ketoprofen ameliorates experimental lymphatic vascular insufficiency in mice.

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    Kenta Nakamura

    Full Text Available BACKGROUND: Disruption of the lymphatic vasculature causes edema, inflammation, and end-tissue destruction. To assess the therapeutic efficacy of systemic anti-inflammatory therapy in this disease, we examined the impact of a nonsteroidal anti-inflammatory drug (NSAID, ketoprofen, and of a soluble TNF-alpha receptor (sTNF-R1 upon tumor necrosis factor (TNF-alpha activity in a mouse model of acquired lymphedema. METHODS AND FINDINGS: Lymphedema was induced by microsurgical ablation of major lymphatic conduits in the murine tail. Untreated control mice with lymphedema developed significant edema and extensive histopathological inflammation compared to sham surgical controls. Short-term ketoprofen treatment reduced tail edema and normalized the histopathology while paradoxically increasing TNF-alpha gene expression and cytokine levels. Conversely, sTNF-R1 treatment increased tail volume, exacerbated the histopathology, and decreased TNF-alpha gene expression. Expression of vascular endothelial growth factor-C (VEGF-C, which stimulates lymphangiogenesis, closely correlated with TNF-alpha expression. CONCLUSIONS: Ketoprofen therapy reduces experimental post-surgical lymphedema, yet direct TNF-alpha inhibition does not. Reducing inflammation while preserving TNF-alpha activity appears to optimize the repair response. It is possible that the observed favorable responses, at least in part, are mediated through enhanced VEGF-C signaling.

  12. Lymphatic Disorders

    Science.gov (United States)

    ... Overview of the Lymphatic System Swollen Lymph Nodes Lymphedema Like the venous system, the lymphatic system transports ... lymphatic system leads to an accumulation of fluid ( lymphedema ). Obstruction may result from scar tissue that develops ...

  13. Vascular, glial, and lymphatic immune gateways of the central nervous system.

    Science.gov (United States)

    Engelhardt, Britta; Carare, Roxana O; Bechmann, Ingo; Flügel, Alexander; Laman, Jon D; Weller, Roy O

    2016-09-01

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

  14. Differential Gene Expression of Primary Cultured Lymphatic and Blood Vascular Endothelial Cells

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    Gregory M. Nelson

    2007-12-01

    Full Text Available Blood vascular endothelial cells (BECs and the developmentally related lymphatic endothelial cells (LECs create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs, cytokines, cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, the neuronal growth factor regulator-1 and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1, the poliovirus receptor-related 3 molecule that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.

  15. Significance of periductal lymphatic and blood vascular densities in intraductal carcinoma of the breast.

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    El-Gohary, Yasser M; Metwally, Ghada; Saad, Reda S; Robinson, Morton J; Mesko, Thomas; Poppiti, Robert J

    2009-01-01

    We investigated the significance of periductal lymphatic and blood vascular densities in intraductal carcinomas (IDC) of the breast. Thirty five cases of pure IDC treated by partial or total mastectomy were reviewed. Seven cases with normal breast tissue and 48 cases of invasive breast carcinoma were included as controls. All cases were immunostained with D2-40 and CD31. Positively stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at 400x (=0.17 mm(2)) in the periductal areas. IDC without comedonecrosis showed a mean periductal D2-40 lymphatic microvessel density (LMD) of 5.8 +/- 5 (range 0-18), and a CD31 microvessel density (MD) of 14 +/- 8.9 (range 1-40). IDC with comedonecrosis showed periductal D2-40 LMD of 8.4 +/- 3.8 (range 4-18), and a CD31 MD of 24.3 +/- 7.6 (range 14-40). There was a significant difference between periductal D2-40 LMD and CD31 MD counts in IDC with and without comedonecrosis. There was a positive correlation of periductal D2-40 LMD and CD31 MD counts with high nuclear grade (r = 0.39 and 0.56) of IDC as well as with the presence of comedonecrosis (r = 0.49 and 0.59). Both D2-40 LMD and CD31 MD did not correlate significantly with tumor size, estrogen status, or progesterone status. As IDC with comedonecrosis and/or high nuclear grade has a worse prognosis than IDC without comedonecrosis and/or with low nuclear grade, it appears that lymphatic and blood vascular density evaluated by D2-40 and CD31, respectively, are independent prognostic indicators for patients with IDC of the breast and may be an indicator of early or unrecognized invasion or "regression."

  16. Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis

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    Fateye, B.; He, C.; Chen, B.

    2009-06-01

    Vascular targeting photodynamic therapy (vPDT) is currently in clinical trial for prostate cancer (PCa) treatment. In order to study the effect of vPDT on tumor metastasis, GFP-PC3 or PC-3 xenografts were treated with verteporfin (BPD) PDT. Vascular function was assessed by ultrasound imaging; lymph node and lung metastasis were assessed by fluorescence imaging. vPDT significantly reduced tumor blood flow within 30minutes to 2 hours of treatment. Sub-curative treatment resulted in re-perfusion within 2 weeks of treatment and increased lymph node metastasis. With curative doses, no metastasis was observed. In order to identify cellular or matrix factors and cytokines implicated, conditioned medium from BPD PDTtreated endothelial cells was incubated with PC3 cells in vitro. Tumor cell proliferation and migration was assessed. By immunoblotting, we evaluated the change in mediators of intracellular signaling or that may determine changes in tumor phenotype. Low sub-curative dose (200ng/ml BPD) of endothelial cells was associated with ~15% greater migration in PC3 cells when compared with control. This dose was also associated with sustained activation of Akt at Ser 473, an upstream effector in the Akt/ mTOR pathway that has been correlated with Gleason scores in PCa and with survival and metastasis in vitro and in vivo. In conclusion, the study implicates efficacy of PDT of endothelial cells as an important determinant of its consequences on adjacent tumor proliferation and metastasis.

  17. Transcription factor COUP-TFII is indispensable for venous and lymphatic development in zebrafish and Xenopus laevis

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    Aranguren, Xabier L., E-mail: xabier.lopezaranguren@med.kuleuven.be [Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Beerens, Manu, E-mail: manu.beerens@med.kuleuven.be [Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vandevelde, Wouter, E-mail: woutervandevelde@gmail.com [Vesalius Research Center, VIB, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vesalius Research Center, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Dewerchin, Mieke, E-mail: mieke.dewerchin@vib-kuleuven.be [Vesalius Research Center, VIB, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vesalius Research Center, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Carmeliet, Peter, E-mail: peter.carmeliet@vib-kuleuven.be [Vesalius Research Center, VIB, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Vesalius Research Center, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium); Luttun, Aernout, E-mail: aernout.luttun@med.kuleuven.be [Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs and Navorsing 1, Herestraat 49, B-3000 Leuven (Belgium)

    2011-06-24

    Highlights: {yields} COUP-TFII deficiency in zebrafish affects arterio-venous EC specification. {yields} COUP-TFII is indispensable for lymphatic development in zebrafish. {yields} COUP-TFII knockdown in Xenopus disrupts lymphatic EC differentiation and migration. {yields} COUP-TFII's role in EC fate decisions is evolutionary conserved. -- Abstract: Transcription factors play a central role in cell fate determination. Gene targeting in mice revealed that Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII, also known as Nuclear Receptor 2F2 or NR2F2) induces a venous phenotype in endothelial cells (ECs). More recently, NR2F2 was shown to be required for initiating the expression of Prox1, responsible for lymphatic commitment of venous ECs. Small animal models like zebrafish embryos and Xenopus laevis tadpoles have been very useful to elucidate mechanisms of (lymph) vascular development. Therefore, the role of NR2F2 in (lymph) vascular development was studied by eliminating its expression in these models. Like in mice, absence of NR2F2 in zebrafish resulted in distinct vascular defects including loss of venous marker expression, major trunk vessel fusion and vascular leakage. Both in zebrafish and Xenopus the development of the main lymphatic structures was severely hampered. NR2F2 knockdown significantly decreased prox1 expression in zebrafish ECs and the same manipulation affected lymphatic (L)EC commitment, migration and function in Xenopus tadpoles. Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved.

  18. Vascular development in Arabidopsis.

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    Ye, Zheng-Hua; Freshour, Glenn; Hahn, Michael G; Burk, David H; Zhong, Ruiqin

    2002-01-01

    Vascular tissues, xylem and phloem, form a continuous network throughout the plant body for transport of water, minerals, and food. Characterization of Arabidopsis mutants defective in various aspects of vascular formation has demonstrated that Arabidopsis is an ideal system for investigating the molecular mechanisms controlling vascular development. The processes affected in these mutants include initiation or division of procambium or vascular cambium, formation of continuous vascular cell files, differentiation of procambium or vascular cambium into vascular tissues, cell elongation, patterned secondary wall thickening, and biosynthesis of secondary walls. Identification of the genes affected by some of these mutations has revealed essential roles in vascular development for a cytokinin receptor and several factors mediating auxin transport or signaling. Mutational studies have also identified a number of Arabidopsis mutants defective in leaf venation pattern or vascular tissue organization in stems. Genetic evidence suggests that the vascular tissue organization is regulated by the same positional information that determines organ polarity.

  19. LYMPHATIC SYSTEM: A FORGOTTEN AREA?

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    G. P. Itkin

    2016-01-01

    Full Text Available Development of new methods of visualization of the lymphatic system and in the treatment of several pathologies associated with impaired lymph fl ow. The lymphatic system is an integral part of the circulation. One of the main functions of the lymphatic system is to transport residual interstitial fl uid from the tissue back to the venous system. Despite growing recognition of the role of the lymphatic system in many disease processes, the techniques for imaging and interventions on the lymphatic system have lagged behind the well-developed methods for imaging and interventions on the cardiovascular systems. This is primarily due to small size and variability in anatomy of the lymphatic vessels, and diffi culty of introducing contrast into lymphatic ducts. Due to lack of imaging and intervention options, the fl ow function of the lymphatic system was relatively ignored over the last few decades. Recently, there has been resurgence in the interest in the fl ow function of the interventions on the lymphatic system with the development of percutaneous minimally invasive techniques, such as thoracic duct embolization, to treat life threatening lymphatic leaks. Our group recently introduced two new methods of lymphatic imaging: intranodal lymphangiography and dynamic contrast MR lymphangiography. These methods have allowed further understanding of lymphatic anatomy, pathophysiology, lymphodynamics, as well as provided guidance for novel minimally invasive lymphatic interventions. Using new techniques, the group discovered the causes and then developed treatments for several fatal conditions effecting single ventricle patients including plastic bronchitis and protein loosing enteropathy. Treatment for other conditions has evolved as well including congenital lymphodysplasia, chylothorax, and chylous ascites. The study of the liver lymphatic system has been little explored despite its signifi cant relevance as exampled in ascites formation in

  20. Lymphatic vessels growing apart from blood vessels in transplanted corneas after the blockade of vascular endothelial growth factor C

    Institute of Scientific and Technical Information of China (English)

    Ye Hui; Yan Hao; Zhong Lei; Wang Tao; Deng Juan; Ling Shi-qi

    2016-01-01

    BACKGROUND:Corneal lymphangiogenesis is beneficial to the transport of corneal antigenic materials, and accelerates the process of antigen presentation, thereby playing an important role in corneal immunity. However, due to the paral el outgrowth of corneal blood and lymphatic vessels in transplanted corneas, it is often difficult to accurately evaluate the role of corneal lymphatic vessels in allograft rejection. OBJECTIVE:To explore the development of corneal lymphangiogenesis and angiogenesis in transplanted rat corneas after the blockade of vascular endothelial growth factor C (VEGF-C). METHODS:130 rats used to establish corneal al ogenic transplantation models were equally randomized into two groups:the anti-VEGF-C group and the control group. VEGF-C was blocked in the anti-VEGF-C group by intraperitoneal injection of neutralizing monoclonal anti-VEGF-C antibody every other day for 2 consecutive weeks. Meanwhile, rats in control groups received intraperitoneal injections of saline. Corneal angiogenesis and lymphangiogenesis were characterized using whole mount immunofluorescence, and the immune rejection of the grafts was evaluated by scoring the rejection index (RI). In addition, the expression of VEGF-C was examined by real-time PCR. The relationship of corneal lymphangiogenesis and angiogenesis to RI in transplanted corneas was also characterized. RESULTS AND CONCLUSION:VEGF-C expression was markedly downregulated after VEGF-C blockade. Corneal lymphangiogenesis developed in parallel with corneal angiogenesis in the control group. While there was a mild reduction in blood vessel area (BVA) and a significant decrease in lymphatic vessel area (LVA) in the anti-VEGF-C group (P0.05). the graft survival time in the anti-VEGF-C group was significantly increased compared with that in the control group (P<0.05). Our results show that the outgrowth of lymphatic vessels is separated from that of blood vessels in transplanted corneas by blocking VEGF-C. The blockade

  1. Enzyme-histochemical study on postnatal development of rat stomach lymphatic vessels.

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    Ji, R C; Kato, S

    1997-07-01

    Postnatal development of rat gastric lymphatics was studied by an enzyme-histochemical method to elucidate the morphological changes of lymphatics and their relationship to maturation and function, especially in the glandular portion. The significant features of 5'-Nase-positive lymphatics in distribution and structure were examined in different stages (within 24 hr, 4-21 days, and 2 months). Lymphatics in the greater curvature and anterior wall grew much slower than those in the lesser curvature and posterior wall of the stomach in newborn and infant rats. Lymphatic islands isolated from the primary lymphatic networks in the submucosa and subserosa underwent a morphological change during this early period. This is considered one of the basic steps in lymphatic development. Occurrence of lymphatic networks in the deep lamina propria indicates that development in the gastric wall is well characterized from Day 10. With further growth and modification of lymphatics, the networks in the different layers formed an extensive communication network and many lymphatic valves were found in the submucosa and subserosa. Pinocytotic vesicles, open junctions, and intraendothelial channels were frequently detected in the mucosal and submucosal lymphatic networks of the corpus-antrum and antrum-duodenum divisional zones in the adult rats. These findings suggest that developing lymphatics in the rat stomach may represent rapidly growing tissue not only with high 5'-Nase activity but also with high adaptability for future physiological demands.

  2. Development of polygonal-surface version of ICRP reference phantoms: Lymphatic node modeling

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    Thang, Ngyen Tat; Yeom, Yeon Soo; Han, Min Cheol; Kim, Chan Hyeong [Hanyang University, Seoul (Korea, Republic of)

    2014-04-15

    Among radiosensitive organs/tissues considered in ICRP Publication 103, lymphatic nodes are many small size tissues and widely distributed in the ICRP reference phantoms. It is difficult to directly convert lymphatic nodes of ICRP reference voxel phantoms to polygonal surfaces. Furthermore, in the ICRP reference phantoms lymphatic nodes were manually drawn only in six lymphatic node regions and the reference number of lymphatic nodes reported in ICRP Publication 89 was not considered. To address aforementioned limitations, the present study developed a new lymphatic node modeling method for the polygonal-surface version of ICRP reference phantoms. By using the developed method, lymphatic nodes were modelled in the preliminary version of ICRP male polygonal-surface phantom. Then, lymphatic node dose values were calculated and compared with those of the ICRP reference male voxel phantom to validate the developed modeling method. The present study developed the new lymphatic node modeling method and successfully modeled lymphatic nodes in the preliminary version of the ICRP male polygonal-surface phantom. From the results, it was demonstrated that the developed modeling method can be used to model lymphatic nodes in polygonal-surface version of ICRP reference phantoms.

  3. Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas

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    Yanagawa, Takashi, E-mail: tyanagaw@med.gunma-u.ac.jp [Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan); Shinozaki, Tetsuya [Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan); Watanabe, Hideomi [Department of Physical Therapy, Gunma University School of Health Science, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan); Saito, Kenichi [Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan); Raz, Avraham [Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University, 110 E. Warren Ave., Detroit, MI (United States); Takagishi, Kenji [Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22, Showa, Maebashi, Gunma, 371-8511 (Japan)

    2012-04-15

    Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both in primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10{sup -8} and VEGF-D at 10{sup -7}and 10{sup -8} g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.

  4. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

    Science.gov (United States)

    Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

    2015-06-29

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

  5. Characteristics and prognostic value of lymphatic and blood vascular microinvasion in lung cancer.

    Science.gov (United States)

    Arame, Alex; Mordant, Pierre; Cazes, Aurélie; Foucault, Christophe; Dujon, Antoine; Le Pimpec Barthes, Françoise; Riquet, Marc

    2012-11-01

    The prognostic value of vascular microinvasion (VMI) in non-small cell lung cancer (NSCLC) has been a matter of discussion in recent decades. The last T N M classification does not take VMI into account, but many points remain questionable. A retrospective study was performed of patients undergoing operations for NSCLC during a 20-year period. Lymphatic VMI (LVMI) was classified as group (G) 1, blood VMI (BVMI) as G2, LVMI and BVMI as G3, and no VMI as G4. The demographic, pathologic, T N M characteristics, and long-term survival of each group were analyzed. A total of 3,868 patients (G1, 334; G2, 642; G3, 172; G4, 2,720), mean age 61.9 ± 10.1 years, underwent different types of resection, with complete lymphadenectomy in 88.5%. Adenocarcinomas were more frequent in G1 and G3, and squamous cell carcinomas in G2. In G2, more N1 tumors needed more extensive resections. G1 was equally distributed regardless of tumor size, but G2 prevalence increased with augmenting size. Nodules in the same lobe were significantly more frequent in LVMI than in BVMI. After exclusion of patients with R1 and R2 resections, multivariate analysis confirmed that LVMI and BVMI were independent prognostic factors as well as age, sex, type of resection, T extension, and N involvement. VMI is generally associated with a poorer prognosis. LVMI is less frequent than BVMI but has lower survival rates. The benefit of adjuvant therapy in VMI patients needs to be evaluated. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. The development of coronary vascular system

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    Олена Олександрівна Яковець

    2015-05-01

    Full Text Available Aim. Set the terms of occurrence and morphological markers of coronary vessels in the embryonic period of human ontogenesis.Material and methods. To realize the aim of our work the embryos of human heart from 5 th to 8 th week of prenatal development period were investigated in the amount of 60. The obtained specimens were evaluated by immunohistochemical study. For this purpose, the original monoclonal antibodies have been used, such as transcription factor Prox-1, cell proliferation marker Ki-67, an endothelial marker CD-34 and smooth-muscle actin (α-SMA. To identify the reaction the solution of chromogen 3-diaminobenzidine tetrachloride was applied, which is manifested in a rich brown color in the sensitive cells of the cardiac wall.Conclusions: The morphological specialization of vascular links of coronary system in the embryonic period has a natural sequence - acquisition of venous properties at first and parallel differentiation of arterial structures. After arteriovenous determination the next phase begins – lymphatic specialization of venous endothelial cells with the formation of lymphatic links of coronary vascular system

  7. Prospective transcriptomic pathway analysis of human lymphatic vascular insufficiency: identification and validation of a circulating biomarker panel.

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    Shin Lin

    Full Text Available BACKGROUND: In our previous transcriptional profiling of a murine model, we have identified a remarkably small number of specific pathways with altered expression in lymphedema. In this investigation, we utilized microarray-based transcriptomics of human skin for an unbiased a priori prospective candidate identification, with subsequent validation of these candidates through direct serum assay. The resulting multi-analyte biomarker panel sensitively should sensitively discriminate human lymphedema subjects from normal individuals. METHODS AND FINDINGS: We enrolled 63 lymphedema subjects and 27 normals in our attempt to discover protein analytes that can distinguish diseased individuals from controls. To minimize technical and biologically irrelevant variation, we first identified potential candidates by performing transcriptional microarray analysis on paired diseased and normal skin specimens sampled from the same individuals. We focused our attention on genes with corresponding protein products that are secreted and took these candidates forward to a protein multiplex assay applied to diseased and normal subjects. We developed a logistic regression-based model on an eventual group of six proteins and validated our system on a separate cohort of study subjects. The area under the receiver operating characteristic curve was calculated to be 0.87 (95% CI : 0.75 to 0.97. CONCLUSIONS: We have developed an accurate bioassay utilizing proteins representing four central pathogenetic modalities of the disease: lymphangiogenesis, inflammation, fibrosis, and lipid metabolism, suggesting that these proteins are directly related to the pathogenesis of the tissue pathology in lymphatic vascular insufficiency. Further studies are warranted to determine whether this newly-identified biomarker panel will possess utility as an instrument for in vitro diagnosis of early and latent disease; the ultimate applicability to risk stratification, quantitation of

  8. Vascular, glial, and lymphatic immune gateways of the central nervous system

    NARCIS (Netherlands)

    Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

    2016-01-01

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. R

  9. Vascular, glial, and lymphatic immune gateways of the central nervous system

    NARCIS (Netherlands)

    Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

  10. Lymphatic imaging in unsedated infants and children

    Science.gov (United States)

    Rasmussen, John C.; Balaguru, Duraisamy; Douglas, William I.; Breinholt, John P.; Greives, Matthew R.; Aldrich, Melissa B.; Sevick-Muraca, Eva M.

    2017-02-01

    Primary lymphedema and lymphatic malformations in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the underlying anatomy and function of the lymphatic system. Diagnostics for the lymphatic vasculature are limited, consisting of lymphoscintigraphy or invasive lymphangiography, both of which require sedation that can restrict use in infants and children. As a result, therapeutic protocols for pediatric patients with lymphatic disorders remain sparse and with little evidence to support them. Because near-infrared fluorescence (NIRF) imaging enables image acquisition on the order of tenths of seconds with trace administration of fluorescent dye, sedation is not necessary. The lack of harmful radiation and radioactive contrast agents further facilitates imaging. Herein we summarize our experiences in imaging infants and children who are suspected to have disorders of the lymphatic vascular system using indocyanine green (ICG) and who have developed chylothorax following surgery for congenital heart defects. The results show both anatomical as well as functional lymphatic deficits in children with congenital disease. In the future, NIRF lymphatic imaging could provide new opportunities to tailor effective therapies and monitor responses. The opportunity to use expand NIRF imaging for pediatric diagnostics beyond the lymphatic vasculature is also afforded by the rapid acquisition following trace administration of NIRF contrast agent.

  11. Integrin-α5β1 is not required for mural cell functions during development of blood vessels but is required for lymphatic-blood vessel separation and lymphovenous valve formation.

    Science.gov (United States)

    Turner, Christopher J; Badu-Nkansah, Kwabena; Crowley, Denise; van der Flier, Arjan; Hynes, Richard O

    2014-08-15

    Integrin α5β1 is essential for vascular development but it remains unclear precisely where and how it functions. Here, we report that deletion of the gene encoding the integrin-α5 subunit (Itga5) using the Pdgfrb-Cre transgenic mouse line, leads to oedema, haemorrhage and increased levels of embryonic lethality. Unexpectedly, these defects were not caused by loss of α5 from Pdgfrb-Cre expressing mural cells (pericytes and vascular smooth muscle cells), which wrap around the endothelium and stabilise blood vessels, nor by defects in the heart or great vessels, but were due to abnormal development of the lymphatic vasculature. Reminiscent of the pathologies seen in the human lymphatic malformation, fetal cystic hygroma, α5 mutants display defects both in the separation of their blood and lymphatic vasculature and in the formation of the lymphovenous valves. As a consequence, α5-deficient mice develop dilated, blood-filled lymphatic vessels and lymphatic capillaries that are ectopically covered with smooth muscle cells. Analysis of the expression of Pdgfrb during lymphatic development suggests that these defects probably arise from loss of α5β1 integrin in subsets of specialised Prox1(+)Pdgfrb(+) venous endothelial cells that are essential for the separation of the jugular lymph sac from the cardinal vein and formation of the lymphovenous valve leaflets.

  12. cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels

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    Lukas Stanczuk

    2015-03-01

    Full Text Available Pathological lymphatic diseases mostly affect vessels in specific tissues, yet little is known about organ-specific regulation of the lymphatic vasculature. Here, we show that the vascular endothelial growth factor receptor 3 (VEGFR-3/p110α PI3-kinase signaling pathway is selectively required for the formation of mesenteric lymphatic vasculature. Using genetic lineage tracing, we demonstrate that part of the mesenteric lymphatic vasculature develops from cKit lineage cells of hemogenic endothelial origin through a process we define as lymphvasculogenesis. This is contrary to the current dogma that all mammalian lymphatic vessels form by sprouting from veins. Our results reveal vascular-bed-specific differences in the origin and mechanisms of vessel formation, which may critically underlie organ-specific manifestation of lymphatic dysfunction in disease. The progenitor cells identified in this study may be exploited to restore lymphatic function following cancer surgery, lymphedema, or tissue trauma.

  13. Plant vascular development

    NARCIS (Netherlands)

    Rybel, De Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate

  14. Aberrant mural cell recruitment to lymphatic vessels and impaired lymphatic drainage in a murine model of pulmonary fibrosis.

    Science.gov (United States)

    Meinecke, Anna-Katharina; Nagy, Nadine; Lago, Gabriela D'Amico; Kirmse, Santina; Klose, Ralph; Schrödter, Katrin; Zimmermann, Annika; Helfrich, Iris; Rundqvist, Helene; Theegarten, Dirk; Anhenn, Olaf; Orian-Rousseau, Véronique; Johnson, Randall S; Alitalo, Kari; Fischer, Jens W; Fandrey, Joachim; Stockmann, Christian

    2012-06-14

    Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)-β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.

  15. Laminins and retinal vascular development.

    Science.gov (United States)

    Edwards, Malia M; Lefebvre, Olivier

    2013-01-01

    The mechanisms controlling vascular development, both normal and pathological, are not yet fully understood. Many diseases, including cancer and diabetic retinopathy, involve abnormal blood vessel formation. Therefore, increasing knowledge of these mechanisms may help develop novel therapeutic targets. The identification of novel proteins or cells involved in this process would be particularly useful. The retina is an ideal model for studying vascular development because it is easy to access, particularly in rodents where this process occurs post-natally. Recent studies have suggested potential roles for laminin chains in vascular development of the retina. This review will provide an overview of these studies, demonstrating the importance of further research into the involvement of laminins in retinal blood vessel formation.

  16. Transplantation of artificial human lymphatic vascular tissues fabricated using a cell-accumulation technique and their engraftment in mouse tissue with vascular remodeling.

    Science.gov (United States)

    Asano, Yoshiya; Shimoda, Hiroshi; Matsusaki, Michiya; Akashi, Mitsuru

    2017-09-06

    Transplantation of engineered tissues with microvascular structure is advancing towards therapeutic application to improve the flow of blood and/or lymphatic fluids. In lymphatic disorders, transplantation of tissue-engineered lymphatic grafts can be an ideal treatment for draining excessive lymphatic fluid. In this study, we examined the transplantation of three-dimensional artificial human lymphatic network tissue (AHLT) fabricated by the cell accumulation technique into the subcutaneous tissue and fascia of mice. At 2 weeks after transplantation, the AHLT showed engraftment of artificial lymphatic vessels immunopositive for human CD31 and human podoplanin. Notably, we also observed the generation of blood vessel-like structure comprising endothelial cells immunopositive for human CD34 and mural-like cells immunopositive for human CD90 and αSMA, which were considered as myofibroblasts. In the fabrication of AHLT in vitro, the sporadic emergence of human CD34-positive / Prox-1-negative sites was observed, followed by the formation of blood vessel-like structure in the graft within 7 days after transplantation. The fine structure of engrafted AHLT observed by transmission electron microscopy showed that the engrafted artificial lymphatic vessels possess the specific structures of native lymphatic capillaries such as loose inter-endothelial connections and anchoring filaments. In contrast, blood vessel-like structure showed tight inter-endothelial connections, thick basement membranes, and layers of mural-like cells, which resemble small blood vessels. These results suggested the remodeling of artificial lymphatic network to form blood vessel-like structure associated with mural-like cells along with AHLT fabrication and engraftment. This article is protected by copyright. All rights reserved.

  17. Role of Hyperplasia of Gingival Lymphatics in Periodontal Inflammation.

    Science.gov (United States)

    Papadakou, P; Bletsa, A; Yassin, M A; Karlsen, T V; Wiig, H; Berggreen, E

    2017-04-01

    Lymphatic vessels are important for maintenance of tissue fluid homeostasis and afferent antigen transport. In chronic inflammation, lymphangiogenesis takes place and is characterized by lymphatic endothelial cell proliferation and lymphatic hyperplasia. Vascular endothelial growth factor C (VEGFC) is the main known lymphangiogenic growth factor, and its expression is increased in periodontitis, a common chronic infectious disease that results in tissue destruction and alveolar bone loss. The role of lymphangiogenesis during development of periodontitis is unknown. Here, we test if transgenic overexpression of epithelial VEGFC in a murine model is followed by hyperplasia of lymphatic vessels in oral mucosa and if the lymphatic drainage capacity is altered. We also test if lymphatic hyperplasia protects against periodontal disease development. Transgenic keratin 14 (K14)-VEGFC mice had significant hyperplasia of lymphatics in oral mucosa, including gingiva, without changes in blood vessel vasculature. The basal lymph flow was normal but slightly lower than in wild-type mice when oral mucosa was challenged with lipopolysaccharide from Porphyromonas gingivalis. Under normal conditions, K14-VEGFC mice exhibited an increased number of neutrophils in gingiva, demonstrated enhanced phagocyte recruitment in the cervical lymph nodes, and had more alveolar bone when compared with their wild-type littermates. After induction of periodontitis, no strain differences were observed in the periodontal tissues with respect to granulocyte recruitment, bone resorption, angiogenesis, cytokines, and bone-related protein expressions or in draining lymph node immune cell proportions and vascularization. We conclude that overexpression of VEGFC results in hyperplastic lymphatics, which do not enhance lymphatic drainage capacity but facilitate phagocyte transport to draining lymph nodes. Hyperplasia of lymphatics does not protect against development of ligature-induced periodontitis.

  18. Vascular instruction of pancreas development.

    Science.gov (United States)

    Cleaver, Ondine; Dor, Yuval

    2012-08-01

    Blood vessels course through organs, providing them with essential nutrient and gaseous exchange. However, the vasculature has also been shown to provide non-nutritional signals that play key roles in the control of organ growth, morphogenesis and homeostasis. Here, we examine a decade of work on the contribution of vascular paracrine signals to developing tissues, with a focus on pancreatic β-cells. During the early stages of embryonic development, blood vessels are required for pancreas specification. Later, the vasculature constrains pancreas branching, differentiation and growth. During adult life, capillaries provide a vascular niche for the maintenance of β-cell function and survival. We explore the possibility that the vasculature constitutes a dynamic and regionalized signaling system that carries out multiple and changing functions as it coordinately grows with the pancreatic epithelial tree.

  19. Bioengineering dermo-epidermal skin grafts with blood and lymphatic capillaries.

    Science.gov (United States)

    Marino, Daniela; Luginbühl, Joachim; Scola, Simonetta; Meuli, Martin; Reichmann, Ernst

    2014-01-29

    The first bioengineered, autologous, dermo-epidermal skin grafts are presently undergoing clinical trials; hence, it is reasonable to envisage the next clinical step at the forefront of plastic and burn surgery, which is the generation of autologous skin grafts that contain vascular plexuses, preformed in vitro. As the importance of the blood, and particularly the lymphatic vascular system, is increasingly recognized, it is attractive to engineer both human blood and lymphatic vessels in one tissue or organ graft. We show here that functional lymphatic capillaries can be generated using three-dimensional hydrogels. Like normal lymphatics, these capillaries branch, form lumen, and take up fluid in vitro and in vivo after transplantation onto immunocompromised rodents. Formation of lymphatic capillaries could be modulated by both lymphangiogenic and anti-lymphangiogenic stimuli, demonstrating the potential usefulness of this system for in vitro testing. Blood and lymphatic endothelial cells never intermixed during vessel development, nor did blood and lymphatic capillaries anastomose under the described circumstances. After transplantation of the engineered grafts, the human lymphatic capillaries anastomosed to the nude rat's lymphatic plexus and supported fluid drainage. Successful preclinical results suggest that these skin grafts could be applied on patients suffering from severe skin defects.

  20. Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development.

    Science.gov (United States)

    van Lessen, Max; Shibata-Germanos, Shannon; van Impel, Andreas; Hawkins, Thomas A; Rihel, Jason; Schulte-Merker, Stefan

    2017-05-12

    The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain.

  1. Development and validation of a custom made indocyanine green fluorescence lymphatic vessel imager

    Science.gov (United States)

    Pallotta, Olivia J.; van Zanten, Malou; McEwen, Mark; Burrow, Lynne; Beesley, Jack; Piller, Neil

    2015-06-01

    Lymphoedema is a chronic progressive condition often producing significant morbidity. An in-depth understanding of an individual's lymphatic architecture is valuable both in the understanding of underlying pathology and for targeting and tailoring treatment. Severe lower limb injuries resulting in extensive loss of soft tissue require transposition of a flap consisting of muscle and/or soft tissue to close the defect. These patients are at risk of lymphoedema and little is known about lymphatic regeneration within the flap. Indocyanine green (ICG), a water-soluble dye, has proven useful for the imaging of lymphatic vessels. When injected into superficial tissues it binds to plasma proteins in lymph. By exposing the dye to specific wavelengths of light, ICG fluoresces with near-infrared light. Skin is relatively transparent to ICG fluorescence, enabling the visualization and characterization of superficial lymphatic vessels. An ICG fluorescence lymphatic vessel imager was manufactured to excite ICG and visualize real-time fluorescence as it travels through the lymphatic vessels. Animal studies showed successful ICG excitation and detection using this imager. Clinically, the imager has assisted researchers to visualize otherwise hidden superficial lymphatic pathways in patients postflap surgery. Preliminary results suggest superficial lymphatic vessels do not redevelop in muscle flaps.

  2. Lymphatic function is required prenatally for lung inflation at birth

    Science.gov (United States)

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  3. microRNAs in the Lymphatic Endothelium: Master Regulators of Lineage Plasticity and Inflammation

    Science.gov (United States)

    Yee, Daniel; Coles, Mark C.; Lagos, Dimitris

    2017-01-01

    microRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expression at the posttranscriptional level. They have crucial roles in organismal development, homeostasis, and cellular responses to pathological stress. The lymphatic system is a large vascular network that actively regulates the immune response through antigen trafficking, cytokine secretion, and inducing peripheral tolerance. Here, we review the role of miRNAs in the lymphatic endothelium with a particular focus on their role in lymphatic endothelial cell (LEC) plasticity, inflammation, and regulatory function. We highlight the lineage plasticity of LECs during inflammation and the importance of understanding the regulatory role of miRNAs in these processes. We propose that targeting miRNA expression in lymphatic endothelium can be a novel strategy in treating human pathologies associated with lymphatic dysfunction.

  4. Rapamycin Inhibits Lymphatic Endothelial Cell Tube Formation by Downregulating Vascular Endothelial Growth Factor Receptor 3 Protein Expression

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    Yan Luo

    2012-03-01

    Full Text Available Mammalian target of rapamycin (mTOR controls lymphangiogenesis. However, the underlying mechanism is not clear. Here we show that rapamycin suppressed insulin-like growth factor 1 (IGF-1- or fetal bovine serum (FBS-stimulated lymphatic endothelial cell (LEC tube formation, an in vitro model of lymphangiogenesis. Expression of a rapamycin-resistant and kinase-active mTOR (S2035T, mTOR-T, but not a rapamycin-resistant and kinase-dead mTOR (S2035T/D2357E, mTOR-TE, conferred resistance to rapamycin inhibition of LEC tube formation, suggesting that rapamycin inhibition of LEC tube formation is mTOR kinase activity dependent. Also, rapamycin inhibited proliferation and motility in the LECs. Furthermore, we found that rapamycin inhibited protein expression of VEGF receptor 3 (VEGFR-3 by inhibiting protein synthesis and promoting protein degradation of VEGFR-3 in the cells. Down-regulation of VEGFR-3 mimicked the effect of rapamycin, inhibiting IGF-1- or FBS-stimulated tube formation, whereas over-expression of VEGFR-3 conferred high resistance to rapamycin inhibition of LEC tube formation. The results indicate that rapamycin inhibits LEC tube formation at least in part by downregulating VEGFR-3 protein expression.

  5. The Role of Lymphatic Endothelial Cells in Liver Injury and Tumor Development

    Science.gov (United States)

    Lukacs-Kornek, Veronika

    2016-01-01

    Lymphatics and lymphatic endothelial cells (LECs) possess multiple immunological functions besides affecting immune cell migration, such as inhibiting T cell proliferation and antigen presentation by dendritic cells. Moreover, they control the trans-endothelial transport of multiple molecules and antigens. Emerging evidence suggest their active involvements in immunregulation, tumor, and metastases formation. In the liver, increased lymphangiogenesis, specifically at the portal area has been associated with multiple liver diseases in particular primary biliary cirrhosis, idiopathic portal hypertension, and liver malignancies. Nevertheless, the exact role and contribution of LECs to liver diseases are poorly understood. The review summarizes the current understanding of LECs in liver diseases. PMID:27965673

  6. The role of lymphatic endothelial cells in liver injury and tumor development

    Directory of Open Access Journals (Sweden)

    Veronika Lukacs-Kornek

    2016-11-01

    Full Text Available Lymphatics and lymphatic endothelial cells (LECs possess multiple immunological functions besides affecting immune cell migration such as inhibiting T cell proliferation and antigen presentation by dendritic cells. Moreover, they control the trans-endothelial transport of multiple molecules and antigens. Emerging evidence suggests their active involvements in immunoregulation, tumor and metastases formation. In the liver, increased lymphangiogenesis, specifically at the portal area has been associated with multiple liver diseases in particular primary biliary cirrhosis, idiopathic portal hypertension, and liver malignancies. Nevertheless, the exact role and contribution of LECs to liver diseases are poorly understood. The review summarizes the current understanding of LECs in liver diseases.

  7. Placental growth factor and vascular endothelial growth factor receptor-2 in human lung development.

    Science.gov (United States)

    Janér, Joakim; Andersson, Sture; Haglund, Caj; Karikoski, Riitta; Lassus, Patrik

    2008-08-01

    We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants. Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of 10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week. In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 +/- 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity. The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia

  8. Effect of water resource development and management on lymphatic filariasis, and estimates of populations at risk.

    Science.gov (United States)

    Erlanger, Tobias E; Keiser, Jennifer; Caldas De Castro, Marcia; Bos, Robert; Singer, Burton H; Tanner, Marcel; Utzinger, Jürg

    2005-09-01

    Lymphatic filariasis (LF) is a debilitating disease overwhelmingly caused by Wuchereria bancrofti, which is transmitted by various mosquito species. Here, we present a systematic literature review with the following objectives: (i) to establish global and regional estimates of populations at risk of LF with particular consideration of water resource development projects, and (ii) to assess the effects of water resource development and management on the frequency and transmission dynamics of the disease. We estimate that globally, 2 billion people are at risk of LF. Among them, there are 394.5 million urban dwellers without access to improved sanitation and 213 million rural dwellers living in close proximity to irrigation. Environmental changes due to water resource development and management consistently led to a shift in vector species composition and generally to a strong proliferation of vector populations. For example, in World Health Organization (WHO) subregions 1 and 2, mosquito densities of the Anopheles gambiae complex and Anopheles funestus were up to 25-fold higher in irrigated areas when compared with irrigation-free sites. Although the infection prevalence of LF often increased after the implementation of a water project, there was no clear association with clinical symptoms. Concluding, there is a need to assess and quantify changes of LF transmission parameters and clinical manifestations over the entire course of water resource developments. Where resources allow, integrated vector management should complement mass drug administration, and broad-based monitoring and surveillance of the disease should become an integral part of large-scale waste management and sanitation programs, whose basic rationale lies in a systemic approach to city, district, and regional level health services and disease prevention.

  9. Stem cell function during plant vascular development.

    Science.gov (United States)

    Miyashima, Shunsuke; Sebastian, Jose; Lee, Ji-Young; Helariutta, Yka

    2013-01-23

    The plant vascular system, composed of xylem and phloem, evolved to connect plant organs and transport various molecules between them. During the post-embryonic growth, these conductive tissues constitutively form from cells that are derived from a lateral meristem, commonly called procambium and cambium. Procambium/cambium contains pluripotent stem cells and provides a microenvironment that maintains the stem cell population. Because vascular plants continue to form new tissues and organs throughout their life cycle, the formation and maintenance of stem cells are crucial for plant growth and development. In this decade, there has been considerable progress in understanding the molecular control of the organization and maintenance of stem cells in vascular plants. Noticeable advance has been made in elucidating the role of transcription factors and major plant hormones in stem cell maintenance and vascular tissue differentiation. These studies suggest the shared regulatory mechanisms among various types of plant stem cell pools. In this review, we focus on two aspects of stem cell function in the vascular cambium, cell proliferation and cell differentiation.

  10. Novel function for blood platelets and podoplanin in developmental separation of blood and lymphatic circulation.

    Science.gov (United States)

    Uhrin, Pavel; Zaujec, Jan; Breuss, Johannes M; Olcaydu, Damla; Chrenek, Peter; Stockinger, Hannes; Fuertbauer, Elke; Moser, Markus; Haiko, Paula; Fässler, Reinhard; Alitalo, Kari; Binder, Bernd R; Kerjaschki, Dontscho

    2010-05-13

    During embryonic development, lymph sacs form from the cardinal vein, and sprout centrifugally to form mature lymphatic networks. Separation of the lymphatic from the blood circulation by a hitherto unknown mechanism is essential for the homeostatic function of the lymphatic system. O-glycans on the lymphatic endothelium have recently been suggested to be required for establishment and maintenance of distinct blood and lymphatic systems, primarily by mediating proper function of podoplanin. Here, we show that this separation process critically involves platelet activation by podoplanin. We found that platelet aggregates build up in wild-type embryos at the separation zone of podoplanin(+) lymph sacs and cardinal veins, but not in podoplanin(-/-) embryos. Thus, podoplanin(-/-) mice develop a "nonseparation" phenotype, characterized by a blood-filled lymphatic network after approximately embryonic day 13.5, which, however, partially resolves in postnatal mice. The same embryonic phenotype is also induced by treatment of pregnant mice with acetyl salicylic acid, podoplanin-blocking antibodies, or by inactivation of the kindlin-3 gene required for platelet aggregation. Therefore, interaction of endothelial podoplanin of the developing lymph sac with circulating platelets from the cardinal vein is critical for separating the lymphatic from the blood vascular system.

  11. ETS transcription factors in embryonic vascular development.

    Science.gov (United States)

    Craig, Michael P; Sumanas, Saulius

    2016-07-01

    At least thirteen ETS-domain transcription factors are expressed during embryonic hematopoietic or vascular development and potentially function in the formation and maintenance of the embryonic vasculature or blood lineages. This review summarizes our current understanding of the specific roles played by ETS factors in vasculogenesis and angiogenesis and the implications of functional redundancies between them.

  12. Design and development of multilayer vascular graft

    Science.gov (United States)

    Madhavan, Krishna

    2011-07-01

    strength, showed that the multilayer graft possessed properties mimicking those of native vessels. Achieving these FDA-required functional properties is essential because they play critical roles in graft performances in vivo such as thrombus formation, occlusion, healing, and bleeding. In addition, cell studies and animal studies have been performed on the multilayer graft. Our results show that the multilayer graft support mimetic vascular culture of cells and the acellular graft serves as an artery equivalent in vivo to sustain the physiological conditions and promote appropriate cellular activity. In conclusion, the newly-developed hybrid multilayer graft provides a proper balance of biomechanical and biochemical properties and demonstrates the potential for the use of vascular tissue engineering and regeneration.

  13. Lymphatic Education & Research Network

    Science.gov (United States)

    Lymphatic Education & Research Network Donate Now Become a Supporting Member X Living with LYMPHEDEMA AND Lymphatic Disease FAQs About ... 261 Madison Avenue, New York, NY 10016 | Lymphatic Education & Research Network is a 501(c)(3) under ...

  14. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk.

    Science.gov (United States)

    Bussmann, Jeroen; Bos, Frank L; Urasaki, Akihiro; Kawakami, Koichi; Duckers, Henricus J; Schulte-Merker, Stefan

    2010-08-01

    The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk consisting of three types of lymphatic vessels that develop in close connection with the blood vasculature. We have generated transgenic lines that allow us to distinguish between arterial, venous and lymphatic endothelial cells (LECs) within a single zebrafish embryo. We found that LECs migrate exclusively along arteries in a manner that suggests that arterial endothelial cells serve as the LEC migratory substrate. In the absence of intersegmental arteries, LEC migration in the trunk is blocked. Our data therefore demonstrate a crucial role for arteries in LEC guidance.

  15. Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability.

    Directory of Open Access Journals (Sweden)

    Miwa Sato

    Full Text Available We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs and lymphatic endothelial cells (LECs were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate.

  16. Lymphatic regulation in nonmammalian vertebrates.

    Science.gov (United States)

    Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

    2013-08-01

    All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

  17. Vascular development in the vertebrate pancreas.

    Science.gov (United States)

    Azizoglu, D Berfin; Chong, Diana C; Villasenor, Alethia; Magenheim, Judith; Barry, David M; Lee, Simon; Marty-Santos, Leilani; Fu, Stephen; Dor, Yuval; Cleaver, Ondine

    2016-12-01

    The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow.

    Science.gov (United States)

    Datar, Sanjeev A; Johnson, Eric G; Oishi, Peter E; Johengen, Michael; Tang, Eric; Aramburo, Angela; Barton, Jubilee; Kuo, Hsuan-Chang; Bennett, Stephen; Xoinis, Konstantine; Reel, Bhupinder; Kalkan, Gokhan; Sajti, Eniko; Osorio, Oscar; Raff, Gary W; Matthay, Michael A; Fineman, Jeffrey R

    2012-03-15

    Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

  19. Stewart-Treves syndrome angiosarcoma expresses phenotypes of both blood and lymphatic capillaries

    Institute of Scientific and Technical Information of China (English)

    Marek Stanczyk; Magdalena Gewartowska; Marcin Swierkowski; Bartlomiej Grala; Marek Maruszynski

    2013-01-01

    Background The development of angiosarcoma in oedematous tissue is referred to as Stewart-Treves syndrome (STS).This rare and fatal complication is associated with chronic post mastectomy lymphoedema and radiotherapy for breast cancer.Angiosarcoma spread is facilitated by the formation of blood vessels (angiogenesis) and lymph vessels (lymphangiogenesis).In the future antiangiogenic therapy may improve the poor outcome of current treatments.There was evidence that blocking the angiogenenesis would inhibit progression of angiosarcoma.It seems reasonable to hypothesize that blocking the lymphangiogenesis may yield similar results.Although angiosarcomas commonly derive from blood vessels,in case of STS angiosarcomas chronic lymphoedema may suggest its lymphatic origin.The goal of this study was to visualize interstitial space and lymphatics in the central and peripheral regions of STS angiosarcoma.Methods On tissue samples obtained from STS angiosarcoma we have performed:first colour stereoscopic lymphography to visualise the morphology of lymphatic vessels and extracellular spaces,second immunohistochemical staining specific for lymphatic vessels endothelium (LYVE-1) and blood endothelial cells (CD31,factor Ⅷ) and prolymphangiogenic vascular endothelial growth factor (VEGF-C) for precise identification of lymphatic endothelia.STS angiosarcoma morphology was assessed by comparison of pictures obtained on lymphography,microscopy and confocal microscopy.Results STS angiosarcomas present heterogenous morphology with areas dominated by hemangiosarcoma and lymphangiosarcoma structures.STS angiosarcoma expressed phenotypes of both blood and lymphatic endothelia.LYVE-1 and VEGF-C is expressed by STS angiosarcoma and may be used to discriminate tumour differentiation.Morphology of lymphatic vessels and spaces in the tumour suggest absence of their normal lymphatic function.Conclusions Our results confirmed both hemangio-and lymphangiogenic origin of STS angiosarcoma

  20. Anatomy of the lymphatics.

    Science.gov (United States)

    Skandalakis, John E; Skandalakis, Lee J; Skandalakis, Panagiotis N

    2007-01-01

    The lymphatic system is perhaps the most complicated system of Homo sapiens. An introduction to the anatomy, embryology, and anomalies of the lymphatics is presented. The overall anatomy and drainage of the lymphatic vessels in outlined. The topographic anatomy, relations, and variations of the principle vessels of the lymphatic system (the right lymphatic duct, the thoracic duct, and the cisterna chyli) are presented in detail.

  1. [The indicators of alteration of functional activity of vessel wall as new diagnostic criteria of development of initial stages of chronic lymphatic leukemia].

    Science.gov (United States)

    Jevak, T N; Chesnokova, N P; Shelekhova, T I

    2015-03-01

    The role of endothelium dysfunction in pathogenesis of B-cell mode of chronic lymphatic leukemia is still uncovered. However, detection of disorders of functional activity of vessel wall at early stages of development of this disease permits to widen actual diagnostic criteria of its initiation and thereafter to make more objective diagnostic itself. The study was targeted to establish the role of endothelium dysfunction in pathogenesis of initial stages (0-1 stages according classification Rai K. et al. 1975) of B-cell mode of chronic lymphatic leukemia. The article presents results of clinical laboratory examination of 30 patients with initial stages of B-cell mode of chronic lymphatic leukemia. The content of classic markers of endothelium dysfunction in blood serum were detected using one time solid-phase enzymoimmunoassay at the moment of admission to hospital before initiation of treatment. In patients with chronic lymphatic leukemia blood serum characterized by increasing of level of E-selectin. ICAM-1, endothelin-1, metabolites of nitrogen nitrite, angiotensin II. At the same time, content of protein C decreased at the stage 0-1 of mentioned pathology. Hence, it is recommended to apply determining in blood serum the content of markers of endothelium dysfunction as additional diagnostic criteria of development of paraneoplastic disorders at initial stages of chronic lymphatic leukemia. These markers include molecules of adhesion (E-selectin, ICAM-I), metabolites of nitrogen nitrite, endothelin-1, protein C. angiotensin II and homocysteine.

  2. Lymphatic fluid: exchange mechanisms and regulation

    Science.gov (United States)

    Huxley, Virginia H; Scallan, Joshua

    2011-01-01

    Abstract Regulation of fluid and material movement between the vascular space of microvessels penetrating functioning organs and the cells therein has been studied extensively. Unanswered questions as to the regulatory mechanisms and routes remain. Significantly less is known about the lymphatic vascular system given the difficulties in seeing, no less isolating, these vessels lying deeper in these same tissues. It has become evident that the exchange microvasculature is not simply a passive biophysical barrier separating the vascular and interstitial compartments but a dynamic, multicellular structure subject to acute regulation and chronic adaptation to stimuli including inflammation, sepsis, diabetes, injury, hypoxia and exercise. Similarly lymphatic vessels range, in their simplest form, from lymphatic endothelium attached to the interstitial matrix, to endothelia and phasic lymphatic smooth muscle that act as Starling resistors. Recent work has demonstrated that among the microvascular lymphatic elements, the collecting lymphatics have barrier properties similar to venules, and thus participate in exchange. As with venules, vasoactive agents can alter both the permeability and contractile properties thereby setting up previously unanticipated gradients in the tissue space and providing potential targets for the pharmacological prevention and/or resolution of oedema. PMID:21521763

  3. Exercise training improves obesity‐related lymphatic dysfunction

    Science.gov (United States)

    Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; García Nores, Gabriela D.; Torrisi, Jeremy S.; Nitti, Matthew D.; Gardenier, Jason C.; Zhou, Jie; Yu, Jessie Z.; Jones, Lee W.

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction.Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells.Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic

  4. Exercise training improves obesity-related lymphatic dysfunction.

    Science.gov (United States)

    Hespe, Geoffrey E; Kataru, Raghu P; Savetsky, Ira L; García Nores, Gabriela D; Torrisi, Jeremy S; Nitti, Matthew D; Gardenier, Jason C; Zhou, Jie; Yu, Jessie Z; Jones, Lee W; Mehrara, Babak J

    2016-08-01

    Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti-inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic

  5. Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development.

    Science.gov (United States)

    Swartley, Olivia M; Foley, Julie F; Livingston, David P; Cullen, John M; Elmore, Susan A

    2016-07-01

    A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular development is dependent upon normal vasculogenesis, angiogenesis, and the transformation of vessels into their adult counterparts. Any alteration in vascular development has the potential to cause deformities or embryonic death. Numerous publications describe specific stages of vascular development relating to various organs, but a single resource detailing the stage-by-stage development of the vasculature pertaining to the hepatobiliary system has not been available. This comprehensive histology atlas provides hematoxylin & eosin and immunohistochemical-stained sections of the developing mouse blood and lymphatic vasculature with emphasis on the hepatobiliary system between embryonic days (E) 11.5-18.5 and the early postnatal period. Additionally, this atlas includes a 3-dimensional video representation of the E18.5 mouse venous vasculature. One of the most noteworthy findings of this atlas is the identification of the portal sinus within the mouse, which has been erroneously misinterpreted as the ductus venosus in previous publications. Although the primary purpose of this atlas is to identify normal hepatobiliary vascular development, potential embryonic abnormalities are also described. © The Author(s) 2016.

  6. The evolution of development of vascular cambia and secondary growth

    Science.gov (United States)

    Andrew Groover; Rachel Spicer

    2010-01-01

    Secondary growth from vascular cambia results in radial, woody growth of stems. The innovation of secondary vascular development during plant evolution allowed the production of novel plant forms ranging from massive forest trees to flexible, woody lianas. We present examples of the extensive phylogenetic variation in secondary vascular growth and discuss current...

  7. Novel characterization of lymphatic valve formation during corneal inflammation.

    Directory of Open Access Journals (Sweden)

    Tan Truong

    Full Text Available Lymphatic research has progressed rapidly in recent years. Though lymphatic dysfunction has been found in a wide array of disorders from transplant rejection to cancer metastasis, to date, there is still little effective treatment for lymphatic diseases. The cornea offers an optimal site for lymphatic research due to its accessible location, transparent nature, and lymphatic-free but inducible features. However, it still remains unknown whether lymphatic valves exist in newly formed lymphatic vessels in the cornea, and how this relates to an inflammatory response. In this study, we provide the first evidence showing that lymphatic valves were formed in mouse cornea during suture-induced inflammation with the up-regulation of integrin alpha 9. The number of corneal valves increased with the progression of inflammatory lymphangiogenesis. Moreover, we have detected lymphatic valves at various developmental stages, from incomplete to more developed ones. In addition to defining the average diameter of lymphatic vessels equipped with lymphatic valves, we also report that lymphatic valves were more often located near the branching points. Taken together, these novel findings not only provide new insights into corneal lymphatic formation and maturation, but also identify a new model for future investigation on lymphatic valve formation and possibly therapeutic intervention.

  8. [DEVELOPMENT OF CELL SHEET ENGINEERING TECHNOLOGY IN ENGINEERING VASCULARIZED TISSUE].

    Science.gov (United States)

    Chen, Jia; Ma, Dongyang; Ren, Liling

    2015-03-01

    To review the development of cell sheet engineering technology in engineering vascularized tissue. The literature about cell sheet engineering technology and engineering vascularized tissue was reviewed, analyzed, and summarized. Although there are many methods to engineer vascularized tissue, cell sheet engineering technology provides a promising potential to develop a vascularized tissue. Recently, cell sheet engineering technology has become a hot topic in engineering vascularized tissue. Co-culturing endothelial cells on a cell sheet, endothelial cells are able to form three-dimensional prevascularized networks and microvascular cavities in the cell sheet, which facilitate the formation of functional vascular networks in the transplanted tissue. Cell sheet engineering technology is a promising strategy to engineer vascularized tissue, which is still being studied to explore more potential.

  9. Pediatric lymphatic malformations: evolving understanding and therapeutic options.

    Science.gov (United States)

    Defnet, Ann M; Bagrodia, Naina; Hernandez, Sonia L; Gwilliam, Natalie; Kandel, Jessica J

    2016-05-01

    Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, along with knowledge gained from clinical practice. A patient-centered approach, ideally provided by a multidisciplinary medical and surgical team, should guide timing and modality of treatment. Current treatment options include observation, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New medical and surgical therapies are emerging, and include sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management is to support and optimize these patients' quality of life. Researchers continue to study lymphatic malformations with the goal of increasing therapeutic options and developing effective clinical pathways for these complicated lesions.

  10. Plant vascular development: from early specification to differentiation.

    Science.gov (United States)

    De Rybel, Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate plant vascular development. Using Arabidopsis thaliana as a model system, these studies enable the description of vascular development from the earliest tissue specification events during embryogenesis to the differentiation of phloem and xylem tissues. Moreover, we propose a model for how oriented cell divisions give rise to a three-dimensional vascular bundle within the root meristem.

  11. Angiogenesis: the genetic regulation of vascular development

    NARCIS (Netherlands)

    R.A. Haasdijk (Remco Anton)

    2014-01-01

    markdownabstract__Abstract__ For centuries, many scientists are fascinated by the organisation of the vascular network. The Greek philosopher and polymath Aristotle (384 BC) was one of the first man who described the vasculature. He wrote: “the system of blood vessels in the body may be compared to

  12. Lymphatic drainage of the liver and its implications in the management of colorectal cancer liver metastases.

    Science.gov (United States)

    Lupinacci, Renato Micelli; Paye, François; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Herman, Paulo

    2014-12-01

    The liver is the most common site of distant metastases in patients with colorectal cancer. Surgery represents the mainstream for curative treatment of colorectal cancer liver metastases (CRCLM) with long-term survival up to 58 and 36 % at 5 and 10 years, respectively. Despite advances on diagnosis, staging and surgical strategies, 60-70 % of patients will develop recurrence of the disease even after R0 resection of CRCLM. Tumor staging, prognosis, and therapeutic approaches for cancer are most often based on the extent of involvement of regional lymph nodes (LNs) and, to a lesser extent, on the invasion of regional lymphatic vessels draining the primary tumor. For CRCLM, the presence of intra hepatic lymphatic and blood vascular dissemination has been associated with an increased risk of intra hepatic recurrence, poorer disease-free and overall survival after liver resection. Also, several studies have reviewed the role of surgery in the patient with concomitant CRCLM and liver pedicle LN metastasis. Although pedicle LN involvement is related to worst survival rates, it does not differentiate patients that will relapse from those that will not. This review aims to briefly describe the anatomy of the liver's lymphatic drainage, the incidence of intrahepatic lymphatic invasion and hilar lymph node involvement, as well as their clinical impact in CRCLM. A better understanding of the role of liver lymphatic metastasis might, in the near future, impact the strategy of systemic therapies after liver resection as for primary colorectal tumors.

  13. In vivo determination of collecting lymphatic vessel permeability to albumin: a role for lymphatics in exchange

    Science.gov (United States)

    Scallan, Joshua P; Huxley, Virginia H

    2010-01-01

    While it is well established that the lymphatic vasculature is central to fluid and solute homeostasis, how it accomplishes this task is not well defined. To clarify the basic mechanisms underlying basal fluid and solute homeostasis, we assessed permeability to rat serum albumin () in mesenteric collecting lymphatic vessels and venules of juvenile male rats. Using the quantitative microfluorometric technique originally developed for blood capillaries, we tested the hypothesis that as a consequence of venules and collecting lymphatics sharing a common embryological origin, their would not differ significantly. Supporting our hypothesis, the median collecting lymphatic (3.5 ± 1.0 × 10−7 cm s−1, N= 22) did not differ significantly from the median venular (4.0 ± 1.0 × 10−7 cm s−1, N= 8, P= 0.61). For collecting lymphatics the diffusive permeability (Pd= 2.5 × 10−7 cm s−1) was obtained from the relationship of apparent and pressure. While the measured , Pd and estimated hydraulic conductivity of collecting lymphatics and venules were similar, the contribution of convective coupling differs as a result of the higher hydrostatic pressure experienced by venules relative to collecting lymphatics in vivo. In summary, the data demonstrate the capacity for collecting lymphatics to act as exchange vessels, able to extravasate solute and filter fluid. As a consequence these data provide experimental support for the theory that prenodal lymphatic vessels concentrate intraluminal protein. PMID:19917564

  14. Lymphangiogenesis by blind-ended vessel sprouting is concurrent with hemangiogenesis by vascular splitting.

    Science.gov (United States)

    Parsons-Wingerter, Patricia; McKay, Terri L; Leontiev, Dmitry; Vickerman, Mary B; Condrich, Terence K; Dicorleto, Paul E

    2006-03-01

    Development of effective vascular therapies requires the understanding of all modes of vessel formation involved in angiogenesis (here termed "hemangiogenesis") and lymphangiogenesis. Two major modes of vessel morphogenesis include sprouting of a new vessel from a preexisting vessel and splitting of a preexisting parent vessel into two offspring vessels. In the quail chorioallantoic membrane (CAM) during mid-development (embryonic days E6-E9), lymphangiogenesis progressed primarily via blind-ended vessel sprouting. Isolated lymphatic endothelial progenitor cells were recruited to the tips of growing vessels. During concurrent hemangiogenesis, parent blood vessels expanded from the capillary network and split into offspring vessels, accompanied by transient capillary expression of alpha smooth muscle actin (alphaSMA) and recruitment of polarized mural progenitor cells. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptor VEGFR-2, alphaSMA (specific to CAM blood vessels), homeobox transcription factor Prox1 (specific to lymphatics), and the quail hematopoetic marker, QH-1. VEGFR-2 was expressed intensely in isolated cells and lymphatics, and moderately in blood vessels. Prox1 was absent from isolated progenitor cells prior to lymphatic recruitment. Exogenous vascular endothelial growth factor-165 (VEGF165) increased blood vessel density and anastomotic frequency without changing endogenous modes of vascular/lymphatic vessel formation or marker expression. Although VEGF165 is a key cellular regulator of hemangiogenesis and vasculogenesis, the role of VEGF165 in lymphangiogenesis is less clear. Interestingly, VEGF165 increased lymphatic vessel diameter and density as measured by novel Euclidean distance mapping, and the antimaturational dissociation of lymphatics from blood vessels, accompanied by lymphatic reassociation into homogeneous networks.

  15. Cell-free vascular grafts: Recent developments and clinical potential.

    Science.gov (United States)

    Row, Sindhu; Santandreu, Ana; Swartz, Daniel D; Andreadis, Stelios T

    2017-03-01

    Recent advances in vascular tissue engineering have led to the development of cell-free grafts that are available off-the-shelf for on demand surgery. Challenges associated with cell-based technologies including cell sourcing, cell expansion and long-term bioreactor culture motivated the development of completely cell-free vascular grafts. These are based on decellularized arteries, decellularized cultured cell-based tissue engineered grafts or biomaterials functionalized with biological signals that promote in situ tissue regeneration. Clinical trials undertaken to demonstrate the applicability of these grafts are also discussed. This comprehensive review summarizes recent developments in vascular graft technologies, with potential applications in coronary artery bypass procedures, lower extremity bypass, vascular injury and trauma, congenital heart diseases and dialysis access shunts, to name a few.

  16. Ftr82 Is Critical for Vascular Patterning during Zebrafish Development

    Directory of Open Access Journals (Sweden)

    Hsueh-Wei Chang

    2017-01-01

    Full Text Available Cellular components and signaling pathways are required for the proper growth of blood vessels. Here, we report for the first time that a teleost-specific gene ftr82 (finTRIM family, member 82 plays a critical role in vasculature during zebrafish development. To date, there has been no description of tripartite motif proteins (TRIM in vascular development, and the role of ftr82 is unknown. In this study, we found that ftr82 mRNA is expressed during the development of vessels, and loss of ftr82 by morpholino (MO knockdown impairs the growth of intersegmental vessels (ISV and caudal vein plexus (CVP, suggesting that ftr82 plays a critical role in promoting ISV and CVP growth. We showed the specificity of ftr82 MO by analyzing ftr82 expression products and expressing ftr82 mRNA to rescue ftr82 morphants. We further showed that the knockdown of ftr82 reduced ISV cell numbers, suggesting that the growth impairment of vessels is likely due to a decrease of cell proliferation and migration, but not cell death. In addition, loss of ftr82 affects the expression of vascular markers, which is consistent with the defect of vascular growth. Finally, we showed that ftr82 likely interacts with vascular endothelial growth factor (VEGF and Notch signaling. Together, we identify teleost-specific ftr82 as a vascular gene that plays an important role for vascular development in zebrafish.

  17. Molecular mechanisms for vascular development and secondary cell wall formation

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    Jung Hyun eYang

    2016-03-01

    Full Text Available Vascular tissues are important for transporting water and nutrients throughout the plant and as physical support of upright growth. The primary constituents of vascular tissues, xylem and phloem, are derived from the meristematic vascular procambium and cambium. Xylem cells develop secondary cell walls that form the largest part of plant lignocellulosic biomass that serve as a renewable feedstock for biofuel production. For the last decade, research on vascular development and secondary cell wall biosynthesis has seen rapid progress due to the importance of these processes to plant biology and to the biofuel industry. Plant hormones, transcriptional regulators and peptide signaling regulate procambium/cambium proliferation, vascular patterning, and xylem differentiation. Transcriptional regulatory pathways play a pivot role in secondary cell wall biosynthesis. Although most of these discoveries are derived from research in Arabidopsis, many genes have shown conserved functions in biofuel feedstock species. Here, we review the recent advances in our understanding of vascular development and secondary cell wall formation and discuss potential biotechnological uses.

  18. Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity.

    Science.gov (United States)

    Savetsky, Ira L; Albano, Nicholas J; Cuzzone, Daniel A; Gardenier, Jason C; Torrisi, Jeremy S; García Nores, Gabriela D; Nitti, Matthew D; Hespe, Geoffrey E; Nelson, Tyler S; Kataru, Raghu P; Dixon, J Brandon; Mehrara, Babak J

    2015-11-01

    Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C-C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response.

  19. Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

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    Philipp Steven

    Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

  20. The development of the vascular system: a historical overview.

    Science.gov (United States)

    Ribatti, Domenico; Nico, Beatrice; Crivellato, Enrico

    2015-01-01

    Development of the vascular system involves a complex sequence of inductive and differentiating signals leading to vasculogenesis and/or angiogenesis. Dissecting and exploring this process in its multifaceted morphological and molecular aspects has represented a basic contribution and a fascinating adventure in the history of biology. Vasculogenesis, that is de novo formation of vascular channels, initiates early during embryo development and prevails at the beginning of embryo patterning and organ formation. Angiogenesis, the process of shaping new vessels from preexisting blood vessels, mainly operates during postnatal life. In this historical introduction, we try to retrace the early steps of scientific speculation on vascular development and to recapitulate the principal paths leading to our present appreciation of blood vessel formation.

  1. Advances in Lymphatic Imaging and Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nune, Satish K.; Gunda, Padmaja; Majeti, Bharat K.; Thallapally, Praveen K.; Laird, Forrest M.

    2011-09-10

    Cancer remains the second leading cause of death after heart disease in the US. While metastasized cancers such as breast, prostate, and colon are incurable, before their distant spread, these diseases will have invaded the lymphatic system as a first step in their progression. Hence, proper evaluation of the disease state of the lymphatics which drain a tumor site is crucial to staging and the formation of a treatment plan. Current lymphatic imaging modalities with visible dyes and radionucleotide tracers offer limited sensitivity and poor resolution; however, newer tools using nanocarriers, quantum dots, and magnetic resonance imaging promise to vastly improve the staging of lymphatic spread without needless biopsies. Concurrent with the improvement of lymphatic imaging agents, has been the development of drug carriers that can localize chemotherapy to the lymphatic system, thus improving the treatment of localized disease while minimizing the exposure of healthy organs to cytotoxic drugs. This review will focus on polymeric systems that have been developed for imaging and drug delivery to the lymph system, how these new devices improve upon current technologies, and where further improvement is needed.

  2. Laminar flow downregulates Notch activity to promote lymphatic sprouting.

    Science.gov (United States)

    Choi, Dongwon; Park, Eunkyung; Jung, Eunson; Seong, Young Jin; Yoo, Jaehyuk; Lee, Esak; Hong, Mingu; Lee, Sunju; Ishida, Hiroaki; Burford, James; Peti-Peterdi, Janos; Adams, Ralf H; Srikanth, Sonal; Gwack, Yousang; Chen, Christopher S; Vogel, Hans J; Koh, Chester J; Wong, Alex K; Hong, Young-Kwon

    2017-04-03

    The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.

  3. The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

    Science.gov (United States)

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-09-01

    In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

  4. Reactive Oxygen Species in Vascular Formation and Development

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    Yijiang Zhou

    2013-01-01

    Full Text Available Reactive oxygen species (ROS are derived from the metabolism of oxygen and are traditionally viewed as toxic byproducts that cause damage to biomolecules. It is now becoming widely acknowledged that ROS are key modulators in a variety of biological processes and pathological states. ROS mediate key signaling transduction pathways by reversible oxidation of certain signaling components and are involved in the signaling of growth factors, G-protein-coupled receptors, Notch, and Wnt and its downstream cascades including MAPK, JAK-STAT, NF-κB, and PI3K/AKT. Vascular formation and development is one of the most important events during embryogenesis and is vital for postnasal tissue repair. In this paper, we will discuss how ROS regulate different steps in vascular development, including smooth muscle cell differentiation, angiogenesis, endothelial progenitor cells recruitment, and vascular cell migration.

  5. Comparative and Developmental Anatomy of Cardiac Lymphatics

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    A. Ratajska

    2014-01-01

    Full Text Available The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

  6. Comparative and Developmental Anatomy of Cardiac Lymphatics

    Science.gov (United States)

    Ratajska, A.; Gula, G.; Flaht-Zabost, A.; Czarnowska, E.; Ciszek, B.; Jankowska-Steifer, E.; Niderla-Bielinska, J.; Radomska-Lesniewska, D.

    2014-01-01

    The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells. PMID:24592145

  7. Evaluation of lymphatic regeneration in rat incisional wound healing and its use in wound age estimation

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    Nevine M.F. El Deeb

    2015-03-01

    Conclusion: Lymphatic elements appear transiently in the wound edge, concurrent with the appearance of blood vessels but regress earlier. Identification of lymphatic vascular channels in the region of the wound may help to estimate the wound age in the early days after the injury. At later time points in the regeneration process, it may help to recognize the injured area, being the area where the dermis and subcutaneous tissue are devoid of lymphatics.

  8. The plant vascular system: Evolution, development and functions

    Science.gov (United States)

    William J. Lucas; Andrew Groover; Raffael Lichtenberger; Kaori Furuta; Shri-Ram Yadav; Yka Helariutta; Xin-Qiang He; Hiroo Fukuda; Julie Kang; Siobhan M. Brady; John W. Patrick; John Sperry; Akiko Yoshida; Ana-Flor Lopez-Millan; Michael A. Grusak; Pradeep Kachroo

    2013-01-01

    The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made...

  9. The Plant Vascular System: Evolution, Development and Functions

    Institute of Scientific and Technical Information of China (English)

    William J.Lucas; Andrew Groover; Raffael Lichtenberger; Kaori Furuta; Shri-Ram Yadav; Yk(a) Helariutta; Xin-Qiang He

    2013-01-01

    The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology,in general,through its role in facilitating the development of plants with increased stature,photosynthetic output,and ability to colonize a greatly expanded range of environmental habitats.Recently,considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system.In this review,we first examine the evolutionary events that gave rise to the tracheophytes,followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms.The two essential functions performed by the vascular system,namely the delivery of resources (water,essential mineral nutrients,sugars and amino acids) to the various plant organs and provision of mechanical support are next discussed.Here,we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem.Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental,physiological and defense-related processes,at the whole-plant level.A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology.Finally,areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.

  10. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Miyashita, Takenori, E-mail: takenori@med.kagawa-u.ac.jp [Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793 (Japan); Burford, James L. [Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Hong, Young-Kwon [Department of Surgery and Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Gevorgyan, Haykanush; Lam, Lisa [Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Mori, Nozomu [Department of Otolaryngology, Faculty of Medicine, Kagawa University, Kagawa 761-0793 (Japan); Peti-Peterdi, Janos [Department of Physiology and Biophysics and Department of Medicine, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)

    2013-10-25

    Highlights: •We newly developed the whole-mount imaging method of the tympanic membrane. •Lymphatic vessel loops were localized around the malleus handle and annulus tympanicus. •In regeneration, abundant lymphatic vessels were observed in the pars tensa. •Site-specific lymphatic vessels may play an important role in the tympanic membrane. -- Abstract: We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane.

  11. Intensity and efficiency of transmission and the development of microfilaraemia and disease: their relationship in lymphatic filariasis.

    Science.gov (United States)

    Southgate, B A

    1992-02-01

    Currently available methods for measuring the intensity of transmission in the lymphatic filariases are all to some extent unsatisfactory. Clinical methods for defining the presence of filarial disease are also less than perfect, and many infected persons remain free of symptoms and signs for very long periods. Incidence rates of microfilaraemia calculated from prevalence rate data are combined with 'entomological inoculation rates' obtained by direct observations of vector landing rates, infective larval rates and infective larval densities in field studies to determine efficiencies of transmission, and to relate transmission parameters to observed microfilarial and disease prevalence rates. Published studies from various endemic areas of the world which provide sufficient data have been analysed, using reversible catalytic models. In general, it seems that much less intense levels of transmission are needed in sub-Saharan Africa to produce given rates of microfilaraemia and disease than in Asia and Oceania, in the case of Wuchereria bancrofti infections; similarly, the genus Anopheles appears to produce infection and disease much more efficiently than the genera Culex and Aedes when transmitting W. bancrofti. The only example of Brugia malayi transmitted by Mansonia spp. analysed provided the highest level of transmission efficiency found. Tolerable levels of transmission analogous to those used in onchocerciasis cannot at present be defined for the lymphatic filariases; it seems that the intensity of transmission required to produce new cases of disease is probably below that required to produce new cases or episodes of readily detectable microfilaraemia.

  12. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

    NARCIS (Netherlands)

    J. Bussmann (Jeroen); F.L. Bos (Frank); A. Urasaki (Akihiro); K. Kawakami (Koichi); H.J. Duckers (Henricus); S. Schulte-Merker (Stefan)

    2010-01-01

    textabstractThe endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk

  13. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

    NARCIS (Netherlands)

    Bussmann, J.; Bos, F.L.; Urasaki, A.; Kawakami, K.; Duckers, H.J.; Schulte-Merker, S.

    2010-01-01

    The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk consisting of

  14. Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

    NARCIS (Netherlands)

    J. Bussmann (Jeroen); F.L. Bos (Frank); A. Urasaki (Akihiro); K. Kawakami (Koichi); H.J. Duckers (Henricus); S. Schulte-Merker (Stefan)

    2010-01-01

    textabstractThe endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk co

  15. Recent advances in the research of lymphatic stomata.

    Science.gov (United States)

    Wang, Zi-Bin; Li, Meng; Li, Ji-Cheng

    2010-05-01

    Lymphatic stomata are small openings of lymphatic capillaries on the free surface of the mesothelium. The peritoneal cavity, pleural cavity, and pericardial cavity are connected with lymphatic system via these small openings, which have the function of active absorption. The ultrastructure of the lymphatic stomata and their absorption from the body cavities are important clinically, such as ascites elimination, neoplasm metastasis, and inflammatory reaction. The lymphatic stomata play an important role in the physiological and pathological conditions. Our previous study indicated for the first time that nitric oxide (NO) could regulate the opening and absorption of the lymphatic stomata. It could decrease the level of free intracellular calcium [Ca(2+)] through increasing the cyclic guanosine monophosphate (cGMP) level in the rat peritoneal mesothelial cells, thus regulating the lymphatic stomata. This process is related with the NO-cGMP-[Ca(2+)] signal pathway. In this review, we summarize the recent advances in understanding the development and the function of the lymphatic stomata. The ultrastructure and regulations of the lymphatic stomata are also discussed in this review.

  16. Quantification of blood flow and topology in developing vascular networks.

    Directory of Open Access Journals (Sweden)

    Astrid Kloosterman

    Full Text Available Since fluid dynamics plays a critical role in vascular remodeling, quantification of the hemodynamics is crucial to gain more insight into this complex process. Better understanding of vascular development can improve prediction of the process, and may eventually even be used to influence the vascular structure. In this study, a methodology to quantify hemodynamics and network structure of developing vascular networks is described. The hemodynamic parameters and topology are derived from detailed local blood flow velocities, obtained by in vivo micro-PIV measurements. The use of such detailed flow measurements is shown to be essential, as blood vessels with a similar diameter can have a large variation in flow rate. Measurements are performed in the yolk sacs of seven chicken embryos at two developmental stages between HH 13+ and 17+. A large range of flow velocities (1 µm/s to 1 mm/s is measured in blood vessels with diameters in the range of 25-500 µm. The quality of the data sets is investigated by verifying the flow balances in the branching points. This shows that the quality of the data sets of the seven embryos is comparable for all stages observed, and the data is suitable for further analysis with known accuracy. When comparing two subsequently characterized networks of the same embryo, vascular remodeling is observed in all seven networks. However, the character of remodeling in the seven embryos differs and can be non-intuitive, which confirms the necessity of quantification. To illustrate the potential of the data, we present a preliminary quantitative study of key network topology parameters and we compare these with theoretical design rules.

  17. Lymphatic compensation during the postoperative period after breast cancer treatment with axillary dissection

    Directory of Open Access Journals (Sweden)

    Mariana Maia Freire de Oliveira

    2015-06-01

    Full Text Available Lymphedema secondary to breast cancer causes physical and psychological morbidity and compromises quality of life. The objective of this literature review was to study lymphatic compensation after surgery for breast cancer and the factors that influence this process, with a view to understanding the etiopathogenesis of lymphedema. Articles indexed on Pubmed published from 1985 to 2012 were reviewed. According to the literature, lymphangiogenesis reduces damage to lymph vessels; there is little evidence that Vascular Endothelial Growth Factor is elevated in women with lymphedema; lymphovenous communications can be observed 60 days after surgery; women without lymphedema have acquired alternative mechanisms for removal of proteins from the interstitial space; and active exercise stimulates lymphatic and venous pumping. Health professionals should teach these patients about the risk factors for lymphedema. The effects of lymphangiogenesis, proteolysis and lymphovenous communications on development of lymphedema should be studied, since these events are intimately related.

  18. Rho kinase enhances contractions of rat mesenteric collecting lymphatics.

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    Kristine H Kurtz

    Full Text Available The mechanisms that control phasic and tonic contractions of lymphatic vessels are poorly understood. We hypothesized that rho kinase ROCK, previously shown to increase calcium (Ca2+ sensitivity in vascular smooth muscle, enhances lymphatic contractile activity in a similar fashion. Contractions of isolated rat mesenteric lymphatic vessels were observed at a luminal pressure of 2 cm H2O in a 37°C bath. The expression of ROCK in isolated rat mesenteric lymphatic vessels was assessed by Western blotting and confocal microscopy. The role of ROCK in contractile function was tested using two specific yet structurally distinct inhibitors: H1152 (0.1-10 μM and Y-27632 (0.5-50 μM. In addition, lymphatics were transfected with constitutively active (ca-ROCK protein (2 μg/ml to assess gain of contractile function. Vessel diameter and the concentration of intracellular free Ca2+ ([Ca2+]i were simultaneously measured in a subset of isolated lymphatics loaded with the Ca2+-sensing dye fura-2. The results show expression of both the ROCK1 and ROCK2 isoforms in lymphatic vessels. Inhibition of ROCK increased lymphatic end diastolic diameter and end systolic diameter in a concentration-dependent manner. Significant reductions in lymphatic tone and contraction amplitude were observed after treatment 1-10 μM H1152 or 25-50 μM Y-27632. H1152 (10 μM also significantly reduced contraction frequency. Transient increases in [Ca2+]i preceded each phasic contraction, however this pattern was disrupted by either 10 μM H1152 or 50 μM Y-27632 in the majority of lymphatics studied. The significant decrease in tone caused by H1152 or Y-27632 was not associated with a significant change in the basal [Ca2+]i between transients. Transfection with ca-ROCK protein enhanced lymphatic tone, but was not associated with a significant change in basal [Ca2+]i. Our data suggest that ROCK mediates normal tonic constriction and influences phasic contractions in lymphatics. We

  19. ENDOMETRIOSIS WITH LYMPHATIC SPREAD

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    Narmadha

    2014-10-01

    Full Text Available Pelvic endometriosis is a common gynaecologic problem. But the histogenesis of endometriosis was not so clear. Various theories have been proposed by Pathologist in the past. Here we present a case of endometriosis of fallopian tube by lymphatic spread which has been proved histopathologically

  20. Recent advances in lymphatic targeted drug deliver y system for tumor metastasis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Zhang; Wei-Yue Lu

    2014-01-01

    Te lymphatic system has an important defensive role in the human body. hTe metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors;the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the speciifcity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

  1. Uteroplacental circulation and fetal vascular function and development.

    Science.gov (United States)

    Thornburg, Kent L; Louey, Samantha

    2013-09-01

    Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

  2. Systematic development of solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the oral bioavailability and intestinal lymphatic uptake of lopinavir.

    Science.gov (United States)

    Garg, Babita; Katare, O P; Beg, Sarwar; Lohan, Shikha; Singh, Bhupinder

    2016-05-01

    The present studies entail the development of the systematically optimized solid self-nanoemulsifying oily formulations (S-SNEOFs) for enhancing the systemic bioavailability of lopinavir and targeting the same to the sanctuary site, i.e., lymphatic system for complete HIV inhibition. The patient-centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through failure mode and effect critically analysis (FMECA), helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. As per the preliminary studies, viz solubility and phase titration studies, and factor screening studies, Maisine (i.e., lipid), Tween 80 (emulgent), Transcutol HP (i.e., cosolvent) were selected as the critical material attributes (CMAs) of the liquid SNEOFs (L-SNEOFs). D-optimal mixture design was employed for the optimization of aforesaid CMAs and evaluated for in vitro dissolution, globule size, ex vivo permeation studies as the critical quality attributes (CQAs). Optimal composition of CMAs, was embarked through numerical optimization and desirability function, exhibited excellent permeation and drug release characteristics besides possessing globule size in nano range, i.e., 53.16 nm. Further to increase the stability and drug loading, the OPT-L-SNEOFs were then adsorbed onto the porous carrier, i.e., Aeroperl, to prepare the OPT-SNEOF tablets which were finally compressed into the tablet employing MCC as the filler. The performance evaluation through in situ SPIP studies ascribed the significant enhancement in absorptivity parameters of both the SNEOFs vis-à-vis the pure drug. Also, chylomicron flow block SPIP studies revealed lymphatic uptake of lopinavir from the SNEOFs. Overall, in vivo pharmacokinetic studies in rats revealed significant improvement in the rate and extent of oral bioavailability of the SNEOFs compared to the pure drug. These studies

  3. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We detail...

  4. Imaging vasculature and lymphatic flow in mice using quantum dots

    DEFF Research Database (Denmark)

    Ballou, Byron; Ernst, Lauren A.; Andreko, Susan

    2009-01-01

    Quantum dots are ideal probes for fluorescent imaging of vascular and lymphatic tissues. On injection into appropriate sites, red- and near-infrared-emitting quantum dots provide excellent definition of vasculature, lymphoid organs, and lymph nodes draining both normal tissues and tumors. We deta...

  5. The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel

    Science.gov (United States)

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-01-01

    In glaucoma, aqueous outflow into the Schlemm’s canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment. PMID:25061878

  6. Contemporary vascular smartphone medical applications.

    Science.gov (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

    2013-08-01

    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Follicular thyroid carcinoma invades venous rather than lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Liu Yulin

    2010-01-01

    Full Text Available Abstract Follicular thyroid carcinoma (FTC tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker, can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02. The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003. Fourteen of 32 (44% FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations.

  8. Podoplanin-Fc reduces lymphatic vessel formation in vitro and in vivo and causes disseminated intravascular coagulation when transgenically expressed in the skin.

    Science.gov (United States)

    Cueni, Leah N; Chen, Lu; Zhang, Hui; Marino, Daniela; Huggenberger, Reto; Alitalo, Annamari; Bianchi, Roberta; Detmar, Michael

    2010-11-18

    Podoplanin is a small transmembrane protein required for development and function of the lymphatic vascular system. To investigate the effects of interfering with its function, we produced an Fc fusion protein of its ectodomain. We found that podoplanin-Fc inhibited several functions of cultured lymphatic endothelial cells and also specifically suppressed lymphatic vessel growth, but not blood vessel growth, in mouse embryoid bodies in vitro and in mouse corneas in vivo. Using a keratin 14 expression cassette, we created transgenic mice that overexpressed podoplanin-Fc in the skin. No obvious outward phenotype was identified in these mice, but surprisingly, podoplanin-Fc-although produced specifically in the skin-entered the blood circulation and induced disseminated intravascular coagulation, characterized by microthrombi in most organs and by thrombocytopenia, occasionally leading to fatal hemorrhage. These findings reveal an important role of podoplanin in lymphatic vessel formation and indicate the potential of podoplanin-Fc as an inhibitor of lymphangiogenesis. These results also demonstrate the ability of podoplanin to induce platelet aggregation in vivo, which likely represents a major function of lymphatic endothelium. Finally, keratin 14 podoplanin-Fc mice represent a novel genetic animal model of disseminated intravascular coagulation.

  9. Morphogenesis, structure and properties of lymphatic vessels 

    Directory of Open Access Journals (Sweden)

    Anna Ratajska

    2012-11-01

    Full Text Available In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4 and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2. Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as

  10. Lymphatic malformations: a proposed management algorithm.

    LENUS (Irish Health Repository)

    Oosthuizen, J C

    2012-02-01

    OBJECTIVE: The aim of this study was to develop a management algorithm for cervicofacial lymphatic malformations, based on the authors\\' experience in managing these lesions as well as current literature on the subject. STUDY DESIGN AND METHODS: A retrospective medical record review of all the patients treated for lymphatic malformations at our institution during a 10-year period (1998-2008) was performed. DATA COLLECTED: age at diagnosis, location and type of lesion, radiologic investigation performed, presenting symptoms, treatment modality used, complications and results achieved. RESULTS: 14 patients were identified. Eight (57%) male and six (43%) female. There was an equal distribution between the left and right sides. The majority (71%) of cases were diagnosed within the first year of life. The majority of lesions were located in the suprahyoid region. The predominant reason for referral was an asymptomatic mass in 7 cases (50%) followed by airway compromise (36%) and dysphagia (14%). Management options employed included: observation, OK-432 injection, surgical excision and laser therapy. In 5 cases (36%) a combination of these were used. CONCLUSION: Historically surgical excision has been the management option of choice for lymphatic malformations. However due to the morbidity and high complication rate associated this is increasingly being questioned. Recent advances in sclerotherapy e.g. OK-432 injection have also shown significant promise. Based on experience in managing these lesions as well as current literature the authors of this paper have developed an algorithm for the management of cervicofacial lymphatic malformations.

  11. Endothelial-mural cell signaling in vascular development and angiogenesis.

    Science.gov (United States)

    Gaengel, Konstantin; Genové, Guillem; Armulik, Annika; Betsholtz, Christer

    2009-05-01

    Mural cells are essential components of blood vessels and are necessary for normal development, homeostasis, and organ function. Alterations in mural cell density or the stable attachment of mural cells to the endothelium is associated with several human diseases such as diabetic retinopathy, venous malformation, and hereditary stroke. In addition mural cells are implicated in regulating tumor growth and have thus been suggested as potential antiangiogenic targets in tumor therapy. In recent years our knowledge of mural cell function and endothelial-mural cell signaling has increased dramatically, and we now begin to understand the mechanistic basis of the key signaling pathways involved. This is mainly thanks to sophisticated in vivo experiments using a broad repertoire of genetic technologies. In this review, we summarize the five currently best understood signaling pathways implicated in mural cell biology. We discuss PDGFB/PDGFRbeta- dependent pericyte recruitment, as well as the role of angiopoietins and Tie receptors in vascular maturation. In addition, we highlight the effects of sphingosine-1-phosphate signaling on adherens junction assembly and vascular stability, as well as the role of TGF-beta-signaling in mural cell differentiation. We further reflect recent data suggesting an important function for Notch3 signaling in mural cell maturation.

  12. 基质细胞衍生因子-1α和白细胞介素-1β诱导淋巴管内皮表型的作用%Effect of stromal cell derived factor-1αand interleukin-1βon inducing vascular endothelial cells expressing lymphatic phenotype

    Institute of Scientific and Technical Information of China (English)

    索宁; 王雪颖; 杨春林; 周辉; 李菲; 张宗璞; 万芳竹; 田铧

    2014-01-01

    目的:探讨基质细胞衍生因子-1α( SDF-1α)及白细胞介素-1β( IL-1β)诱导内皮细胞表达淋巴管表型的作用。方法 SDF-1α和IL-1β分别诱导内皮细胞株CRL-1730,用Real-time PCR、Western blotting 及免疫细胞化学等方法检测其内皮及淋巴管标志物,的表达情况。结果 SDF-1α诱导培养之后,CRL-1730细胞株的内皮细胞标志物血管性血友病因子(vWF)、血管内皮钙黏蛋白(VE-cadherin)、血管内皮生长因子受体(VEGFR)2随其浓度增高而表达降低,淋巴管标志物平足蛋白( podoplanin )、同源异形盒蛋白-1( Prox-1)和淋巴管内皮透明质酸受体-1(LYVE-1)随其浓度增高而表达增高。 IL-1β诱导之后,CRL-1730细胞株的vWF、VEGFR2和podoplanin、prox-1、LYVE-1的变化趋势同SDF-1α,而VE-cadherin的表达量基本不变。结论 SDF-1α和IL-1β都能够诱导血管内皮细胞表达淋巴管标志物。%Objective To investigate the effect of stromal cell-derived factor-1α( SDF-1α) and interleukin ( IL-1β) on inducing vascular endothelial cells to express lymphatic phenotype .Methods The CRL-1730 cell line was cultured and treated with SDF-1αor IL-1β.The expression of endothelial cell markers and lymphatic endothelial cell markers were investigated with Real-time PCR, Western blotting and immunocytochemistry .Results In CRL-1730 cell line, endothelial cell markers such as voln willebrand factor ( vWF ) , VE-cadherin , vascular endothelial growth factor receptor(VEGFR)2, were dose dependently down-regulated after SDF-1αstimulation, while lymphatic phenotypes such as Prox-1, podoplanin and lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1), were dose-dependently up-regulated after SDF-1αstimulation.The changes of vWF, VEGFR2 and podoplanin, Prox-1, LYVE-1 expression after IL-1βstimulation was similar to that after SDF-1αwhile expression of VE-cadherin changed slightly .Conclusion SDF-1αand IL-1

  13. Synthesis of a novel polyamidoamine dendrimer conjugating with alkali blue as a lymphatic tracer and study on the lymphatic targeting in vivo.

    Science.gov (United States)

    Yang, Rui; Xia, Suxia; Ye, Tiantian; Yao, Jianhua; Zhang, Ruizhi; Wang, Shujun; Wang, Siling

    2016-09-01

    In this study, a novel lymphatic tracer polyamidoamin-alkali blue (PAMAM-AB) was synthesized in order to evaluate the intra-lymphatic targeting ability and lymphatic tropism of PAMAM-AB after subcutaneous administration. UV-Vis, FT-IR, NMR and HPLC characterization were performed to prove the successful synthesis of PAMAM-AB. The calculated AB payload of PAMAM-AB conjugate was seven per dendrimer molecule (27.16% by weight). Hydrolysis stability of PAMAM-AB in vitro was evaluated, which was stable in PBS and human plasma. Lymphatic tracing were studied to determine the blue-stained intensity of PAMAM-AB in right popliteral lymph nodes (PLNs), iliac lymph nodes (ILNs) and para-aortic lymph nodes (PALNs) after subcutaneous administration. The pharmacokinetics and biodistribution of PAMAM-AB in mice were investigated. PLNs, ILNs and PALNs could be obviously blue-stained within 10 min after PAMAM-AB administration, and displayed a more rapid lymphatic absorption, a higher AUC value in lymph nodes and a longer lymph nodes residence time compared with methylene blue solution (MB-S), MB water-in-oil microemulsion (MB-ME), MB multiple microemulsion (MB-MME). Enhanced lymphatic drainage from the injection site and uptake into lymph of PAMAM-AB indicated that PAMAM-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors or as a lymphatic tracer in its own right.

  14. Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance.

    Science.gov (United States)

    Mohammed, Rabab A A; Ellis, Ian O; Mahmmod, Ali M; Hawkes, E Claire; Green, Andrew R; Rakha, Emad A; Martin, Stewart G

    2011-06-01

    Basal and triple-negative breast cancer phenotypes are characterised by unfavourable biological behaviour and outcome. Although certain studies have examined their pathological and molecular profile, the vascular characteristics of lymphatic and blood vessels have not been examined. Immunohistochemical staining with podoplanin, CD34 and CD31 was used to examine lymphatic and microvessel density, as well as vascular invasion in 197 basal-like and in 99 triple-negative breast tumours and compared against 200 non-basal and 334 non-triple-negative cases. All specimens were lymph node negative. Vascular invasion was identified as blood or lymphatic vascular invasion by the differential expression of markers. All measurements were correlated with clinicopathological features and prognosis. No significant difference was detected between the basal and triple-negative groups in terms of lymphatic or microvessel density or vascular invasion. However, both the basal and the triple-negative groups showed significantly higher microvessel density than did the non-basal and non-triple-negative groups (P=0.017 and Pcontrols. Interestingly, vascular invasion, almost entirely lymphatic invasion, was detected in 27% of the basal and in 26% of the triple-negative groups with no significant difference in comparison with control groups. In both basal and triple negatives, vascular invasion was associated with poorer survival by univariate and multivariate analyses. The 20-year overall survival rate in basal-like tumours was 55% in vascular invasion-positive cases compared with 73% in vascular invasion-negative tumours (P=0.012), and 46% in triple-negative vascular invasion-positive compared with 79% in vascular invasion-negative tumours (P=0.001). Basal-like vs non-basal-like and triple-negative vs non-triple-negative tumours have similar vascular characteristics in terms of lymphatic vessel density and vascular invasion but higher microvessel density, suggesting that such groups may

  15. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2014-01-01

    Full Text Available Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review.

  16. Gorham-Stout disease and generalized lymphatic anomaly--clinical, radiologic, and histologic differentiation.

    Science.gov (United States)

    Lala, Shailee; Mulliken, John B; Alomari, Ahmad I; Fishman, Steven J; Kozakewich, Harry P; Chaudry, Gulraiz

    2013-07-01

    Gorham-Stout disease (GSD) is a rare vascular disorder of lymphatic origin characterized by progressive osteolysis. Generalized lymphatic anomaly (GLA) is a multisystem disorder that also commonly affects bone. We hypothesized that Gorham-Stout disease is different from other osseous lymphatic anomalies. We proposed to discriminate these entities by analyzing findings on skeletal imaging. Clinical data, imaging studies, and histopathologic findings were retrospectively reviewed in patients presenting to our Vascular Anomalies Center with lymphatic anomalies of bone. Within a cohort of 51 patients with lymphatic disorder and radiological evidence of bony involvement, two distinct categories emerged. Nineteen patients met the imaging criteria for GSD: progressive osteolysis with resorption and cortical loss. Thirty-two were categorized as GLA: Discrete radiolucencies and increasing numbers of bone affected over time, but without evidence of progressive osteolysis. The ribs were the most common site in both groups, followed by the cranium, clavicle, and cervical spine in GSD, and thoracic spine, humerus, and femur in GLA. Fewer bones were involved in GSD, with relative sparing of the appendicular skeleton. Associated infiltrative soft tissue abnormality was seen in 18 in GSD, but only six with GLA. Macrocystic lymphatic malformations were identified in 14 with GLA, but none with GSD. There are significant radiological differences between GSD and GLA, although there are some overlapping features. The major distinguishing characteristic is the progressive osteolysis seen in GSD. Findings suggestive of GLA are more extensive involvement, particularly of the appendicular skeleton, presence of discretemacrocystic lymphatic malformations and visceral organ lesions.

  17. Exercise training improves obesity‐related lymphatic dysfunction

    OpenAIRE

    2016-01-01

    Key points Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, imp...

  18. Immunohistochemical identification of lymphatic vessels in the periodontium of equine cheek teeth.

    Science.gov (United States)

    Staszyk, Carsten; Duesterdieck, Katja F; Gasse, Hagen; Bienert, Astrid

    2005-12-01

    Immunohistochemical detection of lymphatic capillaries was performed in the periodontium of maxillary and mandibular cheek teeth from 6 horses (aged 3-23 years). Tissue sections of the periodontium were taken at 4 different horizontal levels along the long axis of the tooth. The specimens were processed for immunoreaction with anti-Prox1, in order to distinguish lymphatic endothelium from blood vascular endothelium. Lymphatic vessels were detected in all periodontal tissues except for the dental cementum. Lymphatic capillaries were most densely distributed in the gingiva compared to other tissues of the periodontium. Lymphatic capillaries were found most consistently in samples taken from the gingival and subgingival regions in all horses examined. Within these levels, the gingiva as well as the spongiosa of the maxillary and mandibular bone had the greatest incidence of lymphatic vessels. Considering the distinct distribution of the lymphatic capillaries in the periodontium of the maxillary and mandibular cheek teeth, two complementary lymphatic drainage pathways are proposed: (1) superficial lymph drainage via the gingiva, emptying into the mandibular lymph nodes; (2) deep lymph drainage via the mandibular and maxillary spongiosa, emptying into the mandibular and retropharyngeal lymph nodes, respectively.

  19. Smooth muscle cell recruitment to lymphatic vessels requires PDGFB and impacts vessel size but not identity.

    Science.gov (United States)

    Wang, Yixin; Jin, Yi; Mäe, Maarja Andaloussi; Zhang, Yang; Ortsäter, Henrik; Betsholtz, Christer; Mäkinen, Taija; Jakobsson, Lars

    2017-08-29

    Tissue-fluid drains through blind-ended lymphatic capillaries, via smooth muscle cell (SMC)-covered collecting vessels into venous circulation. Both defective SMC recruitment to collecting vessels and ectopic recruitment to lymphatic capillaries are thought to contribute to vessel failure, leading to lymphedema. However, mechanisms controlling lymphatic SMC recruitment and their role in vessel maturation are unknown. Here we demonstrate that platelet-derived growth factor B (PDGFB) regulates lymphatic SMC recruitment in multiple vascular beds. PDGFB is selectively expressed by lymphatic endothelial cells (LECs) of collecting vessels. LEC-specific deletion of Pdgfb prevented SMC recruitment causing dilation and failure of pulsatile contraction of collecting vessels. However, vessel remodelling and identity were unaffected. Unexpectedly, PDGFB overexpression in LECs did not induce SMC recruitment to capillaries. This was explained by the demonstrated requirement of PDGFB extracellular matrix (ECM) retention for lymphatic SMC recruitment, and low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate a requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels and suggest an ECM-controlled checkpoint preventing SMC investment of capillaries, which is a common feature in lymphedematous skin. © 2017. Published by The Company of Biologists Ltd.

  20. The Development of Robotic Technology in Cardiac and Vascular Interventions

    National Research Council Canada - National Science Library

    Ali Pourdjabbar; Lawrence Ang; Ryan R. Reeves; Mitul P. Patel; Ehtisham Mahmud

    2017-01-01

    Robotic technology has been used in cardiovascular medicine for over a decade, and over that period its use has been expanded to interventional cardiology and percutaneous coronary and peripheral vascular interventions...

  1. Lymphatic Biodistribution of Polylactide Nanoparticles

    Science.gov (United States)

    Chaney, Eric J.; Tang, Li; Tong, Rong; Cheng, Jianjun; Boppart, Stephen A.

    2013-01-01

    Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA) nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDI)ZnN(TMS)2-mediated [(BDI) = 2-((2,6-diisopropylphenyl) amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene] ring-opening polymerization of lactide followed by nanoprecipitation. Their lymphatic biodistribution was evaluated by using whole-body fluorescence imaging of nude mice and ex vivo fluorescence imaging of the resected organs. This technique has the potential for providing optical contrast and drug delivery through the lymphatic circulation for the treatment of metastatic cancer. PMID:20487681

  2. Lymphatic Biodistribution of Polylactide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Eric J. Chaney

    2010-05-01

    Full Text Available Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDIZnN(TMS2-mediated [(BDI = 2-((2,6-diisopropylphenyl amido-4-((2,6-diisopropylphenyl-imino-2-pentene] ring-opening polymerization of lactide followed by nanoprecipitation. Their lymphatic biodistribution was evaluated by using whole-body fluorescence imaging of nude mice and ex vivo fluorescence imaging of the resected organs. This technique has the potential for providing optical contrast and drug delivery through the lymphatic circulation for the treatment of metastatic cancer.

  3. New model of macrophage acquisition of the lymphatic endothelial phenotype.

    Directory of Open Access Journals (Sweden)

    Kelly L Hall

    Full Text Available BACKGROUND: Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency in vivo and lack of model systems allowing in-depth molecular analyses in vitro. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions. METHODOLOGY/PRINCIPAL FINDINGS: Time-course analysis of diaphragms from lipopolysaccharide (LPS-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50% incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS in vitro. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b(+/VEGFR-3(+ LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels. CONCLUSIONS/SIGNIFICANCE: We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the "RAW model" mimics

  4. Widespread atypical vascular lesions of the skin after whole-body electron beam therapy: expanding the clinical spectrum.

    Science.gov (United States)

    Sinclair, Werner

    2013-02-01

    Atypical vascular lesion of the skin is an uncommon usually benign condition, thus far reported almost exclusively from mammary skin after radiotherapy for carcinoma of the breast. Some clinical and histological overlap exists with early angiosarcoma, which can also occur on irradiated skin. The lesions are divided into vascular and lymphatic types, the first representing a higher risk for development of angiosarcoma and the latter being more common. This article reports a rare case of widespread, progressive, vascular-type atypical vascular lesion after repeated whole-body electron beam irradiation administered as treatment for mycosis fungoides.

  5. Albendazole for lymphatic filariasis (Review)

    OpenAIRE

    Addiss, D; Gamble, C.; Garner, Paul; Gelband, H; Ejere, H.; Critchley, J.

    2009-01-01

    Background\\ud Mass treatment with albendazole co-administered with another antifilarial drug is part of a global programme to eliminate lymphatic filariasis. We sought reliable evidence of the effects of albendazole on the disease and the parasite.\\ud Objectives\\ud To summarize the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis.\\ud Search strategy\\ud We searched the Cochrane Infectious Diseases Group ...

  6. Lymphatic Regulation of Cellular Trafficking

    Science.gov (United States)

    Jackson, David G.

    2016-01-01

    Lymphatic vessels play vital roles in immune surveillance and immune regulation by conveying antigen loaded dendritic cells, memory T cells, macrophages and neutrophils from the peripheral tissues to draining lymph nodes where they initiate as well as modify immune responses. Until relatively recently however, there was little understanding of how entry and migration through lymphatic vessels is organized or the specific molecular mechanisms that might be involved. Within the last decade, the situation has been transformed by an explosion of knowledge generated largely through the application of microscopic imaging, transgenic animals, specific markers and function blocking mAbs that is beginning to provide a rational conceptual framework. This article provides a critical review of the recent literature, highlighting seminal discoveries that have revealed the fascinating ultrastructure of leucocyte entry sites in lymphatic vessels, as well as generating controversies over the involvement of integrin adhesion, chemotactic and haptotactic mechanisms in DC entry under normal and inflamed conditions. It also discusses the major changes in lymphatic architecture that occur during inflammation and the different modes of leucocyte entry and trafficking within inflamed lymphatic vessels, as well as presenting a timely update on the likely role of hyaluronan and the major lymphatic endothelial hyaluronan receptor LYVE-1 in leucocyte transit.

  7. Immediate and long-term consequences of vascular toxicity during zebrafish development

    Science.gov (United States)

    Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we developed a quantitative ...

  8. Inflammatory manifestations of experimental lymphatic insufficiency.

    Directory of Open Access Journals (Sweden)

    Raymond Tabibiazar

    2006-07-01

    Full Text Available BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

  9. Vascular endothelial growth factor C induces differentiation of bone marrow mesenchymal stem cells into lymphatic endothelial cells%血管内皮生长因子C诱导骨髓间充质干细胞分化为淋巴管内皮细胞的研究

    Institute of Scientific and Technical Information of China (English)

    李波; 刘艳丽; 魏璐婉; 王静; 刘执玉; 丁兆习

    2011-01-01

    Objective To study the differentiation potentiality and inducement conditions of bone marrow mesenchymal stem cells (BMSCs) into lymphatic endothelial cells (LECs), and to provide an ideal source of LECs for lymphatic regeneration and reconstruction. Methods BMSCs were isolated from the bone marrow of SD rats, and the surface antigens CD31, CD14, CD29 and CD90 on BMSCs were detected by flow cytometry. Purified BMSCs were cultured for 10 days in the conditioned medium with vascular endothelial growth factor C (VEGF-C) (50ng/mL). Then, expressions of lymphatic endothelial cell markers, (prospero ho-meobox protein 1 (Prox-1) and lymphatic vessel endothelial receptor 1 (LYVE-1), were detected by Western blot and immunofluorescence. Results BMSCs were typically fusiform in shape and circulate in arrangement, while they transformed into polygonal cells after co-culture with VEGF-C. Flow cytometry showed that expressions of surface antigens CD29 and CD90 on BMSCs were positive, however, CD31and CD14 were negative. After induction with VEGF-C, Western blot and immunofluorescence showed that prox-1 and LYVE-1 were expressed in differentiated BMSCs, while they were not expressed in undifferentiated BMSCs in the control group. Conclusion BMSCs can be induced to express the lymphatic specific antigen and to differentiate into LECs by VEGF-C in vitro.%目的 研究骨髓间充质干细胞向淋巴管内皮细胞分化的潜能及条件,为淋巴管再生和重建提供理想的细胞来源.方法 分离SD大鼠骨髓间充质干细胞,流式细胞仪检测骨髓间充质干细胞表面抗原CD31、CD14、CD29和CD90.将纯化的骨髓间充质干细胞加血管内皮生长因子C(VEGF-C)50 ng/mL诱导培养10 d,Western-blot法与免疫荧光染色法检测细胞中淋巴管内皮细胞标记物Prox-1和LYVE-1的表达.结果 骨髓间充质干细胞呈现典型的梭形和旋涡状排列;经VEGF-C诱导后,细胞变短、呈多边形.流式细胞学显示,分离培养的骨

  10. Lymphatic vessel density and function in experimental bladder cancer

    Directory of Open Access Journals (Sweden)

    Maier Julie

    2007-11-01

    Full Text Available Abstract Background The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. Methods A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ, we examined the lymphatic vessel density (LVD and function (LVF during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5 suitable for both magnetic resonance imaging (MRI and near infrared fluorescence (NIRF. In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. Results SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic

  11. Development of lymphatic filarial parasite Wuchereria bancrofti (Spirurida: Onchocercidae) in mosquito species (Diptera: Culicidae) fed artificially on microfilaremic blood.

    Science.gov (United States)

    Paily, K P; Hoti, S L; Balaraman, K

    2006-11-01

    The efficiency of laboratory colonies of mosquitoes such as Anopheles stephensi Liston, Aedes aegypti (L.) Liverpool strain, Ae. aegypti wild type, Aedes albopictus (Skuse), Culex tritaeniorhynchus Giles, Culex sitiens Wiedemann, and Armigeres subalbatus Coquillett in supporting the development of Wuchereria bancrofti (Cobbold) (Spirurida: Onchocercidae) microfilariae to infective larvae was investigated. The mosquitoes were fed on heparinized microfilaremic human blood by using a membrane-feeding unit with Parafilm as membrane. The rate of infection, parasite development, and parasite burden were compared with that in the known vector mosquito Culex quinquefasciatus Say. Cx. quinquefasciatus showed the highest percentage of infection, followed by Ae. aegypti Liverpool strain and An. stephensi. The rate of development of the parasite was more or less similar in all the three species, and infective larvae were found on day 13. When the larvae were harvested on day 17, Cx. quinquefasciatus yielded the highest numbers, followed by Ae. aegypti Liverpool strain and An. stephensi. The percentage of infection was low, and the development was slow in Cx. tritaeniorhynchus compared with the other susceptible species. The parasite developed to second-stage larvae only by day 22 and to infective larvae by day 28. When 2-wk-old Cx. tritaeniorhynchus were fed on microfilaremic blood, they could develop the parasite to infective larvae by day 13 postfeeding. All other species of mosquitoes tested were found to be refractory to parasite development. It is shown that Cx. quinquefasciatus is the most suitable mosquito host for the production of infective larvae. However, Ae. aegypti Liverpool strain, which is commonly used for Brugia malayi filarial parasite, also can be used for generation of W. bancrofti infective larvae to circumvent the problem of maintaining two mosquito species.

  12. Cardiac mouse lymphatics: developmental and anatomical update.

    Science.gov (United States)

    Flaht-Zabost, Aleksandra; Gula, Grzegorz; Ciszek, Bogdan; Czarnowska, Elżbieta; Jankowska-Steifer, Ewa; Madej, Maria; Niderla-Bielińska, Justyna; Radomska-Leśniewska, Dorota; Ratajska, Anna

    2014-06-01

    The adult mouse heart possesses an extensive lymphatic plexus draining predominantly the subepicardium and the outer layer of the myocardial wall. However, the development of this plexus has not been entirely explored, partially because of the lack of suitable methods for its visualization as well as prolonged lymphatic vessel formation that starts prenatally and proceeds during postnatal stages. Also, neither the course nor location of collecting vessels draining lymph from the mouse heart have been precisely characterized. In this article, we report that murine cardiac lymphatic plexus development that is limited prenatally only to the subepicardial area, postnatally proceeds from the subepicardium toward the myocardial wall with the base-to-apex gradient; this plexus eventually reaches the outer half of the myocardium with a predominant location around branches of coronary arteries and veins. Based on multiple marker immunostaining, the molecular marker-phenotype of cardiac lymphatic endothelial cells can be characterized as: Prox-1(+), Lyve-1(+), VEGFR3(+), Podoplanin(+), VEGFR2(+), CD144(+), Tie2(+), CD31(+), vWF(-), CD34(-), CD133(-). There are two major collecting vessels: one draining the right and left ventricles along the left conal vein and running upwards to the left side of the pulmonary trunk and further to the nearest lymph nodes (under the aortic arch and near the trachea), and the other one with its major branch running along the left cardiac vein and further on the surface of the coronary sinus and the left atrium to paratracheal lymph nodes. The extracardiac collectors gain the smooth muscle cell layer during late postnatal stages.

  13. The surgical anatomy of the lymphatic system of the pancreas.

    Science.gov (United States)

    Cesmebasi, Alper; Malefant, Jason; Patel, Swetal D; Du Plessis, Maira; Renna, Sarah; Tubbs, R Shane; Loukas, Marios

    2015-05-01

    The lymphatic system of the pancreas is a complex, intricate network of lymphatic vessels and nodes responsible for the drainage of the head, neck, body, and tail of the pancreas. Its anatomical divisions and embryological development have been well described in the literature with emphasis on its clinical relevance in regards to pancreatic pathologies. A thorough knowledge and understanding of the lymphatic system surrounding the pancreas is critical for physicians in providing diagnostic and treatment strategies for patients with pancreatic cancer and pancreatitis. Pancreatic cancer has an extremely poor prognosis and is a notable cause of morbidity and mortality worldwide. Although a surgeon may try to predict the routes for metastasis for pancreatic cancer, the complexity of this system presents difficulty due to variable drainage patterns. Pancreatitis also presents as another severe disease which has been shown to have an association with the lymphatics. The aim of this article is to review the literature on the lymphatics of the pancreas, pancreatic pathologies, and the available imaging methodologies used to study the pancreatic lymphatics.

  14. Photoacoustic lymphatic imaging with high spatial-temporal resolution

    Science.gov (United States)

    Martel, Catherine; Yao, Junjie; Huang, Chih-Hsien; Zou, Jun; Randolph, Gwendalyn J.; Wang, Lihong V.

    2014-11-01

    Despite its critical function in coordinating the egress of inflammatory and immune cells out of tissues and maintaining fluid balance, the causative role of lymphatic network dysfunction in pathological settings is still understudied. Engineered-animal models and better noninvasive high spatial-temporal resolution imaging techniques in both preclinical and clinical studies will help to improve our understanding of different lymphatic-related pathologic disorders. Our aim was to take advantage of our newly optimized noninvasive wide-field fast-scanning photoacoustic (PA) microcopy system to coordinately image the lymphatic vasculature and its flow dynamics, while maintaining high resolution and detection sensitivity. Here, by combining the optical-resolution PA microscopy with a fast-scanning water-immersible microelectromechanical system scanning mirror, we have imaged the lymph dynamics over a large field-of-view, with high spatial resolution and advanced detection sensitivity. Depending on the application, lymphatic vessels (LV) were spectrally or temporally differentiated from blood vessels. Validation experiments were performed on phantoms and in vivo to identify the LV. Lymphatic flow dynamics in nonpathological and pathological conditions were also visualized. These results indicate that our newly developed PA microscopy is a promising tool for lymphatic-related biological research.

  15. Vascular development and hemodynamic force in the mouse yolk sac

    Directory of Open Access Journals (Sweden)

    Monica D Garcia

    2014-08-01

    Full Text Available Vascular remodeling of the mouse embryonic yolk sac is a highly dynamic process dependent on multiple genetic signaling pathways as well as biomechanical factors regulating proliferation, differentiation, migration, cell-cell and cell-matrix interactions. During this early developmental window, the initial primitive vascular network of the yolk sac undergoes a dynamic remodeling process concurrent with the onset of blood flow, in which endothelial cells establish a branched, hierarchical structure of large vessels and smaller capillary beds. In this review, we will describe the molecular and biomechanical regulators which guide vascular remodeling in the mouse embryonic yolk sac, as well as live imaging methods for characterizing endothelial cell and hemodynamic function in cultured embryos.

  16. Altered lymphatic function and architecture in salt-induced hypertension assessed by near-infrared fluorescence imaging

    Science.gov (United States)

    Kwon, Sunkuk; Agollah, Germaine D.; Chan, Wenyaw; Sevick-Muraca, Eva M.

    2012-08-01

    The lymphatic system plays an important role in maintaining the fluid homeostasis between the blood vascular and interstitial tissue compartment and there is recent evidence that its transport capabilities may regulate blood pressure in salt-induced hypertension. Yet, there is little known how the lymphatic contractile function and architecture responds to dietary salt-intake. Thus, we longitudinally characterized lymphatic contractile function and vessel remodeling noninvasively using dynamic near-infrared fluorescence imaging in animal models of salt-induced hypertension. The lymphatics of mice and rats were imaged following intradermal injection of indocyanine green to the ear tip or the base of the tail before and during two weeks of either a high salt diet (HSD) or normal chow. Our noninvasive imaging data demonstrated dilated lymphatic vessels in the skin of mice and rats on a HSD as compared to their baseline levels. In addition, our dynamic imaging results showed increased lymphatic contraction frequency in HSD-fed mice and rats. Lymphatic contractile function and vessel remodeling occurs in response to salt-induced hypertension suggesting a possible role for the lymphatics in the regulation of vascular blood pressure.

  17. Mechanisms of lymphatic regeneration after tissue transfer.

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    Alan Yan

    Full Text Available INTRODUCTION: Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer. METHODS: Nude mice (recipients underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed. RESULTS: Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration. CONCLUSIONS: Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics

  18. Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema.

    Science.gov (United States)

    Honkonen, Krista M; Visuri, Mikko T; Tervala, Tomi V; Halonen, Paavo J; Koivisto, Mari; Lähteenvuo, Markku T; Alitalo, Kari K; Ylä-Herttuala, Seppo; Saaristo, Anne M

    2013-05-01

    Our objective was to define the optimal growth factor treatment to be used in combination with lymph node transfer to normalize lymphatic vascular anatomy. In the lymph node transfer method, lymphatic anastomoses are expected to form spontaneously. However, lymphangiogenic growth factor therapies have shown promising results in preclinical models of lymphedema. The inguinal lymphatic vasculature of pigs was surgically destroyed around the inguinal lymph node. To enhance the regrowth of the lymphatic network in the defected area, adenoviral vascular endothelial growth factor C (VEGF-C) was administered intranodally or perinodally. Control animals received injections of saline or control vector. The lymphangiogenic effect of the growth factor therapy and any potential adverse effects associated with the 2 alternative delivery routes were examined 2 months postoperatively. Both routes of growth factor administration induced robust growth of lymphatic vessels and helped to preserve the structure of the transferred lymph nodes in comparison with the controls. The lymph nodes of the control treated animals regressed in size and their nodal structure was partly replaced by fibro-fatty scar tissue. Intranodally injected adenoviral VEGF-C and adenoviral vector encoding control gene LacZ induced macrophage accumulation inside the node, whereas perinodal administration of VEGF-C did not have this adverse effect. Lymphangiogenic growth factors improve lymphatic vessel regeneration and lymph node function after lymph node transfer. The perinodal route of delivery provides a basis for future clinical trials in lymphedema patients.

  19. Development of Embedded Vascular Networks in FRP for Active/Passive Thermal Management

    Science.gov (United States)

    2015-04-01

    AFRL-AFOSR-UK-TR-2015-0019 Development of Embedded Vascular Networks in FRP for Active/Passive Thermal Management Katarzyna...To) 30 September 2012 – 31 December 2014 4. TITLE AND SUBTITLE Development of Embedded Vascular Networks in FRP for Active/Passive Thermal...Z39-18     Page 1 of 16     Project  Title:      Development  of   Embedded  Vascular  Networks  in  FRP  for

  20. Analysis of vascular development in the hydra sterol biosynthetic mutants of Arabidopsis.

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    Margaret Pullen

    Full Text Available The control of vascular tissue development in plants is influenced by diverse hormonal signals, but their interactions during this process are not well understood. Wild-type sterol profiles are essential for growth, tissue patterning and signalling processes in plant development, and are required for regulated vascular patterning.Here we investigate the roles of sterols in vascular tissue development, through an analysis of the Arabidopsis mutants hydra1 and fackel/hydra2, which are defective in the enzymes sterol isomerase and sterol C-14 reductase respectively. We show that defective vascular patterning in the shoot is associated with ectopic cell divisions. Expression of the auxin-regulated AtHB8 homeobox gene is disrupted in mutant embryos and seedlings, associated with variably incomplete vascular strand formation and duplication of the longitudinal axis. Misexpression of the auxin reporter proIAA2ratioGUS and mislocalization of PIN proteins occurs in the mutants. Introduction of the ethylene-insensitive ein2 mutation partially rescues defective cell division, localization of PIN proteins, and vascular strand development.The results support a model in which sterols are required for correct auxin and ethylene crosstalk to regulate PIN localization, auxin distribution and AtHB8 expression, necessary for correct vascular development.

  1. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.

    2010-01-01

    In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs...

  2. Lymphatic filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Kisinza, William N.

    2013-01-01

    Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA...

  3. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.;

    2010-01-01

    In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with t...

  4. Bioresorbable vascular scaffolds technology: current use and future developments

    Directory of Open Access Journals (Sweden)

    Giacchi G

    2016-07-01

    Full Text Available Giuseppe Giacchi, Luis Ortega-Paz, Salvatore Brugaletta, Kohki Ishida, Manel Sabaté Cardiology Department, Clinic Cardiovascular Institute, Hospital Clinic, August Pi and Sunyer Biomedical Research Institute (IDIBAPS, University of Barcelona, Barcelona, Spain Abstract: Coronary bioresorbable vascular scaffolds are a new appealing therapeutic option in interventional cardiology. The most used and studied is currently the Absorb BVS™. Its backbone is made of poly-l-lactide and coated by a thin layer of poly-d,l-lactide, it releases everolimus and is fully degraded to H2O and CO2 in 2–3 years. Absorb BVS™ seems to offer several theoretical advantages over metallic stent, as it gives temporary mechanical support to vessel wall without permanently caging it. Therefore, long-term endothelial function and structure are not affected. A possible future surgical revascularization is not compromised. Natural vasomotion in response to external stimuli is also recovered. Several observational and randomized trials have been published about BVS clinical outcomes. The main aim of this review is to carry out a systematic analysis about Absorb BVS™ studies, evaluating also the technical improvements of the Absorb GT1 BVS™. Keywords: Absorb GT1, Absorb BVS™, bioresorbable vascular scaffold, BRS, coronary scaffold

  5. Is tuberculosis a lymphatic disease with a pulmonary portal?

    Science.gov (United States)

    Behr, Marcel A; Waters, W Ray

    2014-03-01

    Tuberculosis most commonly presents as a pulmonary disease, in which infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a pulmonary disease, enlarged lymph nodes represent reactive adenitis, and extrapulmonary forms of tuberculosis (including lymphatic tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human tuberculosis from the preantibiotic era, analogy with other mycobacterial infections, observations of tuberculosis in non-human hosts, and experimental models of tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes tuberculosis as a lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and vaccines.

  6. [Anatomy of the pelvic lymphatic system].

    Science.gov (United States)

    Wolfram-Gabel, R

    2013-10-01

    The lymphatic system of the pelvis collects the lymph of the genital and urinary organs and of the digestive tract. It is formed by lymphatic nodes and vessels situated inside the conjunctive tissue, near the organs (visceral lymphatic nodes) but especially along the external, internal and common iliac vessels (iliac lymphatic nodes). These nodes receive afferent vessels issued from the different pelvic organs. From the iliac lymphnodes arise efferent vessels running towards lymphatic collectors, situated above them, and which end in the lymphatic lombar duct. The lymphatic pathways represent the preferential way of scattering of cancerous cells. Therefore, the knowledge of the anatomy, of the situation and of the draining of the nodes is of the utmost importance in the evaluation of a cancer of a pelvic organ.

  7. Digging deeper into lymphatic vessel formation in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Thiry Marc

    2011-06-01

    Full Text Available Abstract Background Abnormal lymphatic vessel formation (lymphangiogenesis is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays distinctive features than blood vasculature, and mechanisms underlying the formation of new lymphatic vessels during physiological and pathological processes are still poorly documented. Most studies on lymphatic vessel formation are focused on organism development rather than lymphangiogenic events occurring in adults. We have here studied lymphatic vessel formation in two in vivo models of pathological lymphangiogenesis (corneal assay and lymphangioma. These data have been confronted to those generated in the recently set up in vitro model of lymphatic ring assay. Ultrastructural analyses through Transmission Electron Microscopy (TEM were performed to investigate tube morphogenesis, an important differentiating process observed during endothelial cell organization into capillary structures. Results In both in vivo models (lymphangiogenic corneal assay and lymphangioma, migrating lymphatic endothelial cells extended long processes exploring the neighboring environment and organized into cord-like structures. Signs of intense extracellular matrix remodeling were observed extracellularly and inside cytoplasmic vacuoles. The formation of intercellular spaces between endothelial cells led to tube formation. Proliferating lymphatic endothelial cells were detected both at the tips of sprouting capillaries and inside extending sprouts. The different steps of lymphangiogenesis observed in vivo are fully recapitulated in vitro, in the lymphatic ring assay and include: (1 endothelial cell alignment in cord like structure, (2 intracellular vacuole formation and (3 matrix degradation. Conclusions In this study, we are providing evidence for lymphatic vessel formation through tunneling relying on extensive matrix remodeling, migration and alignment of

  8. Imaging evaluation of fetal vascular anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal [MLC 5031 Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Adams, Denise M. [Cincinnati Children' s Hospital Medical Center, Department of Pediatrics and Hemangioma and Vascular Malformation Center, Cincinnati, OH (United States); Gupta, Anita [Cincinnati Children' s Hospital Medical Center, Department of Pathology, Cincinnati, OH (United States); Lim, Foong-Yen [Cincinnati Children' s Hospital Medical Center, Pediatric Surgery and Fetal Center of Cincinnati, Cincinnati, OH (United States)

    2015-08-15

    Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification. (orig.)

  9. Modelling the development and arrangement of the primary vascular structure in plants.

    Science.gov (United States)

    Cartenì, Fabrizio; Giannino, Francesco; Schweingruber, Fritz Hans; Mazzoleni, Stefano

    2014-09-01

    The process of vascular development in plants results in the formation of a specific array of bundles that run throughout the plant in a characteristic spatial arrangement. Although much is known about the genes involved in the specification of procambium, phloem and xylem, the dynamic processes and interactions that define the development of the radial arrangement of such tissues remain elusive. This study presents a spatially explicit reaction-diffusion model defining a set of logical and functional rules to simulate the differentiation of procambium, phloem and xylem and their spatial patterns, starting from a homogeneous group of undifferentiated cells. Simulation results showed that the model is capable of reproducing most vascular patterns observed in plants, from primitive and simple structures made up of a single strand of vascular bundles (protostele), to more complex and evolved structures, with separated vascular bundles arranged in an ordered pattern within the plant section (e.g. eustele). The results presented demonstrate, as a proof of concept, that a common genetic-molecular machinery can be the basis of different spatial patterns of plant vascular development. Moreover, the model has the potential to become a useful tool to test different hypotheses of genetic and molecular interactions involved in the specification of vascular tissues.

  10. Vascular endothelial growth factor co-ordinates proper development of lung epithelium and vasculature.

    Science.gov (United States)

    Zhao, Liqing; Wang, Ke; Ferrara, Napoleone; Vu, Thiennu H

    2005-07-01

    The vasculature forms an intrinsic functional component of the lung and its development must be tightly regulated and coordinated with lung epithelial morphogenesis. Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in a complementary pattern in the lungs during embryonic development. VEGF is expressed by epithelium and the receptors in the surrounding mesenchyme. To determine the function of VEGF in lung formation, we inhibited its activity using a soluble receptor in lung renal capsule grafts. Inhibition of VEGF results in inhibition of vascular development and significant alteration in epithelial development. Epithelial proliferation is inhibited, sacculation is impaired, and the epithelium undergoes apoptosis. Interestingly, when VEGF is attenuated, epithelial differentiation still proceeds, as shown by acquisition of both proximal and distal markers. These data show that VEGF co-ordinates epithelial and vascular development. It is required for the development of the lung vasculature and the vasculature is necessary for epithelial proliferation and morphogenesis, but not for cell differentiation.

  11. Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis

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    Francesca Luisi

    2016-06-01

    Full Text Available Generalised lymphatic anomaly (GLA, also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from single-organ involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches.

  12. Vascular endothelial growth factor signaling regulates the segregation of artery and vein via ERK activity during vascular development

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Se-Hee [McAllister Heart Institute, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); Schmitt, Christopher E.; Woolls, Melissa J. [McAllister Heart Institute, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Dept. of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511 (United States); Holland, Melinda B. [McAllister Heart Institute, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States); Kim, Jun-Dae [Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Dept. of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511 (United States); Jin, Suk-Won, E-mail: suk-won.jin@yale.edu [Yale Cardiovascular Research Center and Section of Cardiovascular Medicine, Dept. of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511 (United States)

    2013-01-25

    Highlights: ► VEGF-A signaling regulates the segregation of axial vessels. ► VEGF-A signaling is mediated by PKC and ERK in this process. ► Ectopic activation of ERK is sufficient to rescue defects in vessel segregation. -- Abstract: Segregation of two axial vessels, the dorsal aorta and caudal vein, is one of the earliest patterning events occur during development of vasculature. Despite the importance of this process and recent advances in our understanding on vascular patterning during development, molecular mechanisms that coordinate the segregation of axial vessels remain largely elusive. In this report, we find that vascular endothelial growth factor-A (Vegf-A) signaling regulates the segregation of dorsal aorta and axial vein during development. Inhibition of Vegf-A pathway components including ligand Vegf-A and its cognate receptor Kdrl, caused failure in segregation of axial vessels in zebrafish embryos. Similarly, chemical inhibition of Mitogen-activated protein kinase kinase (Map2k1)/Extracellular-signal-regulated kinases (Erk) and phosphatidylinositol 3-kinases (PI3 K), which are downstream effectors of Vegf-A signaling pathway, led to the fusion of two axial vessels. Moreover, we find that restoring Erk activity by over-expression of constitutively active MEK in embryos with a reduced level of Vegf-A signaling can rescue the defects in axial vessel segregation. Taken together, our data show that segregation of axial vessels requires the function of Vegf-A signaling, and Erk may function as the major downstream effector in this process.

  13. ETS Transcription Factor ETV2/ER71/Etsrp in Hematopoietic and Vascular Development.

    Science.gov (United States)

    Sumanas, S; Choi, K

    2016-01-01

    Effective establishment of the hematopoietic and vascular systems is prerequisite for successful embryogenesis. The ETS transcription factor Etv2 has proven to be essential for hematopoietic and vascular development. Etv2 expression marks the onset of the hematopoietic and vascular development and its deficiency leads to an absolute block in hematopoietic and vascular development. Etv2 is transiently expressed during development and is mainly expressed in testis in adults. Consistent with its expression pattern, Etv2 is transiently required for the generation of the optimal levels of the hemangiogenic cell population. Deletion of this gene after the hemangiogenic progenitor formation leads to normal hematopoietic and vascular development. Mechanistically, ETV2 induces the hemangiogenic program by activating blood and endothelial cell lineage specifying genes and enhancing VEGF signaling. Moreover, ETV2 establishes an ETS hierarchy by directly activating other Ets genes, which in the face of transient Etv2 expression, presumably maintain blood and endothelial cell program initiated by ETV2 through an ETS switching mechanism. Current studies suggest that the hemangiogenic progenitor population is exclusively sensitive to ETV2-dependent FLK1 signaling. Any perturbation in the ETV2, VEGF, and FLK1 balance causing insufficient hemangiogenic progenitor cell generation would lead to defects in hematopoietic and endothelial cell development.

  14. Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Guo; Ling Chen; Ronggang Lang; Yu Fan; Li Fu

    2006-01-01

    OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast.METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases.RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma.CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.

  15. Lymphatic territories (lymphosomes in a canine: an animal model for investigation of postoperative lymphatic alterations.

    Directory of Open Access Journals (Sweden)

    Hiroo Suami

    Full Text Available BACKGROUND: Lymph node dissection is often performed as a part of surgical treatment for breast cancer and malignant melanoma to prevent malignant cells from traveling via the lymphatic system. Currently little is known about postoperative lymphatic drainage pattern alterations. This knowledge may be useful for management of recurrent cancer and prevention of breast cancer related lymphedema. We mapped the complete superficial lymphatic system of a dog and used this canine model to perform preliminary studies of lymphatic architectural changes in postoperative condition. METHODS: Lymphatic territories (lymphosomes were mapped with 4 female mongrel carcasses using an indocyanine green (ICG fluorescent lymphography and a radiographic microinjection technique. Two live dogs were then subjected to unilateral lymph node dissection of lymph basins of the forelimb, and ICG lymphography and lymphangiogram were performed 6 months after the surgery to investigate lymphatic changes. Lymphatic patterns in the carcass were then compared with postoperative lymphatic patterns in the live dogs. RESULTS: Ten lymphosomes were identified, corresponding with ten lymphatic basins. Postoperative fluorescent lymphographic images and lymphangiograms in the live dogs revealed small caliber lymphatic network fulfilling gaps in the surgical area and collateral lymphatic vessels arising from the network connecting to lymph nodes in the contralateral and ipsilateral neck in one dog and the ipsilateral subclavicular vein in another dog. CONCLUSION: Our canine lymphosome map allowed us to observe lymphatic collateral formations after lymph node dissection in live dogs. This canine model may help clarify our understanding of postoperative lymphatic changes in humans in future studies.

  16. Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors

    Energy Technology Data Exchange (ETDEWEB)

    Ran, Sophia, E-mail: sran@siumed.edu; Montgomery, Kyle E. [Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N. Rutledge, Springfield, IL 62794 (United States)

    2012-06-27

    It is widely accepted that macrophages and other inflammatory cells support tumor progression and metastasis. During early stages of neoplastic development, tumor-infiltrating macrophages (TAMs) mount an immune response against transformed cells. Frequently, however, cancer cells escape the immune surveillance, an event that is accompanied by macrophage transition from an anti-tumor to a pro-tumorigenic type. The latter is characterized by high expression of factors that activate endothelial cells, suppress immune response, degrade extracellular matrix, and promote tumor growth. Cumulatively, these products of TAMs promote tumor expansion and growth of both blood and lymphatic vessels that facilitate metastatic spread. Breast cancers and other epithelial malignancies induce the formation of new lymphatic vessels (i.e., lymphangiogenesis) that leads to lymphatic and subsequently, to distant metastasis. Both experimental and clinical studies have shown that TAMs significantly promote tumor lymphangiogenesis through paracrine and cell autonomous modes. The paracrine effect consists of the expression of a variety of pro-lymphangiogenic factors that activate the preexisting lymphatic vessels. The evidence for cell-autonomous contribution is based on the observed tumor mobilization of macrophage-derived lymphatic endothelial cell progenitors (M-LECP) that integrate into lymphatic vessels prior to sprouting. This review will summarize the current knowledge of macrophage-dependent growth of new lymphatic vessels with specific emphasis on an emerging role of macrophages as lymphatic endothelial cell progenitors (M-LECP)

  17. Albendazole for lymphatic filariasis (Review)

    OpenAIRE

    Addiss, D; Critchley, J.; Ejere, H.; Garner, Paul; Gelband, H; Gamble, C.

    2005-01-01

    Background\\ud Mass treatment with albendazole, co-administered with another antifilarial drug, is being promoted as part of a global programme to eliminate lymphatic filariasis.\\ud Objectives\\ud To assess the effects of albendazole on patients or populations with filarial infection, and on morbidity in patients with filarial infection; and to assess the frequency of adverse events for albendazole both given singly or in combination with another antifilarial drug (diethylcarbamazine or ivermec...

  18. Orofacial lymphatic malformation: management with a three steps diode laser protocol

    Science.gov (United States)

    Miccoli, Simona; Tempesta, Angela; Limongelli, Luisa; Caporusso, Concetta; Di Venere, Daniela; Petruzzi, Massimo; Lacaita, Mariagrazia; Maiorano, Eugenio; Favia, Gianfranco

    2014-01-01

    Lymphatic Malformation (LM) according to ISSVA Classification, is a rare benign disorder with unknown aetiology. LM may grow slowly over years or develop rapidly over the course of days becoming a bulky lump, infected or bleeding. We propose our three steps Diode Laser protocol for LM management, based on its persistent vascular blood component. 1. Histological and cytological examination, to evaluate the vascular blood component (10-40%), shows mature lymphocytes with red blood cells and endothelial cells. 2. Diode Laser Photocoagulation (DLP) in pulsed mode (on 100ms / off 400ms) at 10W and 800nm with a 300μm fibre kept 2-3mm from the tissues, to reduce the lesion. 3. Diode Laser surgical excision in pulsed mode (on 50ms / off 200ms) at 8W and 800nm with a 300 μm fibre in close contact with tissues, and histological intraoperative margins control on frozen sections. Even if it has inconstant results (lesions decreasing rate is 10% to 40% proportionally to vascular blood component), DLP simplifies the last and the most important step. Use of Diode Laser also in surgical excision reduces intra and postoperatory complications.

  19. Fluorescein sodium fluorescence microscope-integrated lymphangiography for lymphatic supermicrosurgery.

    Science.gov (United States)

    Ayestaray, Benoit; Bekara, Farid

    2015-07-01

    Microscope-integrated lymphangiography is a useful method in the field of lymphatic supermicrosurgery. Fluorescence based on indocyanine green (ICG) is the most commonly used. Fluorescein sodium is a fluorescent tracer used for retinal and neurosurgical angiography but not yet for lymphatic supermicrosurgery. In this report, we present a case in which the fluorescein sodium fluorescence microscope-integrated lymphangiography was used for assessment of lymphatic drainage pathway and patency in a patient treated for secondary lymphedema by lymphaticovenular anastomoses. Fluorescein sodium fluorescence microscope-integrated lymphangiography was evaluated in a 67-year-old female presented for a Campisi clinical stage IV lymphedema of the upper limb. Transcutaneous guidance and vascular fluorescence were assessed. A comparison with ICG fluorescence was made intraoperatively. Two lymphaticovenular anastomoses were performed and their patency were checked by lymphangiography. Transcutaneous signal was found higher with fluorescein sodium fluorescence. Intraluminal visualization was possible with fluorescein sodium coloration during lymphaticovenular anastomoses. No adverse reaction occurred. The circumferential differential reduction rate of affected limb was 8.1% 3 months after lymphaticovenular anastomoses. The use of fluorescence microscope-integrated lymphangiography with fluorescein sodium may be superior to ICG fluorescence in assistance of lymphaticovenular anastomoses. © 2015 Wiley Periodicals, Inc.

  20. Migration and lymphatic spread of calcified paraffinomas after breast augmentation

    Energy Technology Data Exchange (ETDEWEB)

    Ooi, G.C.; Peh, W.C.G.; Ip, M. [Hong Kong Univ. (Hong Kong)

    1996-11-01

    A 62 year old Chinese woman presented 25 years after having both breasts augmented with paraffin injections. Development of paraffinomas and multiple episodes of paraffin-related mastitis eventually resulted in bilateral mastectomies. The unusual distribution of migrated calcified paraffinomas in the thoracic wall and its lymphatic system is documented on computed tomography. 12 refs., 2 figs.

  1. Sox7, Sox17, and Sox18 Cooperatively Regulate Vascular Development in the Mouse Retina.

    Directory of Open Access Journals (Sweden)

    Yulian Zhou

    Full Text Available Vascular development and maintenance are controlled by a complex transcriptional program, which integrates both extracellular and intracellular signals in endothelial cells. Here we study the roles of three closely related SoxF family transcription factors-Sox7, Sox17, and Sox18 -in the developing and mature mouse vasculature using targeted gene deletion on a mixed C57/129/CD1 genetic background. In the retinal vasculature, each SoxF gene exhibits a distinctive pattern of expression in different classes of blood vessels. On a mixed genetic background, vascular endothelial-specific deletion of individual SoxF genes has little or no effect on vascular architecture or differentiation, a result that can be explained by overlapping function and by reciprocal regulation of gene expression between Sox7 and Sox17. By contrast, combined deletion of Sox7, Sox17, and Sox18 at the onset of retinal angiogenesis leads to a dense capillary plexus with a nearly complete loss of radial arteries and veins, whereas the presence of a single Sox17 allele largely restores arterial identity, as determined by vascular smooth muscle cell coverage. In the developing retina, expression of all three SoxF genes is reduced in the absence of Norrin/Frizzled4-mediated canonical Wnt signaling, but SoxF gene expression is unaffected by reduced VEGF signaling in response to deletion of Neuropilin1 (Npn1. In adulthood, Sox7, Sox17, and Sox18 act in a largely redundant manner to maintain blood vessel function, as adult onset vascular endothelial-specific deletion of all three SoxF genes leads to massive edema despite nearly normal vascular architecture. These data reveal critical and partially redundant roles for Sox7, Sox17 and Sox18 in vascular growth, differentiation, and maintenance.

  2. Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development.

    Science.gov (United States)

    Magnusson, Peetra; Rolny, Charlotte; Jakobsson, Lars; Wikner, Charlotte; Wu, Yan; Hicklin, Daniel J; Claesson-Welsh, Lena

    2004-03-15

    We have employed embryoid bodies derived from murine embryonal stem cells to study effects on vascular development induced by fibroblast growth factor (FGF)-2 and FGF receptor-1, in comparison to the established angiogenic factor vascular endothelial growth factor (VEGF)-A and its receptor VEGF receptor-2. Exogenous FGF-2 promoted formation of morphologically distinct, long slender vessels in the embryoid bodies, whereas VEGF-A-treated bodies displayed a compact plexus of capillaries. FGF-2 stimulation of embryonal stem cells under conditions where VEGF-A/VEGFR-2 function was blocked, led to formation of endothelial cell clusters, which failed to develop into vessels. FGFR-1(-/-) embryoid bodies responded to VEGF-A by establishment of the characteristic vascular plexus, but FGF-2 had no effect on vascular development in the absence of FGFR-1. The FGFR-1(-/-) embryoid bodies displayed considerably increased basal level of vessel formation, detected by immunohistochemical staining for platelet-endothelial cell adhesion molecule (PECAM)/CD31. This basal vascularization was blocked by neutralizing antibodies against VEGFR-2 or VEGF-A and biochemical analyses indicated changes in regulation of VEGFR-2 in the absence of FGFR-1 expression. We conclude that VEGF-A/VEGFR-2-dependent vessel formation occurs in the absence of FGF-2/FGFR-1, which, however, serve to modulate vascular development.

  3. Lymphatics and Lymphangiogenesis in the Eye

    Directory of Open Access Journals (Sweden)

    Shintaro Nakao

    2012-01-01

    Full Text Available Lymphatic is a prerequisite for the maintenance of tissue fluid balance and immunity in the body. A body of evidence also shows that lymphangiogenesis plays important roles in the pathogenesis of diseases such as tumor metastasis and inflammation. The eye was thought to lack lymphatic vessels except for the conjunctiva; however, advances in the field, including the identification of lymphatic endothelial markers (e.g., LYVE-1 or podoplanin and lymphangiogenic factors (e.g., VEGF-C, have revealed the exsitence and possible roles of lymphatics and lymphangiogenesis in the eye. Recent studies have shown that corneal limbus, ciliary body, lacrimal gland, orbital meninges, and extraocular muscles contain lymphatic vessels and that the choroid might have a lymphatic-like system. There is no known lymphatic outflow from the eye. However, several lymphatic channels including uveolymphatic pathway might serve the ocular fluid homeostasis. Furthermore, lymphangiogenesis plays important roles in pathological conditions in the eye including corneal transplant rejection and ocular tumor progression. Yet, the role of lymphangiogenesis in most eye diseases, especially inflammatory disease or edema, remains unknown. A better understanding of lymphatic and lymphangiogenesis in the eye will open new therapeutic opportunities to prevent vision loss in ocular diseases.

  4. Lymphatics and cancer : VEGF-C and nitric oxide in lymphatic function, lymphangiogenesis, and metastasis

    NARCIS (Netherlands)

    Hagendoorn, Jeroen

    2006-01-01

    The lymphatics are a primary route for cancer metastasis and lymph node metastasis is an important clinical prognostic factor. The process of lymphatic metastasis is, however, not well understood. This thesis examines the function of lymphatic vessels in relation to cancer progression and metastasis

  5. History and conceptual developments in vascular biology and angiogenesis research: a personal view.

    Science.gov (United States)

    Bikfalvi, Andreas

    2017-07-24

    Vascular biology is an important scientific domain that has gradually penetrated many medical and scientific fields. Scientists are most often focused on present problems in their daily scientific work and lack awareness regarding the evolution of their domain throughout history and of how philosophical issues are related to their research field. In this article, I provide a personal view with an attempt to conceptualize vascular development research that articulates lessons taken from history, philosophy, biology and medicine. I discuss selected aspects related to the history and the philosophy of sciences that can be extracted from the study of vascular development and how conceptual progress in this research field has been made. I will analyze paradigm shifts, cross-fertilization of different fields, technological advances and its impact on angiogenesis and discuss issues related to evolutionary biology, proximity of different molecular systems and scientific methodologies. Finally, I discuss briefly my views where the field is heading in the future.

  6. Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the developing retinal vasculature.

    Directory of Open Access Journals (Sweden)

    Andrew Scott

    Full Text Available Vascular endothelial growth factor (VEGF plays a critical role in normal development as well as retinal vasculature disease. During retinal vascularization, VEGF is most strongly expressed by not yet vascularized retinal astrocytes, but also by retinal astrocytes within the developing vascular plexus, suggesting a role for retinal astrocyte-derived VEGF in angiogenesis and vessel network maturation. To test the role of astrocyte-derived VEGF, we used Cre-lox technology in mice to delete VEGF in retinal astrocytes during development. Surprisingly, this only had a minor impact on retinal vasculature development, with only small decreases in plexus spreading, endothelial cell proliferation and survival observed. In contrast, astrocyte VEGF deletion had more pronounced effects on hyperoxia-induced vaso-obliteration and led to the regression of smooth muscle cell-coated radial arteries and veins, which are usually resistant to the vessel-collapsing effects of hyperoxia. These results suggest that VEGF production from retinal astrocytes is relatively dispensable during development, but performs vessel stabilizing functions in the retinal vasculature and might be relevant for retinopathy of prematurity in humans.

  7. Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway.

    Science.gov (United States)

    Yu, Shengjin; Lv, Huiming; Zhang, He; Jiang, Yu; Hong, Yu; Xia, Rongjun; Zhang, Qifang; Ju, Weiwei; Jiang, Lili; Ou, Geng; Zhang, Jinhui; Wang, Shujing; Zhang, Jianing

    2017-02-13

    Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface. Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell. Further studies indicated that VEGF-C secretion from hepatocarcinoma cell promoted lymphatic endothelial cell growth through activating extracellular signal-regulated kinase (ERK) signaling. Taken together, this study reveals a novel existence of Heparanase-1/syndecan-1 axis in hepatocarcinoma cell and its roles in the cross-talking with the microenvironment of lymphatic metastasis.

  8. Lymphatic filariasis in the Philippines.

    Science.gov (United States)

    Kron, M; Walker, E; Hernandez, L; Torres, E; Libranda-Ramirez, B

    2000-08-01

    Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout most of the southern half of the Philippine archipelago. Economic and manpower shortages prior to 1996 made it difficult to acquire new prevalence data and vector control data concurrently from all provinces. Nevertheless, analysis of cumulative prevalence data on filariasis indicates the persistence of filariasis in each of the three major island groups - Luzon, Visayas and Mindanao - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize the prevalence data, and review host, parasite and vector characteristics relevant to the design and implementation of disease control initiatives in the Philippines planned for the year 2000.

  9. Urban lymphatic filariasis

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Mwakitalu, Mbutolwe E.

    2013-01-01

    impact. However, with rapid and unplanned growth of cities in the developing world, there is a need also to consider LF transmission and control in urban settings. Here, we review currently available knowledge on urban LF and the environmental and socio-economic basis for its occurrence. Among the three...... and drainage facilities. For this reason, urban LF also often shows a marked focality in distribution, with most cases clustered in areas inhabited by the less privileged city populations. More knowledge on urban LF is needed, in particular on its socio-economic and human behavioural context, on the potential...... parasite species causing LF in humans, only Wuchereria bancrofti has been documented to have a significant potential for urban transmission. This is primarily because one of its vectors, Culex quinquefasciatus, thrives and proliferates excessively in crowded city areas with poor sanitary, sewerage...

  10. Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

    DEFF Research Database (Denmark)

    Robdrup Tinning, Anne; Jensen, Boye L; Johnsen, Iben

    2016-01-01

    . In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria......Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary...... mechanism....

  11. The Importance of Drains for the Larval Development of Lymphatic Filariasis and Malaria Vectors in Dar es Salaam, United Republic of Tanzania

    Science.gov (United States)

    Castro, Marcia C.; Kanamori, Shogo; Kannady, Khadija; Mkude, Sigsbert; Killeen, Gerry F.; Fillinger, Ulrike

    2010-01-01

    Background Dar es Salaam has an extensive drain network, mostly with inadequate water flow, blocked by waste, causing flooding after rainfall. The presence of Anopheles and Culex larvae is common, which is likely to impact the transmission of lymphatic filariasis and malaria by the resulting adult mosquito populations. However, the importance of drains as larval habitats remains unknown. Methodology Data on mosquito larval habitats routinely collected by the Urban Malaria Control Program (UMCP) and a special drain survey conducted in 2006 were used to obtain a typology of habitats. Focusing on drains, logistic regression was used to evaluate potential factors impacting the presence of mosquito larvae. Spatial variation in the proportion of habitats that contained larvae was assessed through the local Moran's I indicator of spatial association. Principal Findings More than 70% of larval habitats in Dar es Salaam were human-made. Aquatic habitats associated with agriculture had the highest proportion of Anopheles larvae presence and the second highest of Culex larvae presence. However, the majority of aquatic habitats were drains (42%), and therefore, 43% (1,364/3,149) of all culicine and 33% (320/976) of all anopheline positive habitats were drains. Compared with drains where water was flowing at normal velocity, the odds of finding Anopheles and Culex larvae were 8.8 and 6.3 (pcontrol efforts of those diseases. PMID:20520797

  12. Avians as a model system of vascular development.

    Science.gov (United States)

    Bressan, Michael; Mikawa, Takashi

    2015-01-01

    For more than 2,000 years, philosophers and scientists have turned to the avian embryo with questions of how life begins (Aristotle and Peck Generations of Animals. Loeb Classics, vol. XIII. Harvard University Press, Cambridge, 1943; Needham, A history of embryology. Abelard-Schuman, New York, 1959). Then, as now, the unique accessibility of the embryo both in terms of acquisition of eggs from domesticated fowl and ease at which the embryo can be visualized by simply opening the shell has made avians an appealing and powerful model system for the study of development. Thus, as the field of embryology has evolved through observational, comparative, and experimental embryology into its current iteration as the cellular and molecular biology of development, avians have remained a useful and practical system of study.

  13. Red light, green light: Signals that control endothelial cell proliferation during embryonic vascular development

    Science.gov (United States)

    The proper regulation of endothelial cell proliferation is critical for vascular development in the embryo. VEGF-A and bFGF, which are important in the induction of mesodermal progenitors to form a capillary plexus, are also key mitogenic signals. Disruption in VEGF-A or bFGF decreases endothelial c...

  14. Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat

    NARCIS (Netherlands)

    Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik J.; de Zeeuw, Dick; Provoost, Abraham P.; van Dokkum, Richard P. E.

    2010-01-01

    Ochodnicky P, Henning RH, Buikema HJ, de Zeeuw D, Provoost AP, van Dokkum RP. Renal vascular dysfunction precedes the development of renal damage in the hypertensive Fawn-Hooded rat. Am J Physiol Renal Physiol 298: F625-F633, 2010. First published December 9, 2009; doi:10.1152/ajprenal.00289.2009.-I

  15. Length-tension relationships of small arteries, veins, and lymphatics from the rat mesenteric microcirculation.

    Science.gov (United States)

    Zhang, Rong-Zhen; Gashev, Anatoliy A; Zawieja, David C; Davis, Michael J

    2007-04-01

    The passive and active length-tension relationships of isolated rat mesenteric lymphatics ( approximately 150 microm ID), and adjacent small arteries ( approximately 240 microm) and veins ( approximately 275 microm) were compared under isometric conditions using a wire myograph. About 60% of the lymphatic vessels developed spontaneous contractions in physiological saline solution at nominal preload. To maximally activate smooth muscle, 145 mM K(+) + 5 x 10(-5) M norepinephrine was used for arteries, and 145 mM K(+) + 1 x 10(-6) M substance P was used for lymphatics and veins. In response, arteries exhibited monotonic force development to a plateau level, whereas lymphatics and veins showed biphasic force development, consisting of a transient force peak followed by partial relaxation to a plateau over approximately 5 min. The passive and the active length-tension curves were similar in shape among all three vessels. However, the maximal active tension of arteries (3.4 +/- 0.42 mN/mm) was significantly greater than peak active tension (0.59 +/- 0.04 mN/mm) or plateau tension (0.20 +/- 0.04 mN/mm) in small veins and greater than peak active tension (0.34 +/- 0.02 mN/mm) or plateau tension (0.21 +/- 0.02 mN/mm) in lymphatics. Maximal active medial wall stress was similar between lymphatics and veins but was approximately fivefold higher in small arteries. For lymphatics, the pressure calculated from the optimal preload was significantly higher than that found previously in isobaric studies of isolated lymphatics, suggesting the capacity to operate at higher than normal pressures for increased responsiveness. Our results represent the first mechanical comparisons of arterial, venous, and lymphatic vessels in the same vasculature.

  16. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Souheil El-Chemaly

    2012-09-01

    Full Text Available The primary function of the lymphatic system is absorbing and transporting macromolecules and immune cells to the general circulation, thereby regulating fluid, nutrient absorption and immune cell trafficking. Lymphangiogenesis plays an important role in tissue inflammation and tumour cell dissemination. Lymphatic involvement is seen in lymphangioleiomyomatosis (LAM and idiopathic pulmonary fibrosis (IPF. LAM, a disease primarily affecting females, involves the lung (cystic destruction, kidney (angiomyolipoma and axial lymphatics (adenopathy and lymphangioleiomyoma. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC. Cystic lung destruction results from proliferation of LAM cells, which are abnormal smooth muscle-like cells with mutations in the TSC1 or TSC2 gene. Lymphatic abnormalities arise from infiltration of LAM cells into the lymphatic wall, leading to damage or obstruction of lymphatic vessels. Benign appearing LAM cells possess metastatic properties and are found in the blood and other body fluids. IPF is a progressive lung disease resulting from fibroblast proliferation and collagen deposition. Lymphangiogenesis is associated with pulmonary destruction and disease severity. A macrophage subset isolated from IPF bronchoalveolar lavage fluid (BALF express lymphatic endothelial cell markers in vitro, in contrast to the same macrophage subset from normal BALF. Herein, we review lymphatic involvement in LAM and IPF.

  17. Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Tugues, Sònia; Fernández-Varo, Guillermo; Held, Kara F; Soria, Guadalupe; Tudela, Raúl; Planas, Anna M; Fernández-Hernando, Carlos; Arroyo, Vicente; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2013-01-01

    The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis. Cirrhosis was induced in rats by CCl(4) inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-N(G)-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage. The upregulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodelling, which is characterised by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.

  18. Mast Cells and Histamine: Do They Influence Placental Vascular Network and Development in Preeclampsia?

    Directory of Open Access Journals (Sweden)

    Grzegorz Szewczyk

    2012-01-01

    Full Text Available The physiological course of pregnancy is closely related to adequate development of the placenta. Shallow invasion of trophoblast as well as decreased development of the placental vascular network are both common features of preeclampsia. To better understand the proangiogenic features of mast cells, in this study we aim to identify the potential relationship between the distribution of mast cells within the placenta and vascular network development. Material and Methods. Placentas from preeclampsia-complicated pregnancies (=11 and from physiological pregnancies (=11 were acquired after cesarean section. The concentration of histamine was measured, and immunohistochemical staining for mast cell tryptase was performed. Morphometric analysis was then performed. Results. We noticed significant differences between the examined groups. Notably, in the preeclampsia group compared to the control group, we observed a higher mean histamine concentration, higher mast cell density (MCD, lower mean mast cell (MMCA and lower vascular/extravascular (V/EVT index. In physiological pregnancies, a positive correlation was observed between the histamine concentration and V/VEVT index as well as MCD and the V/VEVT index. In contrast, a negative correlation was observed between MMCA and the V/EVT index in physiological pregnancies. Conclusions. Based on the data from our study, we suggest that a differential distribution of mast cells and corresponding changes in the concentration of histamine are involved in the defective placental vascularization seen in preeclamptic placentas.

  19. In vivo visualization and quantification of collecting lymphatic vessel contractility using near-infrared imaging

    Science.gov (United States)

    Chong, Chloé; Scholkmann, Felix; Bachmann, Samia B.; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T.

    2016-01-01

    Techniques to image lymphatic vessel function in either animal models or in the clinic are limited. In particular, imaging methods that can provide robust outcome measures for collecting lymphatic vessel function are sorely needed. In this study, we aimed to develop a method to visualize and quantify collecting lymphatic vessel function in mice, and to establish an in vivo system for evaluation of contractile agonists and antagonists using near-infrared fluorescence imaging. The flank collecting lymphatic vessel in mice was exposed using a surgical technique and a near-infrared tracer was infused into the inguinal lymph node. Collecting lymphatic vessel contractility and valve function could be easily visualized after the infusion. A diameter tracking method was established and the diameter of the vessel was found to closely correlate to near-infrared fluorescence signal. Phasic contractility measures of frequency and amplitude were established using an automated algorithm. The methods were validated by tracking the vessel response to topical application of a contractile agonist, prostaglandin F2α, and by demonstrating the potential of the technique for non-invasive evaluation of modifiers of lymphatic function. These new methods will enable high-resolution imaging and quantification of collecting lymphatic vessel function in animal models and may have future clinical applications. PMID:26960708

  20. Tailoring of chronic lymphatic leukemia therapy.

    Science.gov (United States)

    Elhefni, Ashraf M

    2013-01-01

    Chronic lymphocytic leukemia (CLL) remains an incurable disease, with all patients who require therapy destined to relapse and understanding of the pathophysiology of chronic lymphocytic leukemia has advanced significantly. It is now clear that chronic lymphocytic leukemia is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the chronic lymphatic leukemia cell occurs in most, if not all, patients through antigen stimulation via the B cell receptors. In addition, there is now a appreciation of the role of the p53 pathway leading to chemoresistance and the elucidation of the molecular and intracellular signaling mechanisms of disease is just beginning to facilitate the development of several targeted small molecules that promise to revolutionize the treatment of Chronic lymphocytic leukemia.

  1. Testosterone replacement attenuates intimal hyperplasia development in an androgen deficient model of vascular injury.

    Science.gov (United States)

    Freeman, Brian M; Univers, Junior; Fisher, Richard K; Kirkpatrick, Stacy S; Klein, Frederick A; Freeman, Michael B; Mountain, Deidra J H; Grandas, Oscar H

    2017-01-01

    Androgen deficiency (AD) is associated with increased risk of vascular disease. Dysfunctional remodeling of the vessel wall and atypical proliferative potential of vascular smooth muscle cells (VSMCs) are fundamental processes in the development of intimal hyperplasia (IH). We have demonstrated an inverse relationship between dihydrotestosterone (DHT) levels, matrix metalloproteinase activity, and VSMC migration and proliferation in vitro. Here, we investigated the role of AD and testosterone (TST) replacement in IH development in an animal model of vascular injury to elucidate mechanisms modulated by AD that could be playing a role in the development of vascular pathogenesis. Aged orchiectomized male rats underwent TST supplementation via controlled release pellet (0.5-35 mg). Young adult and middle-age adult intact (MI) and orchiectomized placebo (Plac) groups served as controls. All groups underwent balloon angioplasty of the left common carotid at a 14-d post-TST. Carotid tissue was collected at a 14-d post-balloon angioplasty and subjected to morphologic and immunohistochemical analyses. Human male VSMCs were treated with DHT (0-3000 nM) for 24 h then subjected to quantitative PCR for gene expression analyses and costained for F-actin and G-actin for visualization of cytoskeletal organization. I:M ratio was increased in Plac, subphysiological, low-physiological, and high pharmacologic level TST animals compared with MI controls but was decreased with high-physiological TST supplementation. Injury-induced expression of previously defined matrix metalloproteinase remodeling enzymes was not significantly affected by TST status. Urotensin (UTS) receptor (UTSR) staining was low in injured vessels of all young adult intact, MI, and Plac controls but was significantly upregulated in all groups receiving exogenous TST supplementation, irrespective of dose. In vitro DHT exposure increased the expression of UTSR in VSMCs in a dose-dependent manner. However, this did

  2. Dysfunction of pulmonary vascular endothelium in chronic obstructive pulmonary disease: basic considerations for future drug development.

    Science.gov (United States)

    Yang, Qin; Underwood, Malcolm J; Hsin, Michael K Y; Liu, Xiao-Cheng; He, Guo-Wei

    2008-09-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading health problems worldwide and continues to be a major cause of morbidity and mortality in developed countries. The clinical features of COPD are chronic obstructive bronchiolitis and emphysema. Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of COPD at different stages of the disease. Functional changes of pulmonary endothelial cells in COPD include antiplatelet abnormalities, anticoagulant disturbances, endothelial activation, atherogenesis, and compromised regulation of vascular tone which may adversely affect the ventilation-perfusion match in COPD. As the most important risk factor of COPD, cigarette smoking may initiate pulmonary vascular impairment through direct injury of endothelial cells or release of inflammatory mediators. Morphological changes such as denudation of endothelium and endothelial cell apoptosis have been observed in the pulmonary vasculature in COPD patients as well as functional alterations. Changes in the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin, selectins, and adhesion molecules in pulmonary endothelial cells as well as complex regulation and interaction of vasoactive substances and growth factors released from endothelium may underlie the mechanisms of pulmonary endothelial dysfunction in COPD. The mechanism of endothelial repair/regeneration in COPD, although not fully understood, may involve upregulation of vascular endothelial growth factors in the early stages along with an increased number of bone marrow-derived progenitor cells. These factors should be taken into account when developing new strategies for the pharmacological therapy of patients with COPD.

  3. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

    Science.gov (United States)

    Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2013-11-12

    Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P valuesgrowth rates and cardiovascular adaptations in childhood.

  4. Ion channels, guidance molecules, intracellular signaling and transcription factors regulating nervous and vascular system development.

    Science.gov (United States)

    Akita, Tenpei; Kumada, Tatsuro; Yoshihara, Sei-ichi; Egea, Joaquim; Yamagishi, Satoru

    2016-03-01

    Our sophisticated thoughts and behaviors are based on the miraculous development of our complex nervous network system, in which many different types of proteins and signaling cascades are regulated in a temporally and spatially ordered manner. Here we review our recent attempts to grasp the principles of nervous system development in terms of general cellular phenomena and molecules, such as volume-regulated anion channels, intracellular Ca(2+) and cyclic nucleotide signaling, the Npas4 transcription factor and the FLRT family of axon guidance molecules. We also present an example illustrating that the same FLRT family may regulate the development of vascular networks as well. The aim of this review is to open up new vistas for understanding the intricacy of nervous and vascular system development.

  5. Placental development during early pregnancy in sheep: Effects of embryo origin on vascularization

    Science.gov (United States)

    Grazul-Bilska, Anna T.; Johnson, Mary Lynn; Borowicz, Pawel P.; Bilski, Jerzy J.; Cymbaluk, Taylor; Norberg, Spencer; Redmer, Dale A.; Reynolds, Lawrence P.

    2014-01-01

    Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from natural mating (NAT-ET), or in vitro fertilization (IVF) or activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared to NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM), and for NAT-ET, IVF and IVA in CAR. In FM, mRNA expression was decreased (P<0.01–0.08) in NAT-ET, IVF and IVA compared to NAT for vascular endothelial growth factor (VEGF) and its receptor FLT-1, placental growth factor (PGF), neuropilin (NP) 1 and 2, angiopoietin (ANGPT) 1 and 2, endothelial nitric oxide synthase (NOS3), hypoxia inducible factor-1A (HIF1A), fibroblast growth factor (FGF) 2 and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01–0.05) in NAT-ET, IVF and IVA compared to NAT for VEGF, FLT-1, PGF, ANGPT1 and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development. PMID:24472816

  6. Type 1 and 3 inositol trisphosphate receptors are required for extra-embryonic vascular development.

    Science.gov (United States)

    Uchida, Keiko; Nakazawa, Maki; Yamagishi, Chihiro; Mikoshiba, Katsuhiko; Yamagishi, Hiroyuki

    2016-10-01

    The embryonic-maternal interface of the placental labyrinth, allantois, and yolk sac are vital during embryogenesis; however, the precise mechanism underlying the vascularization of these structures remains unknown. Herein we focus on the role of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), which are intracellular Ca(2+) release channels, in placentation. Double knockout (DKO) of type 1 and 3 IP3Rs (IP3R1 and IP3R3, respectively) in mice resulted in embryonic lethality around embryonic day (E) 11.5. Because IP3R1 and IP3R3 were co-expressed in endothelial cells in the labyrinth, allantois, and yolk sac, we investigated extra-embryonic vascular development in IP3R1- and IP3R3-DKO mice. The formation of chorionic plates and yolk sac vessels seemed dysregulated around the timing of the chorio-allantoic attachment, immediately followed by the disorganization of allantoic vessels, the decreased expression of the spongiotrophoblast cell marker Tpbpa and the growth retardation of the embryos in DKO mice. Fluorescent immunohistochemistry demonstrated downregulation of a vascular endothelial marker, CD31, in labyrinth embryonic vessels and poor elongation of extra-embryonic mesoderm into the labyrinth layer in DKO placenta, whereas the branching of the DKO chorionic trophoblast was initiated. In addition, allantoic and yolk sac vessels in extra-embryonic tissues were less remodeled in DKO mice. In vitro endothelial cord formation and migration activities of cultured vascular endothelial cells derived from human umbilical vein were downregulated under the inhibition of IP3R. Our results suggest that IP3R1 and IP3R3 are required for extra-embryonic vascularization in the placenta, allantois, and yolk sac. This is the first demonstration of the essential role of IP3/IP3Rs signaling in the development of the vasculature at the embryonic-maternal interface.

  7. Stabiliztin of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 is Critical for Vascular Development

    Energy Technology Data Exchange (ETDEWEB)

    Y He; H Zhang; L Yu; M Gunel; T Boggon; H Chen; W Min

    2011-12-31

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an early embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.

  8. Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development.

    Science.gov (United States)

    Chouinard-Pelletier, Guillaume; Jahnsen, Espen D; Jones, Elizabeth A V

    2013-01-01

    Vascular development is believed to occur first by vasculogenesis followed by angiogenesis. Though angiogenesis is the formation of new vessels, we found that vascular density actually decreases during this second stage. The onset of the decrease coincided with the entry of erythroblasts into circulation. We therefore measured the level of shear stress at various developmental stages and found that it was inversely proportional to vascular density. To investigate whether shear stress was inhibitory to angiogenesis, we altered shear stress levels either by preventing erythroblasts from entering circulation ("low" shear stress) or by injection of a starch solution to increase the blood plasma viscosity ("high" shear stress). By time-lapse microscopy, we show that reverse intussusception (merging of two vessels) is inversely proportional to the level of shear stress. We also found that angiogenesis (both sprouting and splitting) was inversely proportional to shear stress levels. These effects were specific to the arterial or venous plexus however, such that the effect on reverse intussusception was present only in the arterial plexus and the effect on sprouting only in the venous plexus. We cultured embryos under altered shear stress in the presence of either DAPT, a Notch inhibitor, or DMH1, an inhibitor of the bone morphogenetic protein (BMP) pathway. DAPT treatment phenocopied the inhibition of erythroblast circulation ("low" shear stress) and the effect of DAPT treatment could be partially rescued by injection of starch. Inhibition of the BMP signaling prevented the reduction in vascular density that was observed when starch was injected to increase shear stress levels.

  9. Quantifying three-dimensional rodent retina vascular development using optical tissue clearing and light-sheet microscopy

    Science.gov (United States)

    Singh, Jasmine N.; Nowlin, Taylor M.; Seedorf, Gregory J.; Abman, Steven H.; Shepherd, Douglas P.

    2017-07-01

    Retinal vasculature develops in a highly orchestrated three-dimensional (3-D) sequence. The stages of retinal vascularization are highly susceptible to oxygen perturbations. We demonstrate that optical tissue clearing of intact rat retinas and light-sheet microscopy provides rapid 3-D characterization of vascular complexity during retinal development. Compared with flat mount preparations that dissect the retina and primarily image the outermost vascular layers, intact cleared retinas imaged using light-sheet fluorescence microscopy display changes in the 3-D retinal vasculature rapidly without the need for point scanning techniques. Using a severe model of retinal vascular disruption, we demonstrate that a simple metric based on Sholl analysis captures the vascular changes observed during retinal development in 3-D. Taken together, these results provide a methodology for rapidly quantifying the 3-D development of the entire rodent retinal vasculature.

  10. [Formation of the vascular system of developing bean (Phaseolus limensis L.) seeds according to nuclear magnetic resonance microtomography].

    Science.gov (United States)

    Vinogradova, I S; Falaleev, O V

    2012-01-01

    1H magnetic resonance microtomography imaging was applied to study vascular systems in developing bean (Phaseolus limensis L.) seeds. Using the gradient echo method, we recorded 2D tomographic sections in the sagittal and axial planes of the fruits sampled from a vegetating plant on days 10, 17, 24, and 31 after fertilization. Any vascular connection between the tissues of maternal plant (bean pod and seed coat) and the embryo were undetectable. The embryo has an autonomous branched network of procambial strands in the cotyledons, converging to the embryonic axis. The bean pods are covered with a network of vascular bundles; large vascular strands run along the dorsal and ventral sutures. The seed coat vascular bundles are formed in the process of seed ripening and are represented by a developed vascular system multiply branching in the middle part of the ground parenchyma at the stage of physiological maturity. They are connected with the source of assimilates via the lateral pod veins and a large vascular bundle, entering the seed below the hilum via the placenta. Assimilates enter the external part of the seed coat, which contains no vascular bundles, via the funiculus vascular bundles and hilum tissue.

  11. Vacuum-assisted wound closure in vascular surgery - clinical and cost benefits in a developing country

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    Končar Igor

    2016-01-01

    Full Text Available Background/Aim. Surgical and chronic wounds in vascular patients might contribute to limb loss and death. Vacuum-assisted closure (VAC - Kinetic Concepts, Inc. (KCI, has been increasingly used in Western Europe and the USA clinical practice for 15 years. Advantages of this method are faster wound healing, wound approximation, lower wound related treatment costs and improved quality of life during treatment. Evidence related to the usage of VAC therapy in vascular patients and cost effectiveness of VAC therapy in a developing country are lacking. The aim of this study was to explore results of VAC therapy in vascular surgery comparing to conventional methods and to test cost effects in a developing country like Serbia. Methods. All patients with wound infection or dehiscence operated at the tertiary vascular university clinic in the period from January 2011 - January 2012, were treated with VAC therapy. The primary endpoint was wound closure, while secondary endpoints were hospital stay, the number of weekly dressings, costs of wound care, working time of medical personnel. The patients were divided into groups according to the wound type and location: wound with exposed synthetic vascular implant (25%, laparotomy (13%, foot amputation (29%, major limb amputation (21%, fasciotomy (13%. The results of primary and secondary endpoint were compared with the results of conventional treatment during the previous year. Results. There was one death (1/42, 2.38% and one limb loss (1/12, 2.38% in the VAC group, and 8 deaths (8/38, 21.05% and 5 (5/38, 13.15% limb losses in the patients treated with conventional therapy. In the VAC group there was one groin bleeding (1/12, 2.38%, one groin reinfection (1/12, 2.38% and one resistance to therapy with a consequent limb loss. Costs of hospital stay (p < 0.001 and nursing time (p < 0.001 were reduced with VAC therapy in the group with exposed graft. Conclusion. VAC therapy is the effective method for care of

  12. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  13. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  14. B lymphocyte-specific c-Myc expression stimulates early and functional expansion of the vasculature and lymphatics during lymphomagenesis.

    Science.gov (United States)

    Ruddell, Alanna; Mezquita, Pau; Brandvold, Kimberly A; Farr, Andrew; Iritani, Brian M

    2003-12-01

    Expression of the c-myc proto-oncogene is deregulated in many human cancers. We examined the role of c-Myc in stimulating angiogenesis and lymphangiogenesis in a highly metastatic murine model of Burkitt's lymphoma (E micro -c-myc), where c-Myc is expressed exclusively in B lymphocytes. Immunohistochemical analysis of bone marrow and lymph nodes from young (preneoplastic) E micro -c-myc transgenic mice revealed increased growth of blood vessels, which are functional by dye flow assay. Lymphatic sinuses also increased in size and number within the lymph nodes, as demonstrated by immunostaining for with a lymphatic endothelial marker 10.1.1. The 10.1.1 antibody recognizes VEGFR-2- and VEGFR-3-positive lymphatic sinuses and vessels within lymph nodes, and also recognizes lymphatic vessels in other tissues. Subcutaneously injected dye traveled more efficiently through draining lymph nodes in E micro -c-myc mice, indicating that these hypertrophic lymphatic sinuses increase lymph flow. Purified B lymphocytes and lymphoid tissues from E micro -c-myc mice expressed increased levels of vascular endothelial growth factor (VEGF) by immunohistochemical or immunoblot assays, which could promote blood and lymphatic vessel growth through interaction with VEGFR-2, which is expressed on the endothelium of both vessel types. These results indicate that constitutive c-Myc expression stimulates angiogenesis and lymphangiogenesis, which may promote the rapid growth and metastasis of c-Myc-expressing cancer cells, respectively.

  15. Vascular thoracic outlet syndrome developed after minimally invasive repair of pectus excavatum.

    Science.gov (United States)

    Kılıç, Burcu; Demirkaya, Ahmet; Turna, Akif; Kaynak, Kamil

    2013-09-01

    The Nuss procedure is a minimally invasive surgical repair technique for pectus excavatum with fewer delayed complications compared to open procedures. We report the case of a 22-year-old man with deep pectus excavatum who developed vascular thoracic outlet syndrome after the Nuss procedure. Further evaluation demonstrated that the first rib was causing severe obstruction of the right subclavian artery. The patient showed clinical features of subclavian artery compression. A first rib resection, division of the anterior scalene muscle and fibrous bands provided complete relief of the complaints. The forced structural and spatial changes produced by the elevation of the depressed upper chest might have caused this complication. Vascular thoracic outlet syndrome should be kept in mind as a possible complication in patients who have undergone minimally invasive repair of pectus excavatum, and this complication can be treated by first rib resection.

  16. Sensorineural hearing loss and ischemic injury: Development of animal models to assess vascular and oxidative effects.

    Science.gov (United States)

    Olivetto, E; Simoni, E; Guaran, V; Astolfi, L; Martini, A

    2015-09-01

    Hearing loss may be genetic, associated with aging or exposure to noise or ototoxic substances. Its aetiology can be attributed to vascular injury, trauma, tumours, infections or autoimmune response. All these factors could be related to alterations in cochlear microcirculation resulting in hypoxia, which in turn may damage cochlear hair cells and neurons, leading to deafness. Hypoxia could underlie the aetiology of deafness, but very few data about it are presently available. The aim of this work is to develop animal models of hypoxia and ischemia suitable for study of cochlear vascular damage, characterizing them by electrophysiology and gene/protein expression analyses. The effects of hypoxia in infarction were mimicked in rat by partial permanent occlusion of the left coronary artery, and those of ischemia in thrombosis by complete temporary carotid occlusion. In our models both hypoxia and ischemia caused a small but significant hearing loss, localized at the cochlear apex. A slight induction of the coagulation cascade and of oxidative stress pathways was detected as cell survival mechanism, and cell damages were found on the cuticular plate of outer hair cells only after carotid ischemia. Based on these data, the two developed models appear suitable for in vivo studies of cochlear vascular damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Prospects for Vascular Access Education in Developing Countries: Current Situation in Cambodia.

    Science.gov (United States)

    Naganuma, Toshihide; Takemoto, Yoshiaki

    2017-09-05

    We report our activities training doctors on vascular access procedures at International University (IU) Hospital in Cambodia through a program facilitated by Ubiquitous Blood Purification International, a nonprofit organization that provides medical support to developing countries in the field of dialysis medicine. Six doctors from Japan have been involved in the education of medical personnel at IU, and we have collectively visited Cambodia about 15 times from 2010 to 2016. In these visits, we have performed many operations, including 42 for arteriovenous fistula, 1 arteriovenous graft, and 1 percutaneous transluminal angioplasty. Stable development and management of vascular access is increasingly required in Cambodia due to increased use of dialysis therapy, and training of doctors in this technique is urgently required. However, we have encountered several difficulties that need to be addressed, including (1) the situation of personnel receiving this training, (2) problems with facilities, including medical equipment and drugs, (3) financial limitations, and (4) problems with management of vascular access. © 2017 S. Karger AG, Basel.

  18. Development of Decellularized Human Umbilical Arteries as Small-Diameter Vascular Grafts

    Science.gov (United States)

    Gui, Liqiong; Muto, Akihito; Chan, Stephen A.; Breuer, Christopher K.

    2009-01-01

    Objective Developing a tissue-engineered small-diameter (<6 mm) vascular graft for reconstructive surgery has remained a challenge for the past several decades. This study was conducted to develop a decellularized umbilical artery and to evaluate its composition, endothelial cell compatibility, mechanical properties, and in vivo stability for potential use as a small-diameter vascular graft. Methods and Results Human umbilical arteries were isolated and decellularized by incubation in CHAPS and sodium dodecyl sulfate buffers followed by incubation in endothelial growth media-2. Decellularized umbilical arteries were completely devoid of cellular and nuclear material while retaining the integrity of extracellular collagenous matrix. The mechanical strength of the decellularized umbilical artery as assessed by its burst pressure in vitro showed no significant change from its native form. Decellularized umbilical arteries supported endothelial adherence as indicated by the re-endotheliazation with a monolayer of human umbilical vein endothelial cells. Furthermore, decellularized vessels that were implanted into nude rats as abdominal aorta interposition grafts remained mechanically intact and patent for up to 8 weeks. Conclusion Decellularized human umbilical arteries preserved the extracellular matrix, supported endothelialization, and retained function in vivo for up to 8 weeks. These properties suggest the potential use of decellularized umbilical arteries as small-diameter vascular grafts. PMID:19207043

  19. Pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis in tumor lymphangiogenesis and lymphatic metastasis.

    Science.gov (United States)

    Wang, Jingwen; Huang, Yuhong; Zhang, Jun; Wei, Yuanyi; Mahoud, Salma; Bakheet, Ahmed Musa Hago; Wang, Li; Zhou, Shuting; Tang, Jianwu

    2016-10-01

    Precondition for tumor lymphatic metastasis is that tumor cells induce formation of original and newborn lymphatic vessels and invade surrounding lymphatic vessels in tumor stroma, while some pathway-related molecules play an important role in mechanisms associated with proliferation and migration of lymphatic endothelial cells (LECs) and tumor cells. In lymphangiogenesis and lymphatic metastasis, the pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, such as Furin-like enzyme, CNTN1, Prox1, LYVE-1, Podoplanin, SOX18, SDF1 and CXCR4, are direct constitutors as a portion of VEGFC/D-VEGFR3/NRP2 axis, and their biological activities rely on this ligand-receptor system. These axis-related signal molecules could gradually produce waterfall-like cascading effects, mediate differentiation and maturation of LECs, remodel original and neonatal lymphatic vessels, as well as ultimately promote tumor cell chemotaxis, migration, invasion and metastasis to lymphoid tracts. This review summarizes the structure and function features of pathway-related molecules of VEGFC/D-VEGFR3/NRP2 axis, the expression changes of these molecules in different anatomic organs or histopathologic types or development stages of various tumors, the characteristics of transduction, implementation, integration of signal networks, the interactive effects on biological behaviors between tumor cells and lymphatic endothelial cells, and their molecular mechanisms and significances in tumor lymphangiogenesis and lymphatic metastasis.

  20. Connexins in lymphatic vessel physiology and disease.

    Science.gov (United States)

    Meens, Merlijn J; Sabine, Amélie; Petrova, Tatiana V; Kwak, Brenda R

    2014-04-17

    Connexins are transmembrane proteins that form gap junction- and hemi-channels. Once inserted into the membrane, hemi-channels (connexons) allow for diffusion of ions and small molecules (Gap junction channels allow diffusion of similar molecules between the cytoplasms of adjacent cells. The expression and function of connexins in blood vessels has been intensely studied in the last few decades. In contrast, only a few studies paid attention to lymphatic vessels; convincing in vivo data with respect to expression patterns of lymphatic connexins and their functional roles have only recently begun to emerge. Interestingly, mutations in connexin genes have been linked to diseases of lymphatic vasculature, most notably primary and secondary lymphedema. This review summarizes the available data regarding lymphatic connexins. More specifically it addresses (i) early studies aimed at presence of gap junction-like structures in lymphatic vessels, (ii) more recent studies focusing on lymphatic connexins using genetically engineered mice, and (iii) results of clinical studies that have reported lymphedema-linked mutations in connexin genes. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs.

    Directory of Open Access Journals (Sweden)

    Mansoor A Syed

    Full Text Available The role of vascular endothelial growth factor (VEGF-induced 3 different nitric oxide synthase (NOS isoforms in lung development and injury in the newborn (NB lung are not known. We hypothesized that VEGF-induced specific NOS pathways are critical regulators of lung development and injury.We studied NB wild type (WT, lung epithelial cell-targeted VEGF165 doxycycline-inducible overexpressing transgenic (VEGFTG, VEGFTG treated with a NOS1 inhibitor (L-NIO, VEGFTG x NOS2-/- and VEGFTG x NOS3+/- mice in room air (RA for 7 postnatal (PN days. Lung morphometry (chord length, vascular markers (Ang1, Ang2, Notch2, vWF, CD31 and VE-cadherin, cell proliferation (Ki67, vascular permeability, injury and oxidative stress markers (hemosiderin, nitrotyrosine and 8-OHdG were evaluated.VEGF overexpression in RA led to increased chord length and vascular markers at PN7, which were significantly decreased to control values in VEGFTG x NOS2-/- and VEGFTG x NOS3+/- lungs. However, we found no noticeable effect on chord length and vascular markers in the VEGFTG / NOS1 inhibited group. In the NB VEGFTG mouse model, we found VEGF-induced vascular permeability in the NB murine lung was partially dependent on NOS2 and NOS3-signaling pathways. In addition, the inhibition of NOS2 and NOS3 resulted in a significant decrease in VEGF-induced hemosiderin, nitrotyrosine- and 8-OHdG positive cells at PN7. NOS1 inhibition had no significant effect.Our data showed that the complete absence of NOS2 and partial deficiency of NOS3 confers protection against VEGF-induced pathologic lung vascular and alveolar developmental changes, as well as injury markers. Inhibition of NOS1 does not have any modulating role on VEGF-induced changes in the NB lung. Overall, our data suggests that there is a significant differential regulation in the NOS-mediated effects of VEGF overexpression in the developing mouse lung.

  2. MiR-221 and miR-130a regulate lung airway and vascular development.

    Directory of Open Access Journals (Sweden)

    Sana Mujahid

    Full Text Available Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

  3. Insulin resistance and adipose tissue in the development of vascular diseases in high-risk patients

    NARCIS (Netherlands)

    Gorter, P.M.

    2008-01-01

    The work in this thesis focused on the relationship between presence of insulin resistance and advanced vascular damage in patients with manifest atherosclerotic vascular disease, and on the occurrence of (new) vascular events in insulin resistant patients with and without evident vascular disease.

  4. Mapping the distinctive populations of lymphatic endothelial cells in different zones of human lymph nodes.

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    Saem Mul Park

    Full Text Available The lymphatic sinuses in human lymph nodes (LNs are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs. A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs; in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.

  5. Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides

    Science.gov (United States)

    Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

    2013-01-01

    Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nm) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P= 0.01, n= 7) and 2.7 ± 0.8-fold (P= 0.07, n= 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P= 0.005) and frequency (P= 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion. PMID:23897233

  6. Longitudinal monitoring of head and neck lymphatics in response to cancer treatment

    Science.gov (United States)

    Rasmussen, John C.; Tan, I.-Chih; Naqvi, Syed; Aldrich, Melissa B.; Maus, Erik A.; Blanco, Angel I.; Karni, Ron J.; Sevick-Muraca, Eva M.

    2017-02-01

    Radiation therapy (RT) can promote anti-tumoral responses, but is also known to cause lymphatic endothelial cell apoptosis, loss of dermal lymphatics, and reduction in lymph transport to draining lymph node basins. When combined with lymph node dissection (LND), the radiogenic lymphatic disruption may possibly result in lymph stasis and dermal backflow. If not resolved, this disruption may lead to chronic inflammation, edema, fibrosis, adipose tissue deposition, and ultimately to functional deficits and disfigurement. Because the head and neck (HN) region contains 1/3 of the body's lymph nodes, lymphatic responses to cancer progression and therapy may be significant. Furthermore, it may not be surprising that lymphedema has been estimated to impact as many as 75% of HN cancer survivors three months or more after LND and RT. In this study, we used near-infrared fluorescence imaging to longitudinally assess the lymphatics of 18 patients undergoing treatment for cancer of the oral cavity, oropharynx, and/or larynx following intraoral and intradermal injections of ICG. Patients were imaged before and after surgery, before and after fractionated RT for up to 100 weeks after treatments. Patients who underwent both LND and RT developed lymphatic dermal backflow on treated sides ranging from days after the start of RT to weeks after its completion, while contralateral regions that were not associated with LND but also treated with RT, experienced no such changes in functional lymphatic anatomies. The results show for the first time, the striking reorganization of the lymphatic vasculature and may enable early diagnosis of HN lymphedema.

  7. The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells

    Institute of Scientific and Technical Information of China (English)

    Huanling Yao; Tianshi Wang; Jiexin Deng; Ding Liu; Xiaofei Li; Jinbo Deng

    2014-01-01

    Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.

  8. Vascular endothelial and smooth muscle cell culture on NaOH-treated poly(epsilon-caprolactone) films: a preliminary study for vascular graft development.

    Science.gov (United States)

    Serrano, María Concepción; Portolés, María Teresa; Vallet-Regí, María; Izquierdo, Isabel; Galletti, Lorenzo; Comas, Juan Valentín; Pagani, Raffaella

    2005-05-23

    Tissue engineering offers the potential of providing vessels that can be used to replace diseased and damaged native blood vessels. The endothelization of a synthetic vascular graft minimizes the failures associated with blood clotting and platelet activation. The aim of this study was to culture vascular-derived endothelial and smooth muscle cells on both untreated and NaOH-treated poly(epsilon-caprolactone) (PCL) films, a biocompatible and bio-resorbable polymer, and to evaluate the behavior of both cell types as a preliminary study for vascular graft development. PCL films were prepared by hot pressing; characterized by DSC, IR, SEM, and scanning force microscopy; and treated with NaOH to increase the surface hydrophilicity before cell culture. Endothelial and smooth muscle cells, isolated from pig cava vein, were characterized by immunofluorescence and confocal microscopy studies of endothelial nitric oxide synthase and alpha-smooth muscle actin. Good adhesion, growth, viability and morphology of both the endothelial and smooth muscle cells on PCL films were obtained, but a light stimulation of mitochondrial activity was observed during short culture times. NaOH treatment improved the adhesion and enhanced the proliferation in both cell types. This verified the possible use of this modified polymer as a support in the preparation of a synthetic vascular graft. [Diagram: see text] SEM micrograph of smooth muscle cells cultured on NaOH-treated PCL film. (Original magnification: 1000x).

  9. Development of a Vascularized Skin Construct Using Adipose-Derived Stem Cells from Debrided Burned Skin

    Directory of Open Access Journals (Sweden)

    Rodney K. Chan

    2012-01-01

    Full Text Available Large body surface area burns pose significant therapeutic challenges. Clinically, the extent and depth of burn injury may mandate the use of allograft for temporary wound coverage while autografts are serially harvested from the same donor areas. The paucity of donor sites in patients with burns involving large surface areas highlights the need for better skin substitutes that can achieve early and complete coverage and retain normal skin durability with minimal donor requirements. We have isolated autologous stem cells from the adipose layer of surgically debrided burned skin (dsASCs, using a point-of-care stem cell isolation device. These cells, in a collagen—polyethylene glycol fibrin-based bilayer hydrogel, differentiate into an epithelial layer, a vascularized dermal layer, and a hypodermal layer. All-trans-retinoic acid and fenofibrate were used to differentiate dsASCs into epithelial-like cells. Immunocytochemical analysis showed a matrix- and time-dependent change in the expression of stromal, vascular, and epithelial cell markers. These results indicate that stem cells isolated from debrided skin can be used as a single autologous cell source to develop a vascularized skin construct without culture expansion or addition of exogenous growth factors. This technique may provide an alternative approach for cutaneous coverage after extensive burn injuries.

  10. Lymphatic Vessel Function and Lymphatic Growth Factor Secretion after Microvascular Lymph Node Transfer in Lymphedema Patients

    Directory of Open Access Journals (Sweden)

    Tiina P. Viitanen, MD

    2013-05-01

    Conclusions: Reconstructing the lymphatic anatomy of the axilla with a lymph node flap may offer possibilities that other reconstructive options are lacking. However, we will need further reports and comparative studies about the clinical efficacy of this new promising technique. In addition to the transferred lymph nodes, lymphatic growth factor production may also be induced by other factors related to microvascular breast reconstruction.

  11. Superselective retrograde lymphatic duct embolization for management of postoperative lymphatic leak.

    Science.gov (United States)

    Arslan, Bülent; Masrani, Abdulrahman; Tasse, Jordan Cameron; Stenson, Kerstin; Turba, Ülkü Cenk

    2017-01-01

    Lymphatic leak is a well-documented complication following neck dissection surgeries. When conservative methods fail to control the leak, thoracic duct embolization becomes an option. Transabdominal access is the standard for this procedure; however, it is not always feasible. We discuss a technique of selective lymphatic vessel embolization utilizing retrograde transvenous access.

  12. A brief history of the TDIF-PXY signalling module: balancing meristem identity and differentiation during vascular development.

    Science.gov (United States)

    Etchells, J Peter; Smit, Margot E; Gaudinier, Allison; Williams, Clara J; Brady, Siobhan M

    2016-01-01

    474 I. 474 II. 475 III. 475 IV. 477 V. 477 VI. 477 VII. 479 VIII. 481 482 References 482 SUMMARY: A significant proportion of terrestrial biomass is constituted of xylem cells that make up woody plant tissue. Xylem is required for water transport, and is present in the vascular tissue with a second conductive tissue, phloem, required primarily for nutrient transport. Both xylem and phloem are derived from cell divisions in vascular meristems known as the cambium and procambium. One major component that influences several aspects of plant vascular development, including cell division in the vascular meristem, vascular organization and differentiation of vascular cell types, is a signalling module characterized by a peptide ligand called TRACHEARY ELEMENT DIFFERENTIATION INHIBITORY FACTOR (TDIF) and its cognate receptor, PHLOEM INTERCALATED WITH XYLEM (PXY). In this review, we explore the literature that describes signalling components, phytohormones and transcription factors that interact with these two central factors, to control the varying outputs required in vascular tissues for normal organization and elaboration of plant vascular tissue.

  13. [Effect of premature birth on retinal vascular development in the neonatal rat].

    Science.gov (United States)

    Yang, Xiang-min; Li, Rong; Wang, Yu-sheng; Chu, Zhao-jie; Gao, Xiang

    2013-08-01

    To study the effects of premature birth on the development of rat retinal vasculature. Experimental study. Sixty pregnant Sprague-Dawley rats were divided into four groups: bacterial lipopolysaccharide-induced preterm group (LPS group), RU-486 induced preterm group (RP group), cesarean section induced preterm group (CP group), and the normal delivery rats as the control group. The weight of rats from each group was recorded until postnatal day 21. On postnatal day 4, 7, 10 and 14 (P4, P7, P10 and P14), the retina of right eye was dissected and whole-mounted. Each premature group was divided into two subgroups based on the number of rats in each litter, the small subgroup (6-8 rats per litter, group 1) and the large subgroup (14-18 rats per litter, group 2). The development of retinal vascularization process was observed on P4, P7 and P10 (n = 6).Independent t test, one-way ANOVA and LSD-t test were used to analyzed the results. The weight of premature rats in LPS, CP and RP groups was significantly lower than that in the normal group within postnatal 21 days (LSD-t test: all P premature rats have lower weight and much slower rate of early retinal vascularization, as compared with the normal rats. Furthermore, in the premature rats, the proportion of retinal vascularization in larger litters is less than that in smaller litters. These results indicate that premature birth and larger litter size have effects on the development of rat retinal vasculature.

  14. ETS transcription factor ETV2/ER71/Etsrp in Hematopoietic and Vascular Development, Injury and Regeneration.

    Science.gov (United States)

    Zhao, Haiyong; Xu, Canxin; Lee, Taejin; Liu, Fang; Choi, Kyunghee

    2016-12-27

    Editorial Notice: ETS transcription factor ETV2/ER71/Etsrp in Hematopoietic and Vascular Development, Injury and Regeneration. Haiyong Zhao, Canxin Xu, Taejin Lee, Fang Liu and Kyunghee Choi. Accepted manuscript online: 27 DEC 2016 | DOI: 10.1002/dvdy.24483. The above article, published as an Accepted Article online on Dec 27, 2016, in Wiley Online Library (wileyonlinelibrary.com), has been temporarily withdrawn by agreement between the authors, the journal Editor in Chief, Parker B. Antin, and Wiley Periodicals, Inc. The temporary withdrawal has been agreed due to a delay in publication of an article which is referenced in the above manuscript. This article is protected by copyright. All rights reserved.

  15. Quantitative immunohistochemical assessment of blood and lymphatic microcirculation in cutaneous lichen planus lesions.

    Science.gov (United States)

    Výbohová, Desanka; Mellová, Yvetta; Adamicová, Katarína; Adamkov, Marián; Hešková, Gabriela

    2015-06-01

    Latest advances have brought to light the hypothesis that angiogenesis and lymphangiogenesis are tightly connected to some chronic inflammatory diseases. The present study focuses on immunohistochemical assessment of the quantitative changes in the blood and lymphatic microcirculatory bed in common chronic dermatosis - cutaneous lichen planus. Double immunohistochemistry with CD34 and podoplanin antibodies was used to detect blood and lymphatic endothelium, while anti-human VEGF was used for the observation of a key angiogenesis and lymphangiogenesis inducer. Morphometric analysis was performed with QuickPhoto Micro image analysis software. Results confirmed statistically significant enlargement of both the blood and lymphatic microcirculatory beds. Compared to healthy skin, cutaneous lichen planus lesions revealed 1.6 times enlarged blood microcirculatory bed and 1.8 times enlarged lymphatic microcirculatory bed. Vascular endothelial growth factor (VEGF) expression in lesional skin was significantly higher in the epidermis (19.1 times increase) than in the dermis (10.3 times increase). These findings indicate a tight association of angiogenesis and lymphangiogenesis with the pathogenesis of cutaneous lichen planus.

  16. Histology atlas of the developing mouse hepatobiliary hemolymphatic vascular system with emphasis on embryonic days 11.5-18.5 and early postnatal development

    Science.gov (United States)

    A critical event in fetal development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has lead pathologists and scientists to utilize transgenic mice to identify developmental disorders associated with the hepatobiliary vascular system. Va...

  17. Vascular Occlusions in Grapevines with Pierce’s Disease Make Disease Symptom Development Worse1[OA

    Science.gov (United States)

    Sun, Qiang; Sun, Yuliang; Walker, M. Andrew; Labavitch, John M.

    2013-01-01

    Vascular occlusions are common structural modifications made by many plant species in response to pathogen infection. However, the functional role(s) of occlusions in host plant disease resistance/susceptibility remains controversial. This study focuses on vascular occlusions that form in stem secondary xylem of grapevines (Vitis vinifera) infected with Pierce’s disease (PD) and the impact of occlusions on the hosts’ water transport and the systemic spread of the causal bacterium Xylella fastidiosa in infected vines. Tyloses are the predominant type of occlusion that forms in grapevine genotypes with differing PD resistances. Tyloses form throughout PD-susceptible grapevines with over 60% of the vessels in transverse sections of all examined internodes becoming fully blocked. By contrast, tylose development was mainly limited to a few internodes close to the point of inoculation in PD-resistant grapevines, impacting only 20% or less of the vessels. The extensive vessel blockage in PD-susceptible grapevines was correlated to a greater than 90% decrease in stem hydraulic conductivity, compared with an approximately 30% reduction in the stems of PD-resistant vines. Despite the systemic spread of X. fastidiosa in PD-susceptible grapevines, the pathogen colonized only 15% or less of the vessels in any internode and occurred in relatively small numbers, amounts much too small to directly block the vessels. Therefore, we concluded that the extensive formation of vascular occlusions in PD-susceptible grapevines does not prevent the pathogen’s systemic spread in them, but may significantly suppress the vines’ water conduction, contributing to PD symptom development and the vines’ eventual death. PMID:23292789

  18. Vascular occlusions in grapevines with Pierce's disease make disease symptom development worse.

    Science.gov (United States)

    Sun, Qiang; Sun, Yuliang; Walker, M Andrew; Labavitch, John M

    2013-03-01

    Vascular occlusions are common structural modifications made by many plant species in response to pathogen infection. However, the functional role(s) of occlusions in host plant disease resistance/susceptibility remains controversial. This study focuses on vascular occlusions that form in stem secondary xylem of grapevines (Vitis vinifera) infected with Pierce's disease (PD) and the impact of occlusions on the hosts' water transport and the systemic spread of the causal bacterium Xylella fastidiosa in infected vines. Tyloses are the predominant type of occlusion that forms in grapevine genotypes with differing PD resistances. Tyloses form throughout PD-susceptible grapevines with over 60% of the vessels in transverse sections of all examined internodes becoming fully blocked. By contrast, tylose development was mainly limited to a few internodes close to the point of inoculation in PD-resistant grapevines, impacting only 20% or less of the vessels. The extensive vessel blockage in PD-susceptible grapevines was correlated to a greater than 90% decrease in stem hydraulic conductivity, compared with an approximately 30% reduction in the stems of PD-resistant vines. Despite the systemic spread of X. fastidiosa in PD-susceptible grapevines, the pathogen colonized only 15% or less of the vessels in any internode and occurred in relatively small numbers, amounts much too small to directly block the vessels. Therefore, we concluded that the extensive formation of vascular occlusions in PD-susceptible grapevines does not prevent the pathogen's systemic spread in them, but may significantly suppress the vines' water conduction, contributing to PD symptom development and the vines' eventual death.

  19. VEGF-releasing suture material for enhancement of vascularization: development, in vitro and in vivo study.

    Science.gov (United States)

    Bigalke, Christian; Luderer, Frank; Wulf, Katharina; Storm, Thilo; Löbler, Marian; Arbeiter, Daniela; Rau, Bettina M; Nizze, Horst; Vollmar, Brigitte; Schmitz, Klaus-Peter; Klar, Ernst; Sternberg, Katrin

    2014-12-01

    As it has been demonstrated that bioactive substances can be delivered locally using coated surgical suture materials, the authors developed a vascular endothelial growth factor (VEGF)-releasing suture material that should promote vascularization and potentially wound healing. In this context, the study focused on the characterization of the developed suture material and the verification of its biological activity, as well as establishing a coating process that allows reproducible and stable coating of a commercially available polydioxanone suture material with poly(l-lactide) (PLLA) and 0.1μg and 1.0μg VEGF. The in vitro VEGF release kinetics was studied using a Sandwich ELISA. The biological activity of the released VEGF was investigated in vitro using human umbilical vein endothelial cells. The potential of the VEGF-releasing suture material was also studied in vivo 5days after implantation in the hind limb of Wistar rats, when the histological findings were analyzed. The essential results, enhanced cell viability in vitro as well as significantly increased vascularization in vivo, were achieved using PLLA/1.0μg VEGF-coated suture material. Furthermore, ELISA measurements revealed a high reproducibility of the VEGF release behavior. Based on the results achieved regarding the dose-effect relationship of VEGF, the stability during its processing and the release behavior, it can be predicted that a bioactive suture material would be successful in later in vivo studies. Therefore, this knowledge could be the basis for future studies, where bioactive substances with different modes of action are combined for targeted, overall enhancement of wound healing. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Floral development and vascularization help to explain merism evolution in Paepalanthus (Eriocaulaceae, Poales

    Directory of Open Access Journals (Sweden)

    Arthur de Lima Silva

    2016-12-01

    Full Text Available Background Flowers in Eriocaulaceae, a monocot family that is highly diversified in Brazil, are generally trimerous, but dimerous flowers occur in Paepalanthus and a few other genera. The floral merism in an evolutionary context, however, is unclear. Paepalanthus encompasses significant morphological variation leading to a still unresolved infrageneric classification. Ontogenetic comparative studies of infrageneric groups in Paepalanthus and in Eriocaulaceae are lacking, albeit necessary to establish evolution of characters such as floral merism and their role as putative synapomorphies. Methods We studied the floral development and vascularization of eight species of Paepalanthus that belong to distinct clades in which dimery occurs, using light and scanning electron microscopies. Results Floral ontogeny in dimerous Paepalanthus shows lateral sepals emerging simultaneously and late-developing petals. The outer whorl of stamens is absent in all flowers examined here. The inner whorl of stamens becomes functional in staminate flowers and is reduced to staminodes in the pistillate ones. In pistillate flowers, vascular bundles reach the staminodes. Ovary vascularization shows ventral bundles in a commissural position reaching the synascidiate portion of the carpels. Three gynoecial patterns are described for the studied species: (1 gynoecium with a short style, two nectariferous branches and two long stigmatic branches, in most species; (2 gynoecium with a long style, two nectariferous branches and two short stigmatic branches, in P. echinoides; and (3 gynoecium with long style, absent nectariferous branches and two short stigmatic branches, in P. scleranthus. Discussion Floral development of the studied species corroborates the hypothesis that the sepals of dimerous flowers of Paepalanthus correspond to the lateral sepals of trimerous flowers. The position and vascularization of floral parts also show that, during dimery evolution in Paepalanthus

  1. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

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    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  2. Effects of Visual Experience on Vascular Endothelial Growth Factor Expression during the Postnatal Development of the Rat Visual Cortex

    Science.gov (United States)

    Argandoña, Enrike G.; Lafuente, José V.

    2008-01-01

    The development of the cortical vascular network depends on functional maturation. External inputs are an essential requirement in the modeling of the visual cortex, mainly during the critical period, when the functional and structural properties of visual cortical neurons are particularly susceptible to alterations. Vascular endothelial growth factor (VEGF) is the major angiogenic factor, a key signal in the induction of vessel growth. Our study focused on the role of visual stimuli on the development of the vascular pattern correlated with VEGF levels. Vascular density and the expression of VEGF were examined in the primary visual cortex of rats reared under different visual environments (dark rearing, dark-rearing in conditions of enriched environment, enriched environment, and laboratory standard conditions) during postnatal development (before, during, and after the critical period). Our results show a restricted VEGF cellular expression to astroglial cells. Quantitative differences appeared during the critical period: higher vascular density and VEGF protein levels were found in the enriched environment group; both dark-reared groups showed lower vascular density and VEGF levels, which means that enriched environment without the physical exercise component does not exert effects in dark-reared rats. PMID:17986606

  3. Therapeutic strategy for lower limb lymphedema and lymphatic fistula after resection of a malignant tumor in the hip joint region: a case report.

    Science.gov (United States)

    Hara, H; Mihara, M; Hayashi, A; Kanemaru, M; Todokoro, T; Yamamoto, T; Iida, T; Hino, R; Koshima, I

    2014-03-01

    Lymphatic fistula complicating lymphedema is thought to occur due to communication between lymph vessels and the skin, which has yet to be shown objectively. The objective of this case report is to show the pathology and treatment using simultaneous lymphatic fistula resection and lymphatico-venous anastomosis (LVA). A 40-year-old woman underwent extended resection and total hip arthroplasty for primitive neuroectodermal tumor in the right proximal femur 23 years ago. Right lower limb lymphedema developed immediately after surgery and lymphatic fistula appeared in the posterior thigh. On ICG lymphography, lymph reflux toward the distal side dispersing in a fan-shape reticular pattern from the lymphatic fistula region was noted after intracutaneous injection of ICG into the foot. We performed simultaneous lymphatic fistula resection and of LVA. Pathological examination showed that the epidermis and stratum corneum of the healthy skin were lost in the lymphatic fistula region. Dilated lymph vessels were open in this region. The examinations provide the first objective evidence that the cause of lymphatic fistula may be lymph reflux from lymphatic stems to precollectors through lymphatic perforators.

  4. Cerebral Lipiodol Embolism after Lymphatic Embolization for Plastic Bronchitis.

    Science.gov (United States)

    Kirschen, Matthew P; Dori, Yoav; Itkin, Maxim; Licht, Daniel J; Ichord, Rebecca; Vossough, Arastoo

    2016-09-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Vascular Cures

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  6. An in situ optical imaging system for measuring lipid uptake, vessel contraction, and lymph flow in small animal lymphatic vessels

    Science.gov (United States)

    Kassis, Timothy; Weiler, Michael J.; Dixon, J. Brandon

    2012-03-01

    All dietary lipids are transported to venous circulation through the lymphatic system, yet the underlying mechanisms that regulate this process remain unclear. Understanding how the lymphatics functionally respond to changes in lipid load is important in the diagnosis and treatment of lipid and lymphatic related diseases such as obesity, hypercholesterolemia, and lymphedema. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. A custom-built optical set-up provides us with the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. This is achieved by dividing the light path into two optical bands. Utilizing high-speed and back-illuminated CCD cameras and post-acquisition image processing algorithms, we have the potential quantify correlations between vessel contraction, lymph flow and lipid concentration of mesenteric lymphatic vessels in situ. Local flow velocity is measured through lymphocyte tracking, vessel contraction through measurements of the vessel walls and lipid uptake through fluorescence intensity tracking of a fluorescent long chain fatty acid analogue, Bodipy FL C16. This system will prove to be an invaluable tool for both scientists studying lymphatic function in health and disease, and those investigating strategies for targeting the lymphatic system with orally delivered drugs.

  7. Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function

    Science.gov (United States)

    Kassis, Timothy; Kohan, Alison B.; Weiler, Michael J.; Nipper, Matthew E.; Cornelius, Rachel; Tso, Patrick; Brandon Dixon, J.

    2012-08-01

    Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C16. This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism.

  8. Development of cell technologies for design of cell contained vascular grafts

    Directory of Open Access Journals (Sweden)

    И. С. Захарова

    2016-01-01

    Full Text Available A new protocol for production of functional endothelial and mural cells from human cardiac explants has been developed. The endothelial cells are characterized by the presence of mature endothelial markers: CD 31, VE-cadherin and VEGFR2. Functionally they could take up ac-LDL, form tube-like structure in matrigel, contains functional cytoplasmic microvesicles Weibel-Palade bodies, in cytoplasm microvesicles – metabolized form of acetylated low-density lipoprotein, form capillary-like structures in Matrigel and produces extracellular matrix. The smooth muscle cells expressed a specific marker aSMA and produces extracellular matrix. The derived cell populations exhibit functional properties in hindlimb ischemia model. It was shown that the endothelial and the smooth muscle cells retain their specific surface antigens and the ability to produce an extracellular matrix on polycaprolactone and polylactide-co-glycolide surfaces. These cells can be used to develop a vascular tissue-graft.

  9. Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma.

    Science.gov (United States)

    Clemente, C G; Boracchi, P; Andreola, S; Del Vecchio, M; Veronesi, P; Rilke, F O

    1992-03-15

    Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients.

  10. Jin Fu Kang Oral Liquid Inhibits Lymphatic Endothelial Cells Formation and Migration

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    Hai-Lang He

    2016-01-01

    Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Jin Fu Kang (JFK, an oral liquid prescription of Chinese herbal drugs, has been clinically available for the treatment of non-small cell lung cancer (NSCLC. Lymphangiogenesis is a primary event in the process of cancer development and metastasis, and the formation and migration of lymphatic endothelial cells (LECs play a key role in the lymphangiogenesis. To assess the activity of stromal cell-derived factor-1 (SDF-1 and the coeffect of SDF-1 and vascular endothelial growth factor-C (VEGF-C on the formation and migration of LECs and clarify the inhibitory effects of JFK on the LECs, the LECs were differentiated from CD34+/VEGFR-3+ endothelial progenitor cells (EPCs, and JFK-containing serums were prepared from rats. SDF-1 and VEGF-C both induced the differentiation of CD34+/VEGFR-3+ EPCs towards LECs and enhanced the LECs migration. Couse of SDF-1 and VEGF-C displayed an additive effect on the LECs formation but not on their migration. JFK inhibited the formation and migration of LECs, and the inhibitory effects were most probably via regulation of the SDF-1/CXCR4 and VEGF-C/VEGFR-3 axes. The current finding suggested that JFK might inhibit NSCLC through antilymphangiogenesis and also provided a potential to discover antilymphangiogenesis agents from natural resources.

  11. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia.

    Science.gov (United States)

    Lukacs, Viktor; Mathur, Jayanti; Mao, Rong; Bayrak-Toydemir, Pinar; Procter, Melinda; Cahalan, Stuart M; Kim, Helen J; Bandell, Michael; Longo, Nicola; Day, Ronald W; Stevenson, David A; Patapoutian, Ardem; Krock, Bryan L

    2015-09-21

    Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we discover a novel role of this channel in the lymphatic system. Through whole-exome sequencing, we identify biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia. Analysis of patients' erythrocytes as well as studies in a heterologous system reveal greatly attenuated PIEZO1 function in affected alleles. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema.

  12. Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis.

    Science.gov (United States)

    Yang, Xiao-Mei; Han, Hai-Xiong; Sui, Fei; Dai, Yu-Min; Chen, Ming; Geng, Jian-Guo

    2010-05-28

    The Slit family of guidance cues binds to Roundabout (Robo) receptors to modulate neuronal, leukocytic, and endothelial migration. Slit-Robo signaling had been reported to function as chemoattractive signal for vascular endothelial cells during angiogenesis. In this study, we found that Robo1 was expressed in lymphatic endothelial cells to mediate the migration and tube formation of these cells upon Slit2 stimulation, which were specifically inhibited by the function-blocking antibody R5 to Slit2/Robo1 interaction. To further explore the lymphangiogenic effect and significance mediated by Slit-Robo signaling, we intercrossed Slit2 transgenic mice with a non-metastatic RIP1-Tag2 mouse tumor model, and found that transgenic overexpression of Slit2 significantly enhanced tumor lymphangiogenesis and subsequently promoted mesenteric lymph node metastasis of pancreatic islet tumors. Taken together, our findings reveal that through interacting with Robo1, Slit2 is a novel and potent lymphangiogenic factor and contributes to tumor lymphatic metastasis.

  13. Ultrasound -- Vascular

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  14. Ultrasound -- Vascular

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate the ... are the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces ...

  15. Modelling Lymphatic Filariasis: Transmission and Control

    NARCIS (Netherlands)

    S. Swaminathan

    2004-01-01

    textabstractLymphatic filariasis (LF) is a mosquito borne parasitic disease of the tropics. Of the three species of parasites causing the disease, W. bancrofti transmitted by Culex quinquefasciatus is the most widely prevalent. Infection can lead to disabling chronic manifestations: lymphoedema, ele

  16. Lymphatic Filariasis: Transmission, Treatment and Elimination

    NARCIS (Netherlands)

    W.A. Stolk (Wilma)

    2005-01-01

    textabstractLymphatic filariasis (LF) is a mosquito-borne, tropical disease caused by filarial worms. Infection can lead to disabling chronic disease, characterized by swelling of extremities or external genitalia (lymphoedema, elephantiasis and hydrocele). Mass treatment with antifilarial drugs is

  17. Lymphatic and venous function in lipoedema.

    Science.gov (United States)

    Harwood, C A; Bull, R H; Evans, J; Mortimer, P S

    1996-01-01

    Lipoedema is a common but infrequently recognized condition causing bilateral enlargement of the legs in women. Although generally considered to be the result of an abnormal deposition of subcutaneous fat with associated oedema, the precise mechanisms responsible for oedema formation have yet to be fully established. In order to evaluate the possible role of lymphatic or venous dysfunction in the pathogenesis of lipoedema, 10 patients were investigated by photoplethysmography (venous function) and quantitative lymphoscintigraphy (lymphatic function). The results were compared with those from patients with primary lymphoedema and those from healthy volunteers. The results demonstrated minor abnormalities of venous function in only two patients. One patient had moderately impaired lymphatic function in both legs and seven patients had a marginal degree of impairment in one or both legs. However, in none of these cases did the impairment attain the low levels seen in true lymphoedema. Lipoedema appears to be a distinct clinical entity best classified as a lipodystrophy rather than a direct consequence of any primary venous or lymphatic insufficiency.

  18. Lymphatic filariasis control in Tanga Region, Tanzania

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Derua, Yahya A.; Magesa, Stephen M.

    2014-01-01

    BackgroundLymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds...

  19. Gelatinases, endonuclease and Vascular Endothelial Growth Factor during development and regression of swine luteal tissue

    Directory of Open Access Journals (Sweden)

    Bacci Maria

    2006-11-01

    Full Text Available Abstract Background The development and regression of corpus luteum (CL is characterized by an intense angiogenesis and angioregression accompanied by luteal tissue and extracellular matrix (ECM remodelling. Vascular Endothelial Growth Factor (VEGF is the main regulator of angiogenesis, promoting endothelial cell mitosis and differentiation. After the formation of neovascular tubes, the remodelling of ECM is essential for the correct development of CL, particularly by the action of specific class of proteolytic enzymes known as matrix metalloproteinases (MMPs. During luteal regression, characterized by an apoptotic process and successively by an intense ECM and luteal degradation, the activation of Ca++/Mg++-dependent endonucleases and MMPs activity are required. The levels of expression and activity of VEGF, MMP-2 and -9, and Ca++/Mg++-dependent endonucleases throughout the oestrous cycle and at pregnancy were analyzed. Results Different patterns of VEGF, MMPs and Ca++/Mg++-dependent endonuclease were observed in swine CL during different luteal phases and at pregnancy. Immediately after ovulation, the highest levels of VEGF mRNA/protein and MMP-9 activity were detected. On days 5–14 after ovulation, VEGF expression and MMP-2 and -9 activities are at basal levels, while Ca++/Mg++-dependent endonuclease levels increased significantly in relation to day 1. Only at luteolysis (day 17, Ca++/Mg++-dependent endonuclease and MMP-2 spontaneous activity increased significantly. At pregnancy, high levels of MMP-9 and VEGF were observed. Conclusion Our findings, obtained from a precisely controlled in vivo model of CL development and regression, allow us to determine relationships among VEGF, MMPs and endonucleases during angiogenesis and angioregression. Thus, CL provides a very interesting model for studying factors involved in vascular remodelling.

  20. Oral vascular malformations: laser treatment and management

    Science.gov (United States)

    Romeo, U.; Rocchetti, F.; Gaimari, G.; Tenore, G.; Palaia, G.; Lo Giudice, G.

    2016-03-01

    Vascular malformations are a very heterogeneous group of circulatory system's diseases that can involve different kind of vessels: arterial, venous or lymphatic ones. Many treatments, such as conventional surgery, embolization, steroid therapy and laser therapy, are available for vascular lesions. The laser approach relies more therapeutic techniques: the transmucosal thermophotocoagulation, intralesional photocoagulation, the excisional biopsy. Today laser is demonstrated to be the gold standard technique to treat vascular lesions that allows a safe and efficient treatment and a lower post-operative healing time. The only disadvantage is the risk of carbonization that could be avoided by using the multiple-spot single pulsed wave technique.

  1. Lymphoscintigraphy patterns in newborns and children with congenital lymphatic dysplasia.

    Science.gov (United States)

    Bellini, C; Villa, G; Sambuceti, G; Traggiai, C; Campisi, C; Bellini, T; Morcaldi, G; Massocco, D; Bonioli, E; Boccardo, F

    2014-03-01

    We performed lymphoscintigraphy on 31 patients (newborns and children) affected by congenital lymphatic dysplasia according to our previously published protocol. Congenital lymphatic dysplasia may present with various degrees of clinical severity, ranging from nonimmune hydrops fetalis with visceral effusions to lymphedema alone. We recommend that lymphoscintigraphy should be strongly considered in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, in order to obtain a very early diagnosis and to start treatment. Lymphoscintigraphy is safe and useful in the diagnosis of lymphatic dysplasia in the newborn and children. Moreover, it is well tolerated by patients and well accepted by their parents.

  2. Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia

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    K.S. Schwab

    2016-06-01

    Full Text Available Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.

  3. Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia.

    Science.gov (United States)

    Schwab, K S; Heine, A; Weimann, T; Kristiansen, G; Brossart, P

    2016-01-01

    Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.

  4. Development and Validation of a Preprocedural Risk Score to Predict Access Site Complications After Peripheral Vascular Interventions Based on the Vascular Quality Initiative Database

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    Daniel Ortiz

    2016-01-01

    Full Text Available Purpose: Access site complications following peripheral vascular intervention (PVI are associated with prolonged hospitalization and increased mortality. Prediction of access site complication risk may optimize PVI care; however, there is no tool designed for this. We aimed to create a clinical scoring tool to stratify patients according to their risk of developing access site complications after PVI. Methods: The Society for Vascular Surgery’s Vascular Quality Initiative database yielded 27,997 patients who had undergone PVI at 131 North American centers. Clinically and statistically significant preprocedural risk factors associated with in-hospital, post-PVI access site complications were included in a multivariate logistic regression model, with access site complications as the outcome variable. A predictive model was developed with a random sample of 19,683 (70% PVI procedures and validated in 8,314 (30%. Results: Access site complications occurred in 939 (3.4% patients. The risk tool predictors are female gender, age > 70 years, white race, bedridden ambulatory status, insulin-treated diabetes mellitus, prior minor amputation, procedural indication of claudication, and nonfemoral arterial access site (model c-statistic = 0.638. Of these predictors, insulin-treated diabetes mellitus and prior minor amputation were protective of access site complications. The discriminatory power of the risk model was confirmed by the validation dataset (c-statistic = 0.6139. Higher risk scores correlated with increased frequency of access site complications: 1.9% for low risk, 3.4% for moderate risk and 5.1% for high risk. Conclusions: The proposed clinical risk score based on eight preprocedural characteristics is a tool to stratify patients at risk for post-PVI access site complications. The risk score may assist physicians in identifying patients at risk for access site complications and selection of patients who may benefit from bleeding avoidance

  5. Maximum shortening velocity of lymphatic muscle approaches that of striated muscle.

    Science.gov (United States)

    Zhang, Rongzhen; Taucer, Anne I; Gashev, Anatoliy A; Muthuchamy, Mariappan; Zawieja, David C; Davis, Michael J

    2013-11-15

    Lymphatic muscle (LM) is widely considered to be a type of vascular smooth muscle, even though LM cells uniquely express contractile proteins from both smooth muscle and cardiac muscle. We tested the hypothesis that LM exhibits an unloaded maximum shortening velocity (Vmax) intermediate between that of smooth muscle and cardiac muscle. Single lymphatic vessels were dissected from the rat mesentery, mounted in a servo-controlled wire myograph, and subjected to isotonic quick release protocols during spontaneous or agonist-evoked contractions. After maximal activation, isotonic quick releases were performed at both the peak and plateau phases of contraction. Vmax was 0.48 ± 0.04 lengths (L)/s at the peak: 2.3 times higher than that of mesenteric arteries and 11.4 times higher than mesenteric veins. In cannulated, pressurized lymphatic vessels, shortening velocity was determined from the maximal rate of constriction [rate of change in internal diameter (-dD/dt)] during spontaneous contractions at optimal preload and minimal afterload; peak -dD/dt exceeded that obtained during any of the isotonic quick release protocols (2.14 ± 0.30 L/s). Peak -dD/dt declined with pressure elevation or activation using substance P. Thus, isotonic methods yielded Vmax values for LM in the mid to high end (0.48 L/s) of those the recorded for phasic smooth muscle (0.05-0.5 L/s), whereas isobaric measurements yielded values (>2.0 L/s) that overlapped the midrange of values for cardiac muscle (0.6-3.3 L/s). Our results challenge the dogma that LM is classical vascular smooth muscle, and its unusually high Vmax is consistent with the expression of cardiac muscle contractile proteins in the lymphatic vessel wall.

  6. Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm

    DEFF Research Database (Denmark)

    Waeckel, L.; Badier-Commander, C.; Damery, T.

    2015-01-01

    Angiotensin-II and oxidative stress are involved in the genesis of aortic aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS) deletion or uncoupling. The purpose of this work was to study the endothelial function in wild-type C57BL/6 (BL) and transgenic mice expressing...... not affected in BLSL and AR. However, in ARSL, endothelium-dependent relaxations (acetylcholine, UK-14304) were significantly reduced, and this dysfunction was similar in aortae without or with aneurysms. The endothelial impairment was unaffected by catalase, superoxide-dismutase mimetic, radical scavengers......, cyclooxygenase inhibition, or TP-receptor blockade and could not be attributed to sGC oxidation. Thus, ARSL is a severe hypertension model developing aortic aneurysm. A vascular dysfunction, involving both endothelial (reduced role of NO) and smooth muscle cells, precedes aneurysms formation and, paradoxically...

  7. 5'-Ectonucleotidase/CD73 expression on lymph-circulating lymphocytes and lymphatic endothelial cells offers new paths to explore barrier function.

    Science.gov (United States)

    Sidibé, Adama; Imhof, Beat A

    2015-02-01

    5'-Nucleotidase/CD73 is a key enzyme in the regulation of purinergic signaling, hydrolyzing extracellular AMP to produce adenosine, which is critical in the blood vascular system and in immunosuppression. CD73 is expressed by both blood endothelial cells and lymphatic endothelial cells. Although the role of CD73 on blood endothelial cells in controlling vascular permeability and leukocyte trafficking has been studied, the role of lymphatic CD73 has thus far remained unknown. In this issue of European Journal of Immunology, Yegutkin et al. [Eur. J. Immunol. 2015. 45: 562-573] compare CD73 activity in the endothelia of lymphatics and blood vessels and investigate the CD73(+) lymphocyte subpopulations possibly involved in immunoregulation. This Commentary will discuss how the authors' work sheds light on the differential use of CD73 by these two cell populations to control endothelial permeability and sprouting.

  8. CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability.

    Science.gov (United States)

    Ivanov, Stoyan; Scallan, Joshua P; Kim, Ki-Wook; Werth, Kathrin; Johnson, Michael W; Saunders, Brian T; Wang, Peter L; Kuan, Emma L; Straub, Adam C; Ouhachi, Melissa; Weinstein, Erica G; Williams, Jesse W; Briseño, Carlos; Colonna, Marco; Isakson, Brant E; Gautier, Emmanuel L; Förster, Reinhold; Davis, Michael J; Zinselmeyer, Bernd H; Randolph, Gwendalyn J

    2016-04-01

    Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7-/- mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4-positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs.

  9. Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density

    Directory of Open Access Journals (Sweden)

    Metcalfe Chris

    2010-05-01

    Full Text Available Abstract Background Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB, which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group. Methods Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators. Results The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis was also effective when combined into the Shields index in a cohort of 24 patients. Conclusions These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.

  10. Thymosin β4 Improves Differentiation and Vascularization of EHTs

    Science.gov (United States)

    Ziegler, Tilman; Hinkel, Rabea; Stöhr, Andrea; Eschenhagen, Thomas; Laugwitz, Karl-Ludwig; le Noble, Ferdinand; David, Robert; Hansen, Arne

    2017-01-01

    Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation. We examined the potential impact of Tβ4 to enhance maturation of cardiomyocytes from iPSCs. Assessing the expression of transcription factors associated with cardiac differentiation, we were able to demonstrate the increased generation of cells displaying cardiomyocyte characteristics in vitro. Furthermore, we demonstrated, in a zebrafish model of embryonic vascular development, that Tβ4 is crucial for the proper execution of lymphatic and angiogenic vessel sprouting. Finally, utilizing Tβ4-transduced EHTs generated from mice genetically engineered to label endothelial cells in vitro, we show that treatment with Tβ4 promotes vascularization and contractility in EHTs, highlighting Tβ4 as a growth factor improving the formation of cardiomyocytes from iPSC and enhancing the performance of EHTs generated from neonatal cardiomyocytes. PMID:28191018

  11. Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report

    OpenAIRE

    El Husseiny Noha M; Mattar Mervat M

    2011-01-01

    Abstract Introduction Vasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time. Case presentation We report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutane...

  12. Pattern of lymph node metastases of squamous cell esophageal cancer based on the anatomical lymphatic drainage system: efficacy of lymph node dissection according to tumor location

    Science.gov (United States)

    2017-01-01

    Knowing the anatomical lymphatic drainage of the esophagus is crucial to understanding the dissemination pattern of esophageal tumor. During the embryonal growth, the middle and lower part of the esophagus stretches as the lymphatic networks develop in the submucosal layer. The abundant submucosal lymphatics drain in a longitudinal fashion directly to their proximal and distal ends. The lymphatic route from the proximal esophagus through recurrent nerve nodes to supraclavicular nodes are a component of the mesentery of the proximal esophagus. The lower esophagus mostly drains its lymph into paracardial nodes related to celiac nodes through the mesentery of the distal esophagus. Lymphatic routes to mid and lower paraesophageal nodes usually originate from the intermuscular area of the muscularis propria. The lymphatic communication between the submucosa and intermuscular area is limited. The anatomical concept was confirmed clinically by a large series of single institution and the nationwide registry in Japan. The clinical data for the incidence of involved nodes verified the anatomical observations that long longitudinal extension of lymphatic drainage in the submucosa connected to the upper mediastinum lymphatics and paracardial lymphatics. The extent of dissection should be not tailored according to the anatomical distance from the tumor but according to the incidences of metastasis of each area, those were differed by tumor location. The areas for node dissection should be modified according to the tumor location. Although in patients with tumor limited to within the submucosal layer, even with tumors located in the mid- and lower esophagus, lymphatic metastasis was frequent in the upper mediastinum and perigastric area via the abundant submucosal lymphatics in a longitudinal fashion. When tumor invades or penetrates the muscle layer, the incidence of paraesophageal lymph node metastasis in the middle and lower mediastinum increases. PMID:28815068

  13. The Notch Ligand Delta-Like 4 Regulates Multiple Stages of Early Hemato-Vascular Development

    Science.gov (United States)

    Neves, Hélia; Gomes, Andreia C.; Saavedra, Pedro; Carvalho, Catarina C.; Duarte, António; Cidadão, António; Parreira, Leonor

    2012-01-01

    Background In mouse embryos, homozygous or heterozygous deletions of the gene encoding the Notch ligand Dll4 result in early embryonic death due to major defects in endothelial remodeling in the yolk sac and embryo. Considering the close developmental relationship between endothelial and hematopoietic cell lineages, which share a common mesoderm-derived precursor, the hemangioblast, and many key regulatory molecules, we investigated whether Dll4 is also involved in the regulation of early embryonic hematopoiesis. Methodology/Principal Findings Using Embryoid Bodies (EBs) derived from embryonic stem cells harboring hetero- or homozygous Dll4 deletions, we observed that EBs from both genotypes exhibit an abnormal endothelial remodeling in the vascular sprouts that arise late during EB differentiation, indicating that this in vitro system recapitulates the angiogenic phenotype of Dll4 mutant embryos. However, analysis of EB development at early time points revealed that the absence of Dll4 delays the emergence of mesoderm and severely reduces the number of blast-colony forming cells (BL-CFCs), the in vitro counterpart of the hemangioblast, and of endothelial cells. Analysis of colony forming units (CFU) in EBs and yolk sacs from Dll4+/− and Dll4−/− embryos, showed that primitive erythropoiesis is specifically affected by Dll4 insufficiency. In Dll4 mutant EBs, smooth muscle cells (SMCs) were seemingly unaffected and cardiomyocyte differentiation was increased, indicating that SMC specification is Dll4-independent while a normal dose of this Notch ligand is essential for the quantitative regulation of cardiomyogenesis. Conclusions/Significance This study highlights a previously unnoticed role for Dll4 in the quantitative regulation of early hemato-vascular precursors, further indicating that it is also involved on the timely emergence of mesoderm in early embryogenesis. PMID:22514637

  14. Immunocytochemical localization of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 of the human deciduous molar tooth germ development in the human fetus.

    Science.gov (United States)

    Miwa, Yoko; Fujita, Toshiya; Sunohara, Masataka; Sato, Iwao

    2008-01-01

    Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel endothelial development. We used immunohistochemical methods to demonstrate the localization of VEGF and its receptors, showing the specific expression pattern of VEGF and VEGF receptor in the human deciduous tooth from the cap to late bell stages in the human fetus. Immunoreactivity to VEGF and its receptor VEGF receptor-2 (VEGFR-2) was intensely positive in the inner enamel epithelium at the cap stage and ranged from negative to moderately positive in the bell stage. At the late bell stage, VEGF immunoreactivity was mainly positive but weak for VEGFR-2. The intensity of VEGF and VEGFR-2 in odontoblasts increases from cap stage to late bell stage. We postulate that the dissimilar expression of VEGF in inner enamel epithelium, ameloblast and odontoblast during each stage of human tooth development may affect tooth germ formation.

  15. Process development for high-resolution 3D-printing of bioresorbable vascular stents

    Science.gov (United States)

    Ware, Henry Oliver T.; Farsheed, Adam C.; van Lith, Robert; Baker, Evan; Ameer, Guillermo; Sun, Cheng

    2017-02-01

    The recent development of "continuous projection microstereolithography" also known as CLIP technology has successfully alleviated the main obstacles surrounding 3D printing technologies: production speed and part quality. Following the same working principle, we further developed the μCLIP process to address the needs for high-resolution 3D printing of biomedical devices with micron-scale precision. Compared to standard stereolithography (SLA) process, μCLIP fabrication can reduce fabrication time from several hours to as little as a few minutes. μCLIP can also produce better surface finish and more uniform mechanical properties than conventional SLA, as each individual "fabrication layer" continuously polymerizes into the subsequent layer. In this study, we report the process development in manufacturing high-resolution bioresorbable stents using our own μCLIP system. The bioresorbable photopolymerizable biomaterial (B-ink) used in this study is methacrylated poly(1, 12 dodecamethylene citrate) (mPDC). Through optimization of our μCLIP process and concentration of B-ink components, we have created a customizable bioresorbable stent with similar mechanical properties exhibited by nitinol stents. Upon optimization, fabricating a 2 cm tall vascular stent that comprises 4000 layers was accomplished in 26.5 minutes.

  16. Effects of heavy ion radiation on the brain vascular system and embryonic development

    Science.gov (United States)

    Yang, T. C.; Tobias, C. A.

    Using neonatal rats as a model system, we investigated the response of the brain vascular system to ionizing radiation and found that distinct petechial hemorrages developed in the cerebral cortex within a few hours after irradiation, reached a maximum about 13 to 24 hours, and decreased exponentially with time. No brain hemorrhage was found in neonatal rats 12 days after irradiation. Our experimental results indicate that a dose of a few hundred rad of X rays can induce a significant number of hemorrhages in the brain, and the number of lesions increases exponentially with dose. Heavy ions induce more hemorrhages than X rays for a given dose, and the RBE for 670 MeV/u neon particles ranges from about 2.0 for low doses to about 1.4 for high doses. A histological study on the hemorrhages indicates that a large number of red blood cells leak from the blood vessels. The radiation-induced hemorrhages may be a result of some capillary membrane damages or reproductive death of some blood vessel epithelial cells. The fast onset of hemorrhage after irradiation suggests that some membrane damage may be involved. The effect of heavy-ion radiation on the embryonic development was studied with energetic iron particles. Pregnant mice were whole-body irradiated with 600 MeV/u iron particles on day 6 of gestation and were sacrificed 12 days after irradiation. Various physical abnormalities were observed, and embryos irradiated with 1 rad iron particles showed retardation of body development.

  17. Flowers regulate the growth and vascular development of the inflorescence rachis in Vitis vinifera L.

    Science.gov (United States)

    Gourieroux, Aude M; McCully, Margaret E; Holzapfel, Bruno P; Scollary, Geoffrey R; Rogiers, Suzy Y

    2016-11-01

    The rachis, the structural framework of the grapevine (Vitis vinifera L.) inflorescence (and subsequent bunch), consists of a main axis and one or more orders of lateral branches with the flower-bearing pedicels at their fine tips. The rachis is crucial both for support, and transport from the shoot. Earlier suggestions that the flowers per se affect normal rachis development are investigated further in this study. Different percentages (0, 25, 50, 75 or 100) of flowers were removed manually one week before anthesis on field-grown vines. Treatment effects on subsequent rachis development (curvature, vitality, anatomy, starch deposit) were assessed. Sections, both fixed and embedded, and fresh hand-cut were observed by fluorescence and bright-field optics after appropriate staining. Emphasis was on measurement of changes in cross-sectional area of secondary xylem and phloem, and on maturation of fibres and periderm. Specific defects in rachis development were dependent on the percent and location of flower removal one week prior to anthesis. The rachises curved inwards where most of the flowers were removed. When fully de-flowered, they became progressively necrotic from the laterals back to the primary axes and from the distal to the proximal end of those axes, with a concurrent disorganisation of their anatomy. A few remaining groups of flowers prevented desiccation and abscission of the rachis axes proximal to the group, but not distally. Flower removal (50%) reduced rachis elongation, while 75% removal reduced xylem and phloem area and delayed phloem fibre and periderm development. 75% flower removal did not affect starch present in the rachis during berry development. Developing flowers affect the growth and vitality of the rachis and the development of its vascular and support structures. The extent of these effects depends on the cultivar and the number and position of flowers remaining after some are removed one week before anthesis. Copyright © 2016

  18. Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 regulates xylem development and growth by a conserved mechanism that modulates hormone signaling.

    Science.gov (United States)

    Grienenberger, Etienne; Douglas, Carl J

    2014-04-01

    Despite a strict conservation of the vascular tissues in vascular plants (tracheophytes), our understanding of the genetic basis underlying the differentiation of secondary cell wall-containing cells in the xylem of tracheophytes is still far from complete. Using coexpression analysis and phylogenetic conservation across sequenced tracheophyte genomes, we identified a number of Arabidopsis (Arabidopsis thaliana) genes of unknown function whose expression is correlated with secondary cell wall deposition. Among these, the Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 (VUP1) gene encodes a predicted protein of 24 kD with no annotated functional domains but containing domains that are highly conserved in tracheophytes. Here, we show that the VUP1 expression pattern, determined by promoter-β-glucuronidase reporter gene expression, is associated with vascular tissues, while vup1 loss-of-function mutants exhibit collapsed morphology of xylem vessel cells. Constitutive overexpression of VUP1 caused dramatic and pleiotropic developmental defects, including severe dwarfism, dark green leaves, reduced apical dominance, and altered photomorphogenesis, resembling brassinosteroid-deficient mutants. Constitutive overexpression of VUP homologs from multiple tracheophyte species induced similar defects. Whole-genome transcriptome analysis revealed that overexpression of VUP1 represses the expression of many brassinosteroid- and auxin-responsive genes. Additionally, deletion constructs and site-directed mutagenesis were used to identify critical domains and amino acids required for VUP1 function. Altogether, our data suggest a conserved role for VUP1 in regulating secondary wall formation during vascular development by tissue- or cell-specific modulation of hormone signaling pathways.

  19. The plant-specific Dof transcription factors family: new players involved in vascular system development and functioning in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Rozenn eLe Hir

    2013-05-01

    Full Text Available In higher plants phloem and xylem are responsible for long-distance transport of water, nutrients, and signals that act systemically at short or long distance to coordinate developmental processes. The formation of the plant vascular system is a complex process that integrates signalling events and gene regulation at transcriptional and posttranscriptional levels. Thanks to transcriptomic and proteomic analysis we start to better understand the mechanisms underlying the formation and the functioning of the vascular system. The role of the DNA-binding with one finger (Dof TFs, a group of plant–specific transcription factors, recently emerged as part of the transcriptional regulatory networks acting on the formation and functioning of the vascular tissues. More than half of the members of this TF family are expressed in the vascular system. In addition some of them have been proposed to be mobile proteins, suggesting a possible role in the control of short- or long-distance signalling as well. This review summarizes the current knowledge on Dof TFs family in Arabidopsis with a special focus on their role in vascular development and functioning.

  20. Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development.

    Science.gov (United States)

    Mastrangelo, F; Sberna, M T; Tettamanti, L; Cantatore, G; Tagliabue, A; Gherlone, E

    2016-01-01

    Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis.

  1. Metabolic syndrome and the development of vascular disease and type 2 diabetes in high-risk patients

    NARCIS (Netherlands)

    Wassink, A.M.J.

    2009-01-01

    Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and

  2. Metabolic syndrome and the development of vascular disease and type 2 diabetes in high-risk patients

    NARCIS (Netherlands)

    Wassink, A.M.J.

    2009-01-01

    Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and atherosc

  3. Tailoring of chronic lymphatic leukemia therapy

    OpenAIRE

    Elhefni, Ashraf M

    2013-01-01

    Chronic lymphocytic leukemia (CLL) remains an incurable disease, with all patients who require therapy destined to relapse and understanding of the pathophysiology of chronic lymphocytic leukemia has advanced significantly. It is now clear that chronic lymphocytic leukemia is a relatively proliferative disorder that requires the help of its microenvironment to be maintained and to progress. The stimulation of the chronic lymphatic leukemia cell occurs in most, if not all, patients through ant...

  4. Influence of Environmental Changes on Physiology and Development of Polar Vascular Plants

    Science.gov (United States)

    Giełwanowska, Irena; Pastorczyk, Marta; Kellmann-Sopyła, Wioleta

    2011-01-01

    Polar vascular plants native to the Arctic and the Antarctic geobotanical zone have been growing and reproducing effectively under difficult environmental conditions, colonizing frozen ground areas formerly covered by ice. Our macroscopic observations and microscopic studies conducted by means of a light microscope (LM) and transmission electron microscope (TEM) concerning the anatomical and ultrastructural observations of vegetative and generative tissue in Cerastium arcticum, Colobanthus quitensis, Silene involucrata, plants from Caryophyllaceae and Deschampsia antarctica, Poa annua and Poa arctica, from Poaceae family. In the studies, special attention was paid to plants coming from diversity habitats where stress factors operated with clearly different intensity. In all examinations plants, differences in anatomy were considerable. In Deschampsia antarctica the adaxial epidermis of hairgrass leaves from a humid microhabitat, bulliform cells differentiated. Mesophyll was composed of cells of irregular shapes and resembled aerenchyma. The ultrastructural observations of mesophyll in all plants showed tight adherence of chloroplasts, mitochondria and peroxisomes, surface deformations of these organelles and formation of characteristic outgrowths and pocket concavities filled with cytoplasm with vesicles and organelles by chloroplasts. In reproduction biology of examined Caryophyllaceae and Poaceae plants growing in natural conditions, in the Arctic and in the Antarctic, and in a greenhouse in Olsztyn showed that this plant develops two types of bisexual flowers. Almost all ovules developed and formed seeds with a completely differentiated embryo both under natural conditions in the Arctic and the Antarctic and in a greenhouse in Olsztyn.

  5. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance.

    Science.gov (United States)

    Bagchi, Mandrita; Kim, Leo A; Boucher, Jeremie; Walshe, Tony E; Kahn, C Ronald; D'Amore, Patricia A

    2013-08-01

    Vascular endothelial growth factor (VEGF) is critical for angiogenesis, but also has pleiotropic effects on several nonvascular cells. Our aim was to investigate the role of VEGF in brown adipose tissue (BAT). We show that VEGF expression increases 2.5-fold during differentiation of cultured murine brown adipocytes and that VEGF receptor-2 is phosphorylated, indicating VEGF signaling. VEGF increased proliferation in brown preadipocytes in vitro by 70%, and blockade of VEGF signaling using anti-VEGFR2 antibody DC101 increased brown adipocyte apoptosis, as determined by cell number and activation of caspase 3. Systemic VEGF neutralization in mice, accomplished by adenoviral expression of soluble Flt1, resulted in 7-fold increase in brown adipocyte apoptosis, mitochondrial degeneration, and increased mitophagy compared to control mice expressing a null adenovirus. Absence of the heparan sulfate-binding VEGF isoforms, VEGF164 and VEGF188, resulted in abnormal BAT development in mice at E15.5, with fewer brown adipocytes and lower mitochondrial protein compared to wild-type littermates. These results suggest a role for VEGF in brown adipocytes and preadipocytes to promote survival, proliferation, and normal mitochondria and development.

  6. Molecular Signature for Lymphatic Invasion Associated with Survival of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Paik, E Sun; Choi, Hyun Jin; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Choi, Chel Hun

    2017-05-22

    We aimed to develop molecular classifier that can predict lymphatic invasion and their clinical significance in epithelial ovarian cancer (EOC) patients. We analyzed gene expression (mRNA, methylated DNA) in data from The Cancer Genome Atlas. To identify molecular signatures for lymphatic invasion, we found differentially expressed genes. The performance of classifier was validated by receiver operating characteristics analysis, logistic regression, linear discriminant analysis (LDA), and support vector machine (SVM). We assessed prognostic role of classifier using random survival forest (RSF) model and pathway deregulation score (PDS). For external validation, we analyzed microarray data from 26 EOC samples of Samsung Medical Center and curatedOvarianData database. We identified 21 mRNAs, and 7 methylated DNAs from primary EOC tissues that predicted lymphatic invasion, and created prognostic models. The classifier predicted lymphatic invasion well, which was validated by logistic regression, LDA, and SVM algorithm (C-index of 0.90, 0.71, and 0.74 for mRNA and C-index of 0.64, 0.68, and 0.69 for DNA methylation). Using RSF model, incorporating molecular data with clinical variables improved prediction of progression-free survival compared with using only clinical variables (P < 0.001 and P = 0.008). Similarly, PDS enabled us to classify patients into high-risk and low-risk group, which resulted in survival difference in mRNA profiles (Log rank P value = 0.011). In external validation, gene signature was well correlated with prediction of lymphatic invasion and patients' survival. Molecular signature model predicting lymphatic invasion was well performed, and also associated with survival of EOC patients.

  7. Vascular endothelial growth factor behavior in different stages of tooth germ development.

    Science.gov (United States)

    Mastrangelo, Filiberto; Sberna, Maria T; Vinci, Raffaele; Iaderosa, Giovanni; Tettamanti, Lucia; Cantatore, Giuseppe; Tagliabue, Angelo; Gherlone, Enrico F

    2016-08-01

    Scientific studies show a possible influence of intercellular and intracellular proteins (VEGF) on the development of physiological and pathological tissue. VEGF, a key regulator of angiogenesis, it would seem essential to take action during the embryonic development of the dental germ. The purpose of the study is to investigate the importance of the enzymatic activity of VEGF through protein quantification at different stages of tooth germ development. The quantification of VEGF protein was performed by 3 different laboratory tests: Western-blot analysis, semi-quantitative reverse transcriptase-polymerase chain reaction analysis (RT-PCR) and finally immunohistochemical analysis. Cell cultures of tooth tissue examined are: endothelial cells, stellate reticulum cells, odontoblasts and ameoblast. The VEGF peptide seems to induce an intense cell proliferation, not concomitant with differentiation towards the endothelial line. The expression of VEGF in the inner enamel epithelium (ameloblasts) would seem to depend on the stage of differentiation, leading us to deduce that VEGF and its respective receptor are expressed in dental germ and that induce alterations not only on the vascularization, but also on the inner epithelium activation and then on dental enamel development, respectively on cap and bell stages of embryogenesis. In our survey, the positive expression of VEGF in all the samples examined, might suggest a fundamental role of angiogenic gene proteins during all stages of embryonic tooth development. It is also characteristic the behavior of stellate reticulum cells, with a significant reduction in VEGF action between early and late stage, which could suggest a possible role of stellate reticulum cells, which would be able to promote and maintain an adequate energy supply to the tissues during early and late stages of differentiation and proliferation.

  8. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells.

    Science.gov (United States)

    Hutton, Daphne L; Moore, Erika M; Gimble, Jeffrey M; Grayson, Warren L

    2013-09-01

    Vasculature is essential to the functional integration of a tissue-engineered bone graft to enable sufficient nutrient delivery and viability after implantation. Native bone and vasculature develop through intimately coupled, tightly regulated spatiotemporal cell-cell signaling. The complexity of these developmental processes has been a challenge for tissue engineers to recapitulate, resulting in poor codevelopment of both bone and vasculature within a unified graft. To address this, we cultured adipose-derived stromal/stem cells (ASCs), a clinically relevant, single cell source that has been previously investigated for its ability to give rise to vascularized bone grafts, and studied the effects of initial spatial organization of cells, the temporal addition of growth factors, and the presence of exogenous platelet-derived growth factor-BB (PDGF-BB) on the codevelopment of bone and vascular tissue structures. Human ASCs were aggregated into multicellular spheroids via the hanging drop method before encapsulation and subsequent outgrowth in fibrin gels. Cellular aggregation substantially increased vascular network density, interconnectivity, and pericyte coverage compared to monodispersed cultures. To form robust vessel networks, it was essential to culture ASCs in a purely vasculogenic medium for at least 8 days before the addition of osteogenic cues. Physiologically relevant concentrations of exogenous PDGF-BB (20 ng/mL) substantially enhanced both vascular network stability and osteogenic differentiation. Comparisons with the bone morphogenetic protein-2, another pro-osteogenic and proangiogenic growth factor, indicated that this potential to couple the formation of both lineages might be unique to PDGF-BB. Furthermore, the resulting tissue structure demonstrated the close association of mineral deposits with pre-existing vascular structures that have been described for developing tissues. This combination of a single cell source with a potent induction factor

  9. Lymphatic Filariasis Disseminating to the Upper Extremity

    Directory of Open Access Journals (Sweden)

    Catherine Maldjian

    2014-01-01

    Full Text Available Lymphatic filariasis is the most common cause of acquired lymphedema worldwide (Szuba and Rockson, 1998. It is endemic to tropical and subtropical regions, and its effects are devastating. With over 100 million infected persons, it ranks second only to leprosy as the leading cause of permanent and long-term disability. Wuchereria bancrofti is the etiologic agent in 90% of cases. There is a dearth of published MRI findings with pathologically proven active infections, making this entity even more of a diagnostic dilemma. Imaging may provide the first clue that one is dealing with a parasite and may facilitate proper treatment and containment of this disease. This is the first report of pathologic correlation with MRI findings in the extremity in active filariasis. The magnetic resonance images demonstrate an enhancing, infiltrative, mass-like appearance with partial encasement of vasculature that has not been previously described in filariasis. Low signal strands in T2-hyperintense dilated lymphatic channels are seen and may depict live adult worms. We hypothesize that the low signal strands correspond to the collagen rich acellular cuticle. This, in combination with the surrounding hyperintense T2 signal, corresponding to a dilated lymphatic channel, may provide more specific MRI findings for active nematodal infection, which can prompt early biopsy, pathological correlation, and diagnosis.

  10. Bioactive coating with low-fouling polymers for the development of biocompatible vascular implants

    Science.gov (United States)

    Thalla, Pradeep Kumar

    The replacement of occluded blood vessels and endovascular aneurysm repair (EVAR) are performed with the use of synthetic vascular grafts and stent grafts, respectively. Both implants lead to frequent clinical complications that are different but due to a similar problem, namely the inadequate surface properties of the polymeric biomaterials used (generally polyethylene terephthalate (PET) or expanded polytetrafluoroethylene (ePTFE)). Therefore the general objective of this thesis was to create a versatile bioactive coating on vascular biomaterials that reduce material-induced thrombosis and promote desired cell interactions favorable to tissue healing around implants. The use of low-fouling backgrounds was decided in order to reduce platelet adhesion as well as the non-specific protein adsorption and thus increase the bioactivity of immobilized biomolecules. As part of the preliminary objective, a multi-arm polyethylene glycol (PEG) was chosen to create a versatile low-fouling surface, since the current coating methods are far from being versatile and rely on the availability of compatible functional groups on both PEG and the host surface. This PEG coating method was developed by taking advantage of novel primary amine-rich plasma polymerized coatings (LP). As demonstrated by quartz crystal microbalance with dissipation (QCM-D), fluorescence measurements and platelet adhesion assays, our PEG coatings exhibited low protein adsorption and almost no platelet adhesion after 15 min perfusion in whole blood. Although protein adsorption was not completely abrogated and short-term platelet adhesion assay was clearly insufficient to draw conclusions for long-term prevention of thrombosis in vivo, the low-fouling properties of this PEG coating were sufficient to be exploited for further coupling of bioactive molecules to create bioactive coatings. Therefore, as a part of the second objective, an innovative and versatile bioactive coating was developed on PEG and

  11. Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    FusunOzmen; MahirOzmen; EvrenOzdemir; MunevverMoran; SeldaSeckin; DicleGUC; ErgunKaraagaoglu; EminKansu

    2011-01-01

    AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their levels and clinicopathological parameters in gastric cancer.METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

  12. Live imaging of newly formed lymphatic vessels in the cornea

    Institute of Scientific and Technical Information of China (English)

    Don Yuen; Xiufeng Wu; Alex C Kwan; Jeffrey LeDue; Hui Zhang; Tatiana Ecoiffier; Bronislaw Pytowski; Lu Chen

    2011-01-01

    Dear Editor,Lymphatic research denotes a field of new discovery and has experienced exponential growth in recent years [1-3].Though lymphatic dysfunction has been found in a broad spectrum of disorders from transplant rejection to cancer metastasis,to date,there is still little effective treatment for lymphatic diseases,so it is a field with urgent demand for new experimental approaches and therapeutic protocols.The cornea provides an ideal site for lymphatic research due to its accessible location,transparent nature,and alymphatic status under normal condition [2,4].Indeed,the use of this tissue for tumor angiogenesis research dates back to 1970s [5].Most recently,we have demonstrated that the cornea possesses a full range of plasticity in lymphatic formation and regression [6].An advanced technology for live imaging of lymphatic vessels in this tissue would therefore have widespread applications in biomedical research.

  13. Large-scale proteome comparative analysis of developing rhizomes of the ancient vascular plant Equisetum hyemale.

    Directory of Open Access Journals (Sweden)

    Tiago Santana Balbuena

    2012-06-01

    Full Text Available Equisetum hyemale is a widespread vascular plant species, whose reproduction is mainly dependent on the growth and development of the rhizomes. Due to its key evolutionary position, the identification of factors that could be involved in the existence of the rhizomatous trait may contribute to a better understanding of the role of this underground organ for the successful propagation of this and other plant species. In the present work, we characterized the proteome of E. hyemale rhizomes using a GeLC-MS spectral-counting proteomics strategy. A total of 1,911 and 1,860 non-redundant proteins were identified in the rhizomes apical tip and elongation zone, respectively. Rhizome- characteristic proteins were determined by comparisons of the developing rhizome tissues to developing roots. A total of 87 proteins were found to be up-regulated in both E. hyemale rhizome tissues in relation to developing roots. Hierarchical clustering indicated a vast dynamic range in the expression of the 87 characteristic proteins and revealed, based on the expression profile, the existence of 9 major protein groups. Gene ontology analyses suggested an over-representation of the terms involved in macromolecular and protein biosynthetic processes, gene expression and nucleotide and protein binding functions. Spatial differences analysis between the rhizome apical tip and the elongation zone revealed that only eight proteins were up-regulated in the apical tip including RNA-binding proteins and an acyl carrier protein, as well as a KH-domain protein and a T-complex subunit; while only seven proteins were up-regulated in the elongation zone including phosphomannomutase, galactomannan galactosyltransferase, endoglucanase 10 and 25 and mannose-1-phosphate guanyltransferase subunits alpha and beta. This is the first large scale characterization of the proteome of a plant rhizome. Implications of the findings were discussed in relation to other underground organs and related

  14. Vascular Cures

    Science.gov (United States)

    ... is Possible EVERY DOLLAR SAVES LIVES. Donate Now Vascular Cures innovates patient-centered research, catalyzes breakthrough collaborations and empowers people in their vascular health journey. what is vascular disease PATIENTS see ...

  15. Vascular ring

    Science.gov (United States)

    ... subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... Vascular ring is rare. It accounts for less than 1% of all congenital heart problems. The condition ...

  16. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Science.gov (United States)

    Debrah, Alexander Yaw; Mand, Sabine; Specht, Sabine; Marfo-Debrekyei, Yeboah; Batsa, Linda; Pfarr, Kenneth; Larbi, John; Lawson, Bernard; Taylor, Mark; Adjei, Ohene; Hoerauf, Achim

    2006-09-01

    Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of

  17. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Alexander Yaw Debrah

    2006-09-01

    Full Text Available Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS, dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(sVEGFR-3]. Lymphedema patients were additionally monitored for stage (grade of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with

  18. Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Tong Yin; Xiao-Long Ji; Min-Shi Shen

    2003-01-01

    AIM: To elucidate the relationship between lymph nodesinuses with blood and lymphatic metastasis of gastric cancer.METHODS: Routine autopsy was carried out in the randomlyselected 102 patients (among them 100 patients died ofvarious diseases, and 2 patients died of non-diseasedreasons), their superficial lymph nodes locating in bilateralnecks (include supraclavicle), axilla, inguina, thorax, andabdomen were sampled. Haematoxylin-Eosin staining wasperformed on 10 % formalin-fixed and paraffin-embeddedlymph node tissue sections (Sum). The histological pattemsof the lymph sinuses containing blood were observed underlight microscope. The expression of CD31, a marker forendothelial cell, was detected both in blood and non-bloodcontaining lymph node sinuses with the method ofimmunohistochemistry.RESULTS: Among the 1322 lymph nodes sampled fromthe autopsies of 100 diseased cases, lymph node sinusescontaining blood were found in 809 lymph nodes sampledfrom 91 cases, but couldn't be seen in the lymph nodessampled from the non-diseased cases. According to histology,we divided the blood containing lymph node sinuses intofive categories: vascular-opening sinus, blood-deficient sinus,erythrophago-sinus, blood-abundant sinus, vascular-formative sinus. Immunohistochemical findings showed thatthe expression of CD31 was strongly positive in vascular-formative sinuses and some vascular-opening sinuses whileit was faint in blood-deficient sinuses, erythrophago-sinusesand some vascular-opening sinuses. It was almost negativein blood-abundant sinus and non-blood containing sinus.CONCLUSION: In the state of disease, the phenomenonof blood present in the lymph sinus is not uncommon. Bloodcould possibly enter into the lymph sinuses through thelymphaticovenous communications between the veins andthe sinuses in the node. Lymph circulation and the bloodcirculation could communicate with each other in the lymphnode sinuses. The skipping and distal lymphatic metastasisof gastric cancer may

  19. Venolymphatic vascular malformation of the parotid gland extending into the parapharyngeal space: A rare presentation

    Science.gov (United States)

    Khatib, Yasmeen; Dande, Madhura; Patel, Richa D; Gite, Vinod

    2016-01-01

    Vascular malformations (VMs) are structural malformations of vascular development causing soft tissue abnormality with functional and esthetic impairment. They are named by their predominant vessel type as arterial, venous, lymphatic or mixed types. VMs of the parotid gland are extremely rare and constitute a distinct entity of parotid pathology that requires specific diagnostic tools and management. Till 2013, only fifty cases of VMs of the parotid have been described in the literature. We present a case of a venolymphatic malformation of the parotid gland extending into the parapharyngeal space in a 21-year-old male who presented with a swelling on the left side of the face extending into the neck. Diagnosis was suggested by ultrasonography and computed tomography scan and was confirmed by magnetic resonance imaging examination. Complete surgical excision of the lesion was done with a favorable outcome. Diagnosis was confirmed based on histopathology and immunohistochemical studies. PMID:27601828

  20. Venolymphatic vascular malformation of the parotid gland extending into the parapharyngeal space: A rare presentation

    Directory of Open Access Journals (Sweden)

    Yasmeen Khatib

    2016-01-01

    Full Text Available Vascular malformations (VMs are structural malformations of vascular development causing soft tissue abnormality with functional and esthetic impairment. They are named by their predominant vessel type as arterial, venous, lymphatic or mixed types. VMs of the parotid gland are extremely rare and constitute a distinct entity of parotid pathology that requires specific diagnostic tools and management. Till 2013, only fifty cases of VMs of the parotid have been described in the literature. We present a case of a venolymphatic malformation of the parotid gland extending into the parapharyngeal space in a 21-year-old male who presented with a swelling on the left side of the face extending into the neck. Diagnosis was suggested by ultrasonography and computed tomography scan and was confirmed by magnetic resonance imaging examination. Complete surgical excision of the lesion was done with a favorable outcome. Diagnosis was confirmed based on histopathology and immunohistochemical studies.

  1. Caution is recommended prior to sildenafil use in vascular anomalies.

    Science.gov (United States)

    Rankin, Hannah; Zwicker, Kelley; Trenor, Cameron C

    2015-11-01

    Since publication of a single case report of lymphatic malformation improvement during sildenafil therapy for pulmonary hypertension, sildenafil use has propagated across multiple vascular anomalies diagnoses. Vascular anomalies are rare conditions, often with poor long-term outcomes from available therapies, making these patients vulnerable to novel therapy use. We have retrospectively reviewed 14 children with vascular anomalies treated with sildenafil. None of these patients reported improvement of disease while on treatment and some reported side effects including infections and bleeding. Pending more convincing prospective data, we recommend caution prior to sildenafil use for vascular anomalies.

  2. Development of an Open Source Image-Based Flow Modeling Software - SimVascular

    Science.gov (United States)

    Updegrove, Adam; Merkow, Jameson; Schiavazzi, Daniele; Wilson, Nathan; Marsden, Alison; Shadden, Shawn

    2014-11-01

    SimVascular (www.simvascular.org) is currently the only comprehensive software package that provides a complete pipeline from medical image data segmentation to patient specific blood flow simulation. This software and its derivatives have been used in hundreds of conference abstracts and peer-reviewed journal articles, as well as the foundation of medical startups. SimVascular was initially released in August 2007, yet major challenges and deterrents for new adopters were the requirement of licensing three expensive commercial libraries utilized by the software, a complicated build process, and a lack of documentation, support and organized maintenance. In the past year, the SimVascular team has made significant progress to integrate open source alternatives for the linear solver, solid modeling, and mesh generation commercial libraries required by the original public release. In addition, the build system, available distributions, and graphical user interface have been significantly enhanced. Finally, the software has been updated to enable users to directly run simulations using models and boundary condition values, included in the Vascular Model Repository (vascularmodel.org). In this presentation we will briefly overview the capabilities of the new SimVascular 2.0 release. National Science Foundation.

  3. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

    Science.gov (United States)

    Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

    2014-02-01

    In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  4. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice

    Directory of Open Access Journals (Sweden)

    Dilu Feng

    2014-02-01

    Full Text Available In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE+ and without luminal epithelium (LE− were transplanted from transgenic green-fluorescent-protein-positive (GFP+ donor mice into the dorsal skinfold chamber of GFP− wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE− fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE+ fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE+ lesions compared with LE− lesions. In addition, we found that many GFP+ microvessels grew outside the LE− lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  5. Lymphatics and lymphatic-like structures in melanoma : a pathobiological study

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

    Solid malignant tumors can be regarded as a functional tissue in which architecture and function are maintained by a dynamic interplay between tumor cells and a microenvironment consisting of extracellular matrix (ECM) containing fibroblasts, blood and lymphatic vasculature and infiltrating and resi

  6. Lymphatics and lymphatic-like structures in melanoma : a pathobiological study

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

    Solid malignant tumors can be regarded as a functional tissue in which architecture and function are maintained by a dynamic interplay between tumor cells and a microenvironment consisting of extracellular matrix (ECM) containing fibroblasts, blood and lymphatic vasculature and infiltrating and resi

  7. OVEREXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND THE DEVELOPMENT OF POST-TRANSPLANTATION CANCER

    Science.gov (United States)

    Basu, Aninda; Contreras, Alan G.; Datta, Dipak; Flynn, Evelyn; Zeng, Liling; Cohen, Herbert T.; Briscoe, David M.; Pal, Soumitro

    2009-01-01

    Cancer is an increasing and major problem following solid organ transplantation. In part, the increased cancer risk is associated with the use of immunosuppressive agents, especially calcineurin inhibitors. We propose that the effect of calcineurin inhibitors on the expression of vascular endothelial growth factor (VEGF) leads to an angiogenic milieu that favors tumor growth. Here, we used 786-0 human renal cancer cells to investigate the effect of Cyclosporine (CsA) on VEGF expression. Utilizing a full-length VEGF promoter-luciferase construct, we found that CsA markedly induced VEGF transcriptional activation through the PKC signaling pathway, specifically involving PKCζ and PKCδ isoforms. Moreover, CsA promoted the association of PKCζ and PKCδ with the transcription factor Sp1 as observed by immunoprecipitation assays. Using promoter deletion constructs, we found that CsA-mediated VEGF transcription was primarily Sp1-dependent. Furthermore, CsA-induced and PKC-Sp1-mediated VEGF transcriptional activation was partially inhibited by pVHL. CsA also promoted the progression of human renal tumors in vivo, where VEGF is overexpressed. Finally, to evaluate the in vivo significance of CsA-induced VEGF overexpression in terms of post-transplantation tumor development, we injected CT26 murine carcinoma cells (known to form angiogenic tumors) into mice with fully MHC mismatched cardiac transplants. We observed that therapeutic doses of CsA increased tumor size, VEGF mRNA expression, and also enhanced tumor angiogenesis. However, co-administration of a blocking anti-VEGF antibody inhibited this CsA-mediated tumor growth. Collectively, these findings define PKC-mediated VEGF transcriptional activation as a key component in the progression of CsA-induced post-transplantation cancer. PMID:18632621

  8. The role of Smad signaling in vascular and hematopoietic development revealed by studies using genetic mouse models

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Smads are intracellular mediators of transforming growth factor β (TGF-β) superfamily signaling. In this review, we focus on the genetic mouse models for Smad pathways, which have provided functional evidence regarding the complex circuitry in angiogenesis and hematopoiesis during development. In the early stages of vascular development, TGF-β signaling is a contri buting factor in angiogenesis and vascular maturation. Whereas in the later embryogenesis, selected molecules of Smad pathways, such as TGF-β type II receptor (TbRII), ALK5, and Smad5, seem to be dispensable for vessel morphogenesis and integrity. TGF-β signaling is not required in the induction of hematopoietic precursors from mesoderm, but inhibits the subsequent expansion of committed hematopoietic precursors. By contrast, bone morphogenetic protein 4 (BMP4) has long been acknowledged pivotal in mesoderm induction and hematopoietic commitment during development. However, recent genetic evidence shows the BMP4-ALK3 axis is not crucial for the formation of hematopoietic cells from FLK1+ mesoderm. Because of the highly redundant mechanisms within the Smad pathways, the precise role of the Smad signaling involved in vascular and hematopoietic development remains nebulous. The generation of novel cell lineage restricted Cre transgenes would shed new light on the future relevant investigations.

  9. Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses

    Directory of Open Access Journals (Sweden)

    Rui-Cheng Ji

    2016-12-01

    Full Text Available The lymphatic system is essential for transporting interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs. Functional integrity of LNs is dependent on intact lymphatics and effective lymph drainage. Molecular mechanisms that facilitate interactions between tumor cells and lymphatic endothelial cells (LECs during tumor progression still remain to be identified. The cellular and molecular structures of LNs are optimized to trigger a rapid and efficient immune response, and to participate in the process of tumor metastasis by stimulating lymphangiogenesis and establishing a premetastatic niche in LNs. Several molecules, e.g., S1P, CCR7-CCL19/CCL21, CXCL12/CXCR4, IL-7, IFN-γ, TGF-β, and integrin α4β1 play an important role in controlling the activity of LN stromal cells including LECs, fibroblastic reticular cells (FRCs and follicular dendritic cells (DCs. The functional stromal cells are critical for reconstruction and remodeling of the LN that creates a unique microenvironment of tumor cells and LECs for cancer metastasis. LN metastasis is a major determinant for the prognosis of most human cancers and clinical management. Ongoing work to elucidate the function and molecular regulation of LN lymphatic sinuses will provide insight into cancer development mechanisms and improve therapeutic approaches for human malignancy.

  10. Divergence of zebrafish and mouse lymphatic cell fate specification pathways

    DEFF Research Database (Denmark)

    van Impel, Andreas; Zhao, Zhonghua; Hermkens, Dorien M A;

    2014-01-01

    . Murine Prox1-null embryos lack lymphatic structures, and sustained expression of Prox1 is indispensable for the maintenance of lymphatic cell fate even at adult stages, highlighting the unique importance of this gene for the lymphatic lineage. Whether this pre-eminent role of Prox1 within the lymphatic...... vasculature is conserved in other vertebrate classes has remained unresolved, mainly owing to the lack of availability of loss-of-function mutants. Here, we re-examine the role of Prox1a in zebrafish lymphangiogenesis. First, using a transgenic reporter line, we show that prox1a is initially expressed...... that the functionally related transcription factors Coup-TFII and Sox18 are also dispensable for lymphangiogenesis. Together, these findings suggest that lymphatic commitment in zebrafish and mice is controlled in fundamentally different ways....

  11. The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

    Science.gov (United States)

    Hitscherich, Kyle; Smith, Kyle; Cuoco, Joshua A; Ruvolo, Kathryn E; Mancini, Jayme D; Leheste, Joerg R; Torres, German

    2016-03-01

    The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

  12. Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration.

    Science.gov (United States)

    Miyashita, Takenori; Burford, James L; Hong, Young-Kwon; Gevorgyan, Haykanush; Lam, Lisa; Mori, Nozomu; Peti-Peterdi, Janos

    2013-10-25

    We clarified the localization of lymphatic vessels in the tympanic membrane and proliferation of lymphatic vessels during regeneration after perforation of the tympanic membrane by using whole-mount imaging of the tympanic membrane of Prox1 GFP mice. In the pars tensa, lymphatic vessel loops surrounded the malleus handle and annulus tympanicus. Apart from these locations, lymphatic vessel loops were not observed in the pars tensa in the normal tympanic membrane. Lymphatic vessel loops surrounding the malleus handle were connected to the lymphatic vessel loops in the pars flaccida and around the tensor tympani muscle. Many lymphatic vessel loops were detected in the pars flaccida. After perforation of the tympanic membrane, abundant lymphatic regeneration was observed in the pars tensa, and these regenerated lymphatic vessels extended from the lymphatic vessels surrounding the malleus at day 7. These results suggest that site-specific lymphatic vessels play an important role in the tympanic membrane.

  13. Scholars and scientists in the history of the lymphatic system.

    Science.gov (United States)

    Natale, Gianfranco; Bocci, Guido; Ribatti, Domenico

    2017-09-01

    The discovery of the lymphatic system has a long and fascinating history. The interest in anatomy and physiology of this system paralleled that of the blood cardiocirculatory system and has been maybe obscured by the latter. Paradoxically, if the closed blood system appeared open in Galen's anatomy and physiology, and took a very long time to be correctly described in terms of pulmonary and general circulation by ibn Al-Nafis/Michael Servetus/Realdo Colombo and William Harvey, respectively, the open lymphatic system was incorrectly described as a closed circuit connected with arteries and veins. In ancient times only macroscopic components of the lymphatic system have been described, although misinterpreted, including lymph nodes and lacteals, the latter being easily identified because of their milk-like content. For about 15 centuries the dogmatic acceptance of Galen's notions did not allow a significant progress in medicine. After Vesalius' revolution in anatomical studies, new knowledge was accumulated, and the 17th century was the golden age for the investigation of the lymphatic system with several discoveries: gut lacteals (Gaspare Aselli), cloacal bursa (Hieronimus Fabricius of Acquapendente), reservoir of the chyle (Jean Pecquet), extra-intestinal lymphatic vessels (Thomas Bartholin and Olaus Rudbeck dispute), hepatic lymph circulation (Francis Glisson). In the Enlightenment century Frederik Ruysch described the function of lymphatic valves, and Paolo Mascagni provided a magnificent iconography of the lymphatic network in humans. In recent times, Leonetto Comparini realized three-dimensional reconstructions of the liver lymphatic vessels, and Kari Alitalo discovered the lymphatic growth factor/receptor system. Far from a complete understanding of its anatomy and function, the lymphatic system still needs to be profoundly examined. © 2017 Anatomical Society.

  14. Total lymphatic irradiation and bone marrow in human heart transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  15. Cardiovascular alterations at different stages of hypertension development during ethanol consumption: Time-course of vascular and autonomic changes

    Energy Technology Data Exchange (ETDEWEB)

    Crestani, Carlos C. [Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, Univ. Estadual Paulista—UNESP (Brazil); Lopes da Silva, Andréia [Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Scopinho, América A. [Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Ruginsk, Silvia G.; Uchoa, Ernane T. [Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Correa, Fernando M.A. [Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Elias, Lucila L.K.; Antunes-Rodrigues, José [Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil); Resstel, Leonardo B.M., E-mail: leoresstel@yahoo.com.br [Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo (Brazil)

    2014-10-15

    The aim of the present work was to establish a time-course correlation between vascular and autonomic changes that contribute to the development of hypertension during ethanol ingestion in rats. For this, male Wistar rats were subjected to the intake of increasing ethanol concentrations in their drinking water during four weeks. Ethanol effects were investigated at the end of each week. Mild hypertension was already observed at the first week of treatment, and a progressive blood pressure increase was observed along the evaluation period. Increased pressor response to phenylephrine was observed from first to fourth week. α{sub 1}-adrenoceptor protein in the mesenteric bed was enhanced at the first week, whereas β{sub 2}-adrenoceptor protein in the aorta was reduced after the second week. In the third week, ethanol intake facilitated the depressor response to sodium nitroprusside, whereas in the fourth week it reduced nitrate content in aorta and increased it plasma. The bradycardic component of the baroreflex was impaired, whereas baroreflex tachycardia was enhanced at the third and fourth weeks. AT{sub 1A} receptor and C-type natriuretic peptide (CNP) mRNAs in the nucleus tractus solitarius were increased at the fourth week. These findings suggest that increased vascular responsiveness to vasoconstrictor agents is possibly a link factor in the development and maintenance of the progressive hypertension induced by ethanol consumption. Additionally, baroreflex changes are possibly mediated by alterations in angiotensinergic mechanisms and CNP content within the brainstem, which contribute to maintaining the hypertensive state in later phases of ethanol ingestion. Facilitated vascular responsiveness to nitric oxide seems to counteract ethanol-induced hypertension. - Highlights: • Mild hypertension was observed during the entire period of ethanol ingestion. • Ethanol facilitated vascular reactivity to vasoactive agents. • Changes in baroreflex activity

  16. Fucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells.

    Science.gov (United States)

    Yang, Yazong; Gao, Zixiang; Ma, Yanhong; Teng, Hongming; Liu, Zundong; Wei, Hengyun; Lu, Yanbing; Cheng, Xiaofang; Hou, Lin; Zou, Xiangyang

    2016-06-21

    Lymphangiogenesis is one of the promoters of tumor lymphatic metastasis. Fucoidan which is a fucose-enriched sulfated polysaccharide has effect on various pharmacological activities including anti-metastasis activity. However, the inhibitory effect of fucoidan on lymphangiogenesis remains unclear. Here, fucoidan extracted from U. pinnatifida sporophylls suppressed HLECs proliferation, migration and tube-like structure formation, and had inhibitory effect of tumor-induced lymphangiogenesis in vitro. Additionally, we found that fucoidan had a dose-dependent depressive effect on the expressions of PROX1, vascular endothelial growth factor receptor 3 (VEGFR3), NF-κB, phospho-PI3K and phospho-Akt in HLECs. Moreover, anti-lymphangiogenesis effect of fucoidan was assessed by using mouse tumor model. In summary, fucoidan inhibit tumor lymphangiogenesis and lymphatic metastasis by suppressing the NF-κB/PI3K/Akt signaling pathway through reduced levels of PROX1 and VEGFR3.

  17. Notch2 and Notch3 Function Together to Regulate Vascular Smooth Muscle Development

    OpenAIRE

    Qingqing Wang; Ning Zhao; Simone Kennard; Brenda Lilly

    2012-01-01

    Notch signaling has been implicated in the regulation of smooth muscle differentiation, but the precise role of Notch receptors is ill defined. Although Notch3 receptor expression is high in smooth muscle, Notch3 mutant mice are viable and display only mild defects in vascular patterning and smooth muscle differentiation. Notch2 is also expressed in smooth muscle and Notch2 mutant mice show cardiovascular abnormalities indicative of smooth muscle defects. Together, these findings infer that N...

  18. Vascular Diseases

    Science.gov (United States)

    The vascular system is the body's network of blood vessels. It includes the arteries, veins and capillaries that carry ... to and from the heart. Problems of the vascular system are common and can be serious. Arteries ...

  19. Periportal low-attenuation: a CT sign of lymphatic obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Kim, Chong Soo; Yang, Doo Hyun; Lee, Sang Yong; Lee, Young Whan; Chung, Gyung Ho; Han, Young Min; Sohn, Myung Hee; Choi, Ki Chul [Chonbuk National University College of Medicine, Jeonju (Korea, Republic of)

    1995-07-15

    Periportal low attenuation, defined as a low attenuation rim around the portal vein and its branches which is seen on contrast material-enhanced CT scans, has been described in a variety of conditions. We tried to document that lymphatic obstruction is one of the major cause of periportal low attenuation. We retrospectively analyzed 57 cases of periportal low attenuation of abdominal CT scans and also reviewed the surgical records in 32 cases. Lymph node enlargement in the hepatoduodenal ligament which is a main lymphatic channel from the liver were analyzed the calculated the ratio of the transeverse diameter between the inferior vena cava and the aorta at the level of right adrenal gland. After complete surgical interruption of the lymphatic drainage from the liver in a dog, follow up CT scans were obtained and correlated with pathologic findings. Fifty patients (88%) had underlying disease which could cause impairment of lymphatic drainage. Periportal low attenuation was identified in several clinical conditions, including surgical lymph node dissection, lymphadenopathy in the hepatoduodenal ligament, blunt trauma. In animal model, CT scan showed prominent periportal low attenuation at 5 days after surgery. Histologic examination revealed numerous dilated lymphatic vessels and a marked lymphedema in the connective tissues surrounding the portal vein and its major branches. One of the major cause of periportal low attenuation was impaired lymphatic drainage and periportal low attenuation corresponding to the numerous dilated lymphatic vessels and a marked lymphedema in the connective tissues surrounding the portal vein and its major branches.

  20. Itching for answers: how histamine relaxes lymphatic vessels.

    Science.gov (United States)

    Scallan, Joshua P; Davis, Michael J

    2014-10-01

    In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow-induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology.

  1. The effect of lymphatic valve morphology on fluid transport

    Science.gov (United States)

    Alexeev, Alexander; Ballard, Matthew; Nepiyushchikh, Zhanna; Dixon, Brandon

    2016-11-01

    The lymphatic vasculature is present in nearly all invertebrate tissue, and is essential in the transport of fluid and particles such as immune cells, antigens, proteins and lipids from the tissue to lymph nodes and to the venous circulation. Lymphatic vessels are made of up a series of contractile units that work together in harmony as "micro hearts" to pump fluid against a pressure gradient. Lymphatic valves are critical to this functionality, as they open and close with the oscillating pressure gradients from contractions, thus allowing flow in only one direction and leading to a net pumping effect. We use a hybrid lattice-Boltzmann lattice spring model which captures fluid-solid interactions through two-way coupling between a viscous fluid and lymphatic valves in a section of a lymphatic vessel to study the dynamics of lymphatic valves and their effect on fluid transport. Further, we investigate the effect of variations in valve geometry and material properties on fluid pumping. This work helps to increase our understanding of the mechanisms of lymphatic fluid transport, which has implications in a variety of pathologies, including cancer metastasis, autoimmunity, atherosclerosis and obesity. Support from NSF CMMI 1635133 is gratefully acknowledged.

  2. Vascular Vertigo

    OpenAIRE

    Mazyar Hashemilar; Masoud Nikanfar; Dariush Savadi Oskoui

    2017-01-01

    Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vert...

  3. Paravertebral vascular hamartoma - radiological findings; Hamartoma vascular paravertebral - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Maria Cristina Soares dos; Dinoa, Vanessa de Albuquerque; Borges, Aurea Valeria Rosa Mohana; Teixeira, Sonia [Hospital Universitario Antonio Pedro (HUAP), Niteroi, RJ (Brazil). Secao de Radiologia; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Monteiro, Elio [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Cirurgia

    1997-01-01

    Hamartomas are benign tumours that can occur in different organs and tissues. They consist of an abnormal increase of cells and tissues common to the organ from which they arise. When they occur in lymphatic and blood vessels they are called vascular hamartomas. These tumours are frequent in the central nervous system, giving rise to hemorrhages. The authors report a case of vascular hamartoma in the right paravertebral gutter with an intradural component that caused a spinal cord compression and paraplegia. A malignant lesion was suggested based on the clinical and radiological findings. (author) 14 refs., 4 figs.

  4. Development and evaluation of elastomeric hollow fiber membranes as small diameter vascular graft substitutes

    Energy Technology Data Exchange (ETDEWEB)

    Mercado-Pagán, Ángel E.; Kang, Yunqing [Department of Orthopedic Surgery, Stanford University, Stanford, CA (United States); Findlay, Michael W. [Department of Plastic and Reconstructive Surgery, Stanford University, Stanford, CA (United States); University of Melbourne Department of Surgery, Royal Melbourne Hospital, Parkville, VIC (Australia); Yang, Yunzhi, E-mail: ypyang@stanford.edu [Department of Orthopedic Surgery, Stanford University, Stanford, CA (United States); Department of Materials Science and Engineering, Stanford University, Stanford, CA (United States)

    2015-04-01

    Engineering of small diameter (< 6 mm) vascular grafts (SDVGs) for clinical use remains a significant challenge. Here, elastomeric polyester urethane (PEU)-based hollow fiber membranes (HFMs) are presented as an SDVG candidate to target the limitations of current technologies and improve tissue engineering designs. HFMs are fabricated by a simple phase inversion method. HFM dimensions are tailored through adjustments to fabrication parameters. The walls of HFMs are highly porous. The HFMs are very elastic, with moduli ranging from 1–4 MPa, strengths from 1–5 MPa, and max strains from 300–500%. Permeability of the HFMs varies from 0.5–3.5 × 10{sup −6} cm/s, while burst pressure varies from 25 to 35 psi. The suture retention forces of HFMs are in the range of 0.8 to 1.2 N. These properties match those of blood vessels. A slow degradation profile is observed for all HFMs, with 71 to 78% of the original mass remaining after 8 weeks, providing a suitable profile for potential cellular incorporation and tissue replacement. Both human endothelial cells and human mesenchymal stem cells proliferate well in the presence of HFMs up to 7 days. These results demonstrate a promising customizable PEU HFMs for small diameter vascular repair and tissue engineering applications. - Highlights: • Hollow fiber membranes (HFMs) were fabricated and evaluated. • HFM properties could be tailored through adjustments to fabrication parameters. • Properties could match or exceed those of blood vessels. • HFM showed excellent compatibility in vitro. • HFMs have the potential to be used for small diameter vascular grafts.

  5. Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury.

    Science.gov (United States)

    Han, Xiao-Jian; Chen, Min; Hong, Tao; Zhu, Ling-Yu; He, Dan; Feng, Jiu-Geng; Jiang, Li-Ping

    2015-04-01

    Percutaneous coronary intervention [PCI or percutaneous transluminal coronary angioplasty (PTCA)] has been developed into a mature interventional treatment for atherosclerotic cardiovascular disease. However, the long-term therapeutic effect is compromised by the high incidence of vascular restenosis following angioplasty, and the underlying mechanisms of vascular restenosis have not yet been fully elucidated. In the present study, we investigated the role of the gap junction (GJ) protein, connexin 43 (Cx43), in the development of vascular restenosis. To establish vascular restenosis, rat carotid arteries were subjected to balloon angioplasty injury. At 0, 7, 14 and 2 days following balloon injury, the arteries were removed, and the intimal/medial area of the vessels was measured to evaluate the degree of restenosis. We found that the intimal area gradually increased following balloon injury. Intimal hyperplasia and restenosis were particularly evident at 14 and 28 days after injury. In addition, the mRNA and protein expression of Cx43 was temporarily decreased at 7 days, and subsequently increased at 14 and 28 days following balloon injury, as shown by RT-PCR and western blot analysis. To determine the involvement of Cx43 in vascular restenosis, the lentivirus vector expressing shRNA targeting Cx43, Cx43-RNAi-LV, was used to silence Cx43 in the rat carotid arteries. The knockdown of Cx43 effectively attenuated the development of intimal hyperplasia and vascular restenosis following balloon injury. Thus, our data indicate the vital role of the GJ protein, Cx43, in the development of vascular restenosis, and provide new insight into the pathogenesis of vascular restenosis. Cx43 may prove to be a novel potential pharmacological target for the prevention of vascular restenosis following PCI.

  6. Uterine and placenta characteristics during early vascular development in the pig from day 22 to 42 of gestation.

    Science.gov (United States)

    Wright, Elane C; Miles, Jeremy R; Lents, Clay A; Rempel, Lea A

    2016-01-01

    Insufficient placenta development is one of the primary causes of fetal death and reduced fetal growth after 35 days of gestation. Between day 22 and 42 the placenta consists of a central highly vascular placenta (HVP), adjacent to the fetus, a less vascular placenta (LVP), on either side of the fetus, and necrotic tips (NT). The objective of this study was to comprehensively evaluate uterine-placenta characteristics during early gestation in the gilt and determine time points and physiological changes. Gilts (n=25) were artificially inseminated at first detection of estrus (day 0) and 24h later, and harvested at 22, 27, 32, 37 or 42 days of gestation. Litter size, 12.1±3.4, was similar for all days of gestation. Fetal and placenta weight increased with day of gestation. The greatest increase in placenta weight occurred between 37 and 42 days of gestation. The LVP zones had no measurable fold formation until day 27. Necrotic tips became apparent after 27 days of gestation. Unoccupied areas of the uterus developed folds with changes in endometrial cell size and morphology from day 32 to 42 of gestation. Limited changes occurred in either fetal growth or placenta weight from day 27 through 32 of gestation; however, significant morphological changes occur at the maternal-fetal interface, demonstrating the dynamic architecture of the developing porcine placenta during early gestation. This work establishes fundamental time points in placenta development corresponding to fetal growth and microfold formation that may influence fetal growth and impact fetal survival.

  7. PlexinD1 is required for proper patterning of the periocular vascular network and for the establishment of corneal avascularity during avian ocular development.

    Science.gov (United States)

    Kwiatkowski, Sam C; Ojeda, Ana F; Lwigale, Peter Y

    2016-03-01

    The anterior eye is comprised of an avascular cornea surrounded by a dense periocular vascular network and therefore serves as an excellent model for angiogenesis. Although signaling through PlexinD1 underlies various vascular patterning events during embryonic development, its role during the formation of the periocular vascular network is yet to be determined. Our recent study showed that PlexinD1 mRNA is expressed by periocular angioblasts and blood vessels during ocular vasculogenesis in patterns that suggest its involvement with Sema3 ligands that are concurrently expressed in the anterior eye. In this study, we used in vivo knockdown experiments to determine the role of PlexinD1 during vascular patterning in the anterior eye of the developing avian embryos. Knockdown of PlexinD1 in the anterior eye caused mispatterning of the vascular network in the presumptive iris, which was accompanied by lose of vascular integrity and profuse hemorrhaging in the anterior chamber. We also observed ectopic vascularization of the cornea in PlexinD1 knockdown eyes, which coincided with the formation of the limbal vasculature in controls. Finally we show that Sema3E and Sema3C transcripts are expressed in ocular tissue that is devoid of vasculature. These results indicate that PlexinD1 plays a critical role during vascular patterning in the iris and limbus, and is essential for the establishment of corneal avascularity during development. We conclude that PlexinD1 is involved in vascular response to antiangiogenic Sema3 signaling that guides the formation of the iris and limbal blood vessels by inhibiting VEGF signaling.

  8. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia.

    Science.gov (United States)

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C

    2015-03-01

    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P epithelium. Hyperoxia reduced alveolarization in WT mice (P lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors.

  9. Hemodynamics, inflammation, vascular remodeling, and the development and rupture of intracranial aneurysms: a review

    Directory of Open Access Journals (Sweden)

    Francesco Signorelli

    2015-06-01

    Full Text Available The central nervous system is an immunologically active environment where several components of the immune and inflammatory response interact among them and with the constituents of nervous tissue and vasculature in a critically orchestrated manner, influencing physiologic and pathologic processes. In particular, inflammation takes a central role in the pathogenesis of intracranial aneurysms (IAs. The common pathway for aneurysm formation involves endothelial dysfunction and injury, a mounting inflammatory response, vascular smooth muscle cells (VSMCs phenotypic modulation, extracellular matrix remodeling, and subsequent cell death and vessel wall degeneration. We conducted a literature review (1980-2014 by Medline and EMBASE databases using the searching terms "IA" and "cerebral aneurysm" and further search was performed to link the search terms with the following key words: inflammation, hemodynamic(s, remodeling, macrophages, neutrophils, lymphocytes, complement, VSMCs, mast cells, cytokines, and inflammatory biomarkers. The aim of this review was to summarize the most recent and pertinent evidences regarding the articulated processes of aneurysms formation, growth, and rupture. Knowledge of these processes may guide the diagnosis and treatment of these vascular malformations, the most common cause of subarachnoid hemorrhage, which prognosis remains dismal.

  10. Polydopamine-mediated immobilization of multiple bioactive molecules for the development of functional vascular graft materials.

    Science.gov (United States)

    Lee, Yu Bin; Shin, Young Min; Lee, Ji-Hye; Jun, Indong; Kang, Jae Kyeong; Park, Jong-Chul; Shin, Heungsoo

    2012-11-01

    In this study, we introduced a simple method for polydopamine-mediated immobilization of dual bioactive factors for the preparation of functionalized vascular graft materials. Polydopamine was deposited on elastic and biodegradable poly(lactic acid-co-ɛ-caprolactone) (PLCL) films, and a cell adhesive RGD-containing peptide and basic fibroblast growth factor were subsequently immobilized by simple dipping. We used an enzyme-linked immunosorbent assay and fluorescamine assay to confirm that we had stably immobilized bioactive molecules on the polydopamine-coated PLCL film in a reaction time-dependent manner. When human umbilical vein endothelial cells (HUVEC) were cultured on the prepared substrates, the number of adherent cells and proliferation of HUVEC for up to 14 days were greatest on the film immobilized with dual factors. On the other hand, the film immobilized with RGD peptide exhibited the highest migration speed compared to the other groups. The expression of cluster of differentiation 31 and von Willebrand factor, which indicates maturation of endothelial cells, was highly stimulated in the dual factor-immobilized group, and passively adsorbed factors showed a negligible effect. The immobilization of bioactive molecules inspired by polydopamine was successful, and adhesion, migration, proliferation and differentiation of HUVEC were synergistically accelerated by the presence of multiple signaling factors. Collectively, our results have demonstrated that a simple coating with polydopamine enables the immobilization of multiple bioactive molecules for preparation of polymeric functionalized vascular graft materials. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. [Role of master transcriptional factor Prox-1 in lymphatic endothelial differentiation of Kaposiform hemangioendothelioma].

    Science.gov (United States)

    Ke, Z Y; Yang, S J

    2017-03-08

    Objective: To analyze the clinical and pathological features of Kaposiform hemangioendothelioma (KHE), and to investigate the role of master transcriptional factor Prox-1 in the regulation of lymphatic differentiation. Methods: Nine cases of KHE (during the period from October 2009 to June 2016) were collected with clinical and pathological data. H&E stained section review and immunohistochemietry using the Dako EnVision method were performed. Results: There were 6 female and 3 male patients with age ranging from 2 months to 8 years (median 3 years and 4 months). The patients presented with either single subcutaneous soft tissue mass, or bone tumors, with the duration of disease onset ranging from 1 month to 1 year. The sites of involvement included the skins of neck (2 cases), nose root (1 case), inguinal (1 case), thigh root (1 case), humerus (2 cases), lumbar vertebrae(1 case), and mesentery (1 case). These tumors were histologically composed of nodules of densely packed spindle or ovoid cells and deformed small blood vessels in an invasive growth pattern. The tumor cells were immunohistochemically positive for both blood vessels and lymphatic endothelial markers, including Prox-1, the master transcriptional factor, and VEGFR-3. With followed-up from 1 to 60 months (median 26 months), two patients died of the disease, while the remaining patients were alive without recurrence. Conclusions: KHE is a rare vascular tumor with at least partial lymphatic endothelial differentiation, in which Prox-1 may act as a master regulator for such differentiation. KHE is an aggressive tumor of intermediate malignant potential, with local invasion and recurrence tendency, and long term follow-up is required.

  12. Lymphatic Expression of CLEVER-1 in Breast Cancer and Its Relationship with Lymph Node Metastasis

    Directory of Open Access Journals (Sweden)

    Aula Ammar

    2011-01-01

    Full Text Available Background: Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1 in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. Methods: 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC, CD209 (immature DC, iDC and CD68 (macrophage, M&phis;. in vitro expression of CLEVER-1 on lymphatic (LEC and blood endothelial cells (BEC was examined by flow cytometry. Results: in vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples, lymphatic vessels (LV, 18.2% of samples and in M&phis;/DCs (82.4% of samples. However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027 and with M&phis; indices (p = 0.021. Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049. The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001 and LV (p = 0.004. Conclusions: The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN.

  13. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  14. Evaluation of lymphatic regeneration in rat incisional wound healing ...

    African Journals Online (AJOL)

    Nevine M.F. El Deeb

    2014-06-20

    Jun 20, 2014 ... Abstract Objective: During the wound healing process, lymphatic regeneration in the injured skin has not .... posed of newly-formed blood vessels and fibroblasts .... age plays a role in connection with traumatic deaths due to.

  15. NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone

    Directory of Open Access Journals (Sweden)

    Ryan E. Tomlinson

    2016-09-01

    Full Text Available Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkAF592A mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.

  16. Functional analysis of zebrafish microfibril-associated glycoprotein-1 (Magp1) in vivo reveals roles for microfibrils in vascular development and function.

    Science.gov (United States)

    Chen, Eleanor; Larson, Jon D; Ekker, Stephen C

    2006-06-01

    Mutations in fibrillin-1 (FBN1) result in Marfan syndrome, demonstrating a critical requirement for microfibrils in vessel structure and function. However, the identity and function of many microfibril-associated molecules essential for vascular development and function have yet to be characterized. In our morpholino-based screen for members of the secretome required for vascular development, we identified a key player in microfibril formation in zebrafish embryogenesis. Microfibril-associated glycoprotein-1 (MAGP1) is a conserved protein found in mammalian and zebrafish microfibrils. Expression of magp1 mRNA is detected in microfibril-producing cells. Analysis of a functional Magp1-mRFP fusion protein reveals localization along the midline and in the vasculature during embryogenesis. Underexpression and overexpression analyses demonstrate that specific Magp1 protein levels are critical for vascular development. Integrin function is compromised in magp1 morphant embryos, suggesting that reduced integrin-matrix interaction is the main mechanism for the vascular defects in magp1 morphants. We further show that Magp1 and fibrillin-1 interact in vivo. This study implicates MAGP1 as a key player in microfibril formation and integrity during development. The essential role for MAGP1 in vascular morphogenesis and function also supports a wide range of clinical applications, including therapeutic targets in vascular disease and cardiovascular tissue engineering.

  17. [The development of the system of blood flow block by using magnetic compression abdominal large vascular].

    Science.gov (United States)

    Yan, Xiaopeng; Lv, Yi; Ma, Feng; Ma, Jia; Wang, Haohua; Wang, Shanpei; Li, Dichen; Liu, Yaxiong; Jia, Shenli; Shi, Zongqian; Luo, Ruixue

    2014-03-01

    A new system of blood flow block for control of bleeding in abdominal operation is composed of an abdominal magnetic blocking unit, an abdominal external electromagnet unit and other non-magnetic operation instrument. The abdominal external electromagnetic unit is placed in advance in the operation bed. The abdominal magnetic blocking unit can be placed directly on the ventral of the large vessels when need to blocking the abdominal large vessels during the operation. According to the non-contact suction characteristics of magnetic materials, the two magnetic units will attract each other and compression the vessels. Using this system for vascular occlusion does not need clear exposure and without separating vessel. There is the advantage of rapid, accurate and reliable for the system.

  18. Development of an aptamer-based affinity purification method for vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Maren Lönne

    2015-12-01

    Full Text Available Since aptamers bind their targets with high affinity and specificity, they are promising alternative ligands in protein affinity purification. As aptamers are chemically synthesized oligonucleotides, they can be easily produced in large quantities regarding GMP conditions allowing their application in protein production for therapeutic purposes. Several advantages of aptamers compared to antibodies are described in general within this paper. Here, an aptamer directed against the human Vascular Endothelial Growth Factor (VEGF was used as affinity ligand for establishing a purification platform for VEGF in small scale. The aptamer was covalently immobilized on magnetic beads in a controlled orientation resulting in a functional active affinity matrix. Target binding was optimized by introduction of spacer molecules and variation of aptamer density. Further, salt-induced target elution was demonstrated as well as VEGF purification from a complex protein mixture proving the specificity of protein-aptamer binding.

  19. Maternal Retinoids Increase PDGFRα+ Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2017-04-01

    Full Text Available Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA administration expanded PDGFRα+ adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR 2 knock out in PDGFRα+ cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies.

  20. Quantum dots trace lymphatic drainage from the mouse eye

    Energy Technology Data Exchange (ETDEWEB)

    Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H, E-mail: yucely@smh.ca [Department of Ophthalmology and Vision Sciences, University of Toronto, M5T 2S8 (Canada)

    2011-10-21

    Glaucoma is a leading cause of blindness in the world, often associated with elevated eye pressure. Currently, all glaucoma treatments aim to lower eye pressure by improving fluid exit from the eye. We recently reported the presence of lymphatics in the human eye. The lymphatic circulation is known to drain fluid from organ tissues and, as such, lymphatics may also play a role in draining fluid from the eye. We investigated whether lymphatic drainage from the eye is present in mice by visualizing the trajectory of quantum dots once injected into the eye. Whole-body hyperspectral fluorescence imaging was performed in 17 live mice. In vivo imaging was conducted prior to injection, and 5, 20, 40 and 70 min, and 2, 6 and 24 h after injection. A quantum dot signal was observed in the left neck region at 6 h after tracer injection into the eye. Examination of immunofluorescence-labelled sections using confocal microscopy showed the presence of a quantum dot signal in the left submandibular lymph node. This is the first direct evidence of lymphatic drainage from the mouse eye. The use of quantum dots to image this lymphatic pathway in vivo is a novel tool to stimulate new treatments to reduce eye pressure and prevent blindness from glaucoma.

  1. Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish

    DEFF Research Database (Denmark)

    Dahl Ejby Jensen, Lasse; Cao, Renhai; Hedlund, Eva-Maria

    2009-01-01

    The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections...

  2. Epidermal Vascular Endothelial Growth Factor Production Is Required for Permeability Barrier Homeostasis, Dermal Angiogenesis, and the Development of Epidermal Hyperplasia

    Science.gov (United States)

    Elias, Peter M.; Arbiser, Jack; Brown, Barbara E.; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R.

    2008-01-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf−/− mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis. PMID:18688025

  3. Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Rostgaard, Klaus; Askling, Johan;

    2002-01-01

    BACKGROUND: Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low...... the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. METHODS: We identified parents, siblings, and offspring of 17,045 persons...... with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer...

  4. Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development

    Science.gov (United States)

    Holoyda, Kathleen A.; Hou, Xiaogang; Fowler, Kathryn L.; Grikscheit, Tracy C.

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Methods VEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration. Results Increased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2. Conclusions Manipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future

  5. PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation.

    Science.gov (United States)

    Wu, Yaxu; Ferguson, James E; Wang, Hong; Kelley, Rusty; Ren, Rongqin; McDonough, Holly; Meeker, James; Charles, Peter C; Wang, Hengbin; Patterson, Cam

    2008-01-01

    The mechanisms that regulate the differentiation program of multipotential stem cells remain poorly understood. In order to define the cues that delineate endothelial commitment from precursors, we screened for candidate regulatory genes in differentiating mouse embryoid bodies. We found that the PR/SET domain protein, PRDM6, is enriched in flk1(+) hematovascular precursor cells using a microarray-based approach. As determined by 5' RACE, full-length PRDM6 protein contains a PR domain and four Krüppel-like zinc fingers. In situ hybridization in mouse embryos demonstrates staining of the primitive streak, allantois, heart, outflow tract, paraaortic splanchnopleura (P-Sp)/aorto-gonadal-mesonephric (AGM) region and yolk sac, all sites known to be enriched in vascular precursor cells. PRDM6 is also detected in embryonic and adult-derived endothelial cell lines. PRDM6 is co-localized with histone H4 and methylates H4-K20 (but not H3) in vitro and in vivo, which is consistent with the known participation of PR domains in histone methyltransferase activity. Overexpression of PRDM6 in mouse embryonic endothelial cells induces apoptosis by activating caspase-3 and inducing G1 arrest. PRDM6 inhibits cell proliferation as determined by BrdU incorporation in endothelial cells, but not in rat aortic smooth muscle cells. Overexpression of PRDM6 also results in reduced tube formation in cultured endothelial cells grown in Matrigel. Taken together, our data indicate that PRDM6 is expressed by vascular precursors, has differential effects in endothelial cells and smooth muscle cells, and may play a role in vascular precursor differentiation and survival by modulating local chromatin-remodeling activity within hematovascular subpopulations during development.

  6. Low-cost microcontroller platform for studying lymphatic biomechanics in vitro.

    Science.gov (United States)

    Kornuta, Jeffrey A; Nipper, Matthew E; Dixon, J Brandon

    2013-01-04

    The pumping innate to collecting lymphatic vessels routinely exposes the endothelium to oscillatory wall shear stress and other dynamic forces. However, studying the mechanical sensitivity of the lymphatic endothelium remains a difficult task due to limitations of commercial or custom systems to apply a variety of time-varying stresses in vitro. Current biomechanical in vitro testing devices are very expensive, limited in capability, or highly complex; rendering them largely inaccessible to the endothelial cell biology community. To address these shortcomings, the authors propose a reliable, low-cost platform for augmenting the capabilities of commercially available pumps to produce a wide variety of flow rate waveforms. In particular, the Arduino Uno, a microcontroller development board, is used to provide open-loop control of a digital peristaltic pump using precisely timed serial commands. In addition, the flexibility of this platform is further demonstrated through its support of a custom-built cell-straining device capable of producing oscillatory strains with varying amplitudes and frequencies. Hence, this microcontroller development board is shown to be an inexpensive, precise, and easy-to-use tool for supplementing in vitro assays to quantify the effects of biomechanical forces on lymphatic endothelial cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. What Is Vascular Disease?

    Science.gov (United States)

    ... Donors Corporate Sponsors Donor Privacy Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of ... steps to prevent vascular disease here. Understanding the Vascular System Your vascular system – the highways of the ...

  8. Distribution and ultrastructure of the stomata connecting the pleural cavity with lymphatics in the rat costal pleura.

    Science.gov (United States)

    Wang, Q X; Ohtani, O; Saitoh, M; Ohtani, Y

    1997-01-01

    We investigated the detailed distribution and ultrastructure of the stomata connecting the pleural cavity and the lymphatics in the rat costal pleura by scanning electron, transmission electron and light microscopy. The mesothelial cells lining the costal pleura appeared as both flattened and thick cell bodies. The thick cells possessed more rough endoplasmic reticula, Golgi complexes, mitochondria, and free ribosomes than the flattened cells. The thick cells were distributed in the intercostal regions each cephalic to the junction of the costal cartilage and bone, and in the band-like regions along the cephalic and caudal sides of each rib in the lateral and dorsal thoracic walls. In the regions lined with thick cells, there were stomata [12.9 +/- 10.3 microns2 (mean +/- SD) in area] consisting of prolongations of thick mesothelial cells and funnel-like projections of lymphatic endothelial cells that came up along the rims of the pores (5.9 +/- 3.2 microns2 in average area) in the submesothelial collagen fiber network. At the stomata, the basal lamina of the mesothelium was continuous with that of the endothelium. The mesothelial cells forming the stomata were mostly in close contact with the endothelial cells, but some gaps also existed between them. Valve-like endothelial flaps were frequently observed wherever endothelial cells constituting the stomata merged into the submesothelial lymphatics. Also present were lymphatic bulges that were either in close contact with the base of the thick mesothelial cells or exposed through the mesothelial pores. The lymphatic network was especially well developed in the submesothelial layer at and around the thick-cell regions. The initial lymphatics drained into the intercostal collecting lymphatics, which in turn led into either the parasternal or paravertebral lymphatic trunk. Our results suggest that the stomata play a major role in absorbing fluids and particulates in the pleural cavity. The thick mesothelial cells

  9. Elevated CSF outflow resistance associated with impaired lymphatic CSF absorption in a rat model of kaolin-induced communicating hydrocephalus

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    Li Jie

    2010-02-01

    Full Text Available Abstract Background We recently reported a lymphatic cerebrospinal fluid (CSF absorption deficit in a kaolin model of communicating hydrocephalus in rats with ventricular expansion correlating negatively with the magnitude of the impediment to lymphatic function. However, it is possible that CSF drainage was not significantly altered if absorption at other sites compensated for the lymphatic defect. The purpose of this study was to investigate the impact of the lymphatic absorption deficit on global CSF absorption (CSF outflow resistance. Methods Kaolin was injected into the basal cisterns of Sprague Dawley rats. The development of hydrocephalus was assessed using magnetic resonance imaging (MRI. In one group of animals at about 3 weeks after injection, the movement of intraventricularly injected iodinated human serum albumin (125I-HSA into the olfactory turbinates provided an estimate of CSF transport through the cribriform plate into nasal lymphatics (n = 18. Control animals received saline in place of kaolin (n = 10. In a second group at about 3.5 weeks after kaolin injection, intraventricular pressure was measured continuously during infusion of saline into the spinal subarachnoid space at various flow rates (n = 9. CSF outflow resistance was calculated as the slope of the steady-state pressure versus flow rate. Control animals for this group either received no injections (intact: n = 11 or received saline in place of kaolin (n = 8. Results Compared to saline injected controls, lateral ventricular volume in the kaolin group was significantly greater (0.087 ± 0.013 ml, n = 27 versus 0.015 ± 0.001 ml, n = 17 and lymphatic function was significantly less (2.14 ± 0.72% injected/g, n = 18 versus 6.38 ± 0.60% injected/g, n = 10. Additionally, the CSF outflow resistance was significantly greater in the kaolin group (0.46 ± 0.04 cm H2O.μL-1.min, n = 9 than in saline injected (0.28 ± 0.03 cm H2O.μL-1.min, n = 8 or intact animals (0.18 ± 0

  10. Nonneoplastic Tongue Swellings of Lymphatic and Lymphocytic Origin: Three Case Reports

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    Manar A. Abdul Aziz

    2016-01-01

    Full Text Available Tongue is formed of a mass of muscles and salivary gland embedded in anterior highly vascular and posterior lymphoid stroma and covered by specialized surface epithelium. Growths from all of these heterogonous components may occur resulting in a wide variation in clinical features and behavior, ranging from self-limiting to aggressive lesions. Therefore, surgical excision is the treatment of choice. The aim of the current study is to report three different lesions that came to the Oral Surgery Department in the Faculty of Oral and Dental Medicine, Cairo University. Following clinical and histopathological examination, the diagnosis of reactive lymphoproliferative lesion, cystic lymphoepithelial lesion, and developmental lymphatic vessel malformation was reached.

  11. Development of a Mechanically Tuneable 3D Scaffold for Vascular Reconstruction

    Science.gov (United States)

    Rodriguez, Maritza; Juran, Cassandra; McClendon, Mark; Eyadiel, Cyril; McFetridge, Peter

    2012-01-01

    Material compliance has been shown to be a predictor of vascular graft patency and as such is a critical parameter when designing new materials. While ex vivo derived materials have been clinically successful in a number of applications their mechanical properties are a direct function of the original vessel and are not easily controllable. These investigations describe an approach to modulate the mechanical properties of an ex vivo derived scaffold by machining variable (discrete) wall thicknesses to control compliance. Human umbilical arteries (HUA) were machine-lathed directly from the umbilical cord at wall thicknesses of 250, 500, 750, and 1000 μm then decellularized using 1 % sodium dodecyl sulfate (SDS). Compliance over physiological pressures, increased from 3.08±1.84% to 11.47±4.11% as direct function of each discrete vessel diameter. Radial stress strain analysis revealed primary and secondary failure points attributed to the discrete layers within the anisotropic scaffold. Maximum strength and suture retention were shown to increase with increasing wall thickness, by contrast stress failure decreased with increasing thickness due to increasing proportions of the mechanically weaker amorphous Wharton’s jelly (WJ). Reseeded smooth muscle cells were shown to adhere, proliferate, and migrate from the scaffold surface showing the potential of the HUA as a mechanically ‘tunable’ material with applications as an acellular implant or as a tissue engineered construct. PMID:22826192

  12. Genetic Fingerprint Concerned with Lymphatic Metastasis of Human Lung Squamous Cancer

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    Xiaolong ZHAO

    2009-09-01

    Full Text Available Background and objective With the most recent introduction of microarray technology to biology, it becomes possible to perform comprehensive analysis of gene expression in cancer cell. In this study the laser microdissection technique and cDNA microarray analysis were combined to obtain accurate molecular profiles of lymphatic metastasis in patients with lung squamous cell carcinoma. Methods Primary lung squamous cancer tissues and regional lymph nodes were obtained from 10 patients who underwent complete resection of lung cancer. According to the source of lung cancer cells, the samples were classified into three groups: the primary tumor with lymphatic metastasis (TxN+, n=5, the primary tumor without lymphatic metastasis (TxN-, n=5 and matched tumor cells from metastatic lymph nodes (N+, n=5. Total RNA was extracted from laser microdissected tumor samples. Adequate RNA starting material of mRNA from primary tumor or metastatic nodes were labeled and then hybridized into the same microarray containing 6 000 known, named human genes/ESTs. After scanning, data analysis was performed using GeneSpringTM6.2. Results A total of 37 genes were found to be able to separate TxN+ from TxN-. TxN+ have higher levels of genes concerned with structural protein, signal transducer, chaperone and enzyme. TxN- have higher levels of genes coding for cell cycle regulator, transporter, signal transducer and apoptosis regulator. Interestingly, there were no differentially expressed genes between N+ and TxN+. Conclusion The acquisition of the metastatic phenotype might occur early in the development of lung squamous cancer. We raise the hypothesis that the gene-expression signature described herein is valuable to elucidate the molecular mechanisms regarding lymphatic metastasis and to look for novel therapeutic targets.

  13. Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.

    Science.gov (United States)

    Bakker, Erik N T P; Bacskai, Brian J; Arbel-Ornath, Michal; Aldea, Roxana; Bedussi, Beatrice; Morris, Alan W J; Weller, Roy O; Carare, Roxana O

    2016-03-01

    The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Aβ). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer's disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that Aβ is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of Aβ in the glia limitans in Alzheimer's disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of Aβ. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance.

  14. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van

    2004-01-01

    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  15. Morbidity trends in Lymphatic Filariasis: Analysis from a tertiary care center in Kerala, Southern India

    Directory of Open Access Journals (Sweden)

    Sushma Krishna

    2012-03-01

    Full Text Available Lymphatic filariasis in India contributes to nearly 40% of the global endemic burden. There is paucity of data regarding the association of chronic lymphatic filariasis with diabetes, coronary heart disease and other comorbidities. Case records over a period of ten years from 2001-2010 were reviewed and 113 diagnosed chronic filariasis cases from 13 districts of the state were identified.Prevalence of each of the morbidity with age and sex association was calculated. A total of 82(72.6% of them were in the age group of 60-85 years. Hypertension was noted in 48, type II diabetes in 46 and coronary artery disease in 43. Filariasis had a significant association with type II diabetes mellitus and coronary artery disease (p value< 0.05. Secondary infection. of leg ranging from cellulitis to gangrene was seen in 33(29.2%. Lymphatic Filariasis may be linked as an inclining factor for the development of type II diabetes mellitus and coronary heart disease over 60 years. Secondary leg infections continue in diabetic patients. The immuno- modulatory mechanisms involved needs to be explored.

  16. Cryotherapy for massive vulvar lymphatic leakage complicated with lymphangiomas following gynecological cancer treatment.

    Science.gov (United States)

    Yanazume, Shintaro; Douzono, Haruhiko; Kubo, Hidemichi; Nagata, Tomomi; Douchi, Tsutomu; Kobayashi, Hiroaki

    2014-11-01

    Vulvar lymphatic leakage is a severe complication associated with gynecological cancer treatments. However, standard treatment strategies have not yet been determined. We encountered a rare case of a 76-year-old multiparous woman suffering from massive lymphatic fluid leakage from the entire vulva, and papules developed and were identified as lymphangiomas. A large amount of straw-colored discharge continued from all vulvar papules, which extended over the mons pubis. Nine years ago, the patient had undergone a radical hysterectomy with concurrent chemoradiation for uterine cervical cancer treatment. Her serum albumin level was 1.9 mg/dl, which was attributed to the loss of a large amount of lymph fluid due to leakage from the vulva. Her quality of life gradually decreased because of general fatigue and the need for frequent diaper exchanges every 2 h. The patient received a less-invasive treatment with cryotherapy using liquid nitrogen. She also received a multimodality treatment consisting of the intravenous administration of albumin, massage of the lower limbs and intensive rehabilitation. Cryotherapy was administered once a week for 3 months. Her discharge almost stopped and vulvar lymphangiomas decreased without any major complications. To the best of our knowledge, this is the first case report of massive lymphatic leakage complicated with vulvar lymphangiomas. Additionally, this case may represent the first successful treatment of vulva lymph leakage by cryotherapy without recurrence. Cryotherapy may have the potential to improve the quality of life as a less-invasive treatment for gynecological cancer survivors without serious complications.

  17. Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema

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    Martínez Helena

    2011-03-01

    Full Text Available Abstract Background Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. Methods A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garnments. The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment. The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less atractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image. Discussion The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. Trial registration ClinicalTrials (NCT: NCT01152099

  18. Somatic component of risk of the development of vegetative-vascular dysfunction at children of the average and advanced school age

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    Olena Savchuk

    2016-10-01

    Full Text Available Purpose: to estimate quantitatively factors of somatic component of risk of the development of vegetative-vascular dysfunction at children of the average and advanced school age. Material & Methods: 569 children of 14–17 years old are examined in order to the existence of somatopathies, violation of posture, level and harmony of physical development, extent of development of adipopexis, functional indicators of health. Influence of somatic factors on risk of developing of vegetative-vascular dysfunction was revealed by means of the correlation analysis. Results: the system of assessment and the integrated indicator of action of somatic factors on risk of the development of vegetative-vascular dysfunction are offered. 6,57% of pupils with the low level of probability of risk of developing of vegetative-vascular dysfunction, 24,25% of pupils with the level below the average, 38,36% of children of 14–17 years old with the average level of probability of risk of developing of vegetative-vascular dysfunction, 24,25% of teenagers with the average level of probability, 6,57% of pupils with the high level of probability of risk of developing of vegetative-vascular dysfunction are revealed. The reliable communications between the low level of functionality on the test of Ruffier and the disharmonious physical development (p<0,001, low indicators of power and respiratory indexes (p<0,05 are established statistically. Conclusions: the children of the group of risk, who need the individual approach at lessons of physical culture, are defined.

  19. Design of lipid-based delivery systems for improving lymphatic transport and bioavailability of delta-tocopherol and nobiletin

    Science.gov (United States)

    Xia, Chunxin

    Lymphatic drug transport can confer bioavailability advantage by avoiding the first-pass metabolism normally observed in the portal vein hepatic route. It was reported that long chain lipid-based delivery systems can stimulate the formation of chylomicron and thus promote the lymphatic transport of drugs. In this study, a novel delta-tocopherol (delta-T) loaded Solid Lipid Nanoparticle (SLN) system was developed to investigate its effect on promoting the lymphatic transport of delta-T. The delta-T SLN was prepared with hot melt emulsification method by using glyceryl behenate (compritol RTM888) as the lipid phase and lecithin (PC75) as the emulsifier. Formula configuration, processing condition and loading capacity were carefully optimized. Physicochemical properties (particle size, surface charge, morphology) were also characterized. Moreover, excellent stability of the developed delta-T SLN in the gastrointestinal environment was observed by using an in vitro digestion model. Further investigations of the SLN in stimulating delta-T lymphatic transport were performed on mice without cannulation. Compared with the control group (delta-T corn oil dispersion), much lower delta-T levels in both blood and liver indicated reduced portal vein and hepatic transport of delta-T in the form of SLN. On the other hand, significantly higher concentrations of delta-T were observed in thymus, a major lymphatic tissue, indicating improved lymphatic transport of delta-T with the SLN delivery system. Finally, the far less excreted delta-T level in feces further confirmed improved lymphatic transport and overall bioavailability of delta-T by using SLN system. Nobiletin (NOB), one of most abundant polymethoxyflavones (PMFs) found in Citrus genus, has a low solubility in both water and oil at ambient temperatures. Thus it tends to form crystals when the loading exceeds its saturation level in the carrier system. This character greatly impaired its bioavailability and application. To

  20. High relative density of lymphatic vessels predicts poor survival in tongue squamous cell carcinoma.

    Science.gov (United States)

    Seppälä, Miia; Pohjola, Konsta; Laranne, Jussi; Rautiainen, Markus; Huhtala, Heini; Renkonen, Risto; Lemström, Karl; Paavonen, Timo; Toppila-Salmi, Sanna

    2016-12-01

    Tongue cancer has a poor prognosis due to its early metastasis via lymphatic vessels. The present study aimed at evaluating lymphatic vessel density, relative density of lymphatic vessel, and diameter of lymphatic vessels and its predictive role in tongue cancer. Paraffin-embedded tongue and lymph node specimens (n = 113) were stained immunohistochemically with a polyclonal antibody von Willebrand factor, recognizing blood and lymphatic endothelium and with a monoclonal antibody podoplanin, recognizing lymphatic endothelium. The relative density of lymphatic vessels was counted by dividing the mean number of lymphatic vessels per microscopic field (podoplanin) by the mean number of all vessels (vWf) per microscopic field. The high relative density of lymphatic vessels (≥80 %) was associated with poor prognosis in tongue cancer. The relative density of lymphatic vessels predicted poor prognosis in the group of primary tumor size T1-T2 and in the group of non-metastatic cancer. The lymphatic vessel density and diameter of lymphatic vessels were not associated with tongue cancer survival. The relative density of lymphatic vessels might have clinically relevant prognostic impact. Further studies with increased number of patients are needed.

  1. Structural and functional features of central nervous system lymphatic vessels.

    Science.gov (United States)

    Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

    2015-07-16

    One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

  2. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    Directory of Open Access Journals (Sweden)

    Brown Allison

    2008-01-01

    Full Text Available Abstract Background High tumour interstitial fluid pressure (IFP has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. Methods KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m, sub-cutaneously (s/c or orthotopically. Polyoma middle-T (MMTV-PyMT transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Results Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion

  3. Vascular rings.

    Science.gov (United States)

    Backer, Carl L; Mongé, Michael C; Popescu, Andrada R; Eltayeb, Osama M; Rastatter, Jeffrey C; Rigsby, Cynthia K

    2016-06-01

    The term vascular ring refers to congenital vascular anomalies of the aortic arch system that compress the esophagus and trachea, causing symptoms related to those two structures. The most common vascular rings are double aortic arch and right aortic arch with left ligamentum. Pulmonary artery sling is rare and these patients need to be carefully evaluated for frequently associated tracheal stenosis. Another cause of tracheal compression occurring only in infants is the innominate artery compression syndrome. In the current era, the diagnosis of a vascular ring is best established by CT imaging that can accurately delineate the anatomy of the vascular ring and associated tracheal pathology. For patients with a right aortic arch there recently has been an increased recognition of a structure called a Kommerell diverticulum which may require resection and transfer of the left subclavian artery to the left carotid artery. A very rare vascular ring is the circumflex aorta that is now treated with the aortic uncrossing operation. Patients with vascular rings should all have an echocardiogram because of the incidence of associated congenital heart disease. We also recommend bronchoscopy to assess for additional tracheal pathology and provide an assessment of the degree of tracheomalacia and bronchomalacia. The outcomes of surgical intervention are excellent and most patients have complete resolution of symptoms over a period of time. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Development and use of sulodexide in vascular diseases: implications for treatment

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    Coccheri S

    2013-12-01

    Full Text Available Sergio Coccheri,1 Ferdinando Mannello2 1Cardiovascular Medicine, University of Bologna, Bologna, 2Department of Biomolecular Sciences (Section Clinical Biochemistry and Cell Biology, University 'Carlo Bo', Urbino, Italy Abstract: Sulodexide (SDX, a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG entities, namely a fast-moving heparin (HP fraction and a dermatan sulfate (DS; 20% component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium. For this reason, in preclinical studies, SDX administered parenterally displays an antithrombotic action similar to that of HPs but associated with fewer alterations of the blood clotting mechanisms and tests, thus being much less conducive to bleeding risk than HPs. When given orally, SDX is associated with minimal changes in classic coagulation tests, but maintains a number of important effects on the structure and function of endothelial cells (EC, and the intercellular matrix. These activities include prevention or restoration of the integrity and permeability of EC, counteraction versus chemical, toxic or metabolic EC injury, regulation of EC–blood cell interactions, inhibition of microvascular inflammatory and proliferative changes, and other similar effects, thus allowing oral SDX to be considered as an endothelial-protecting agent. The best available clinical evidence of the efficacy of SDX administered orally with or without an initial parenteral phase is the following: alleviation of symptoms in chronic venous disease and especially acceleration of healing of venous leg ulcers; prevention of cardiovascular events in survivors after acute myocardial infarction; marked improvement of intermittent claudication in patients with peripheral occlusive arterial disease; and

  5. A comparison of retroperitoneoscopic and open surgical renal pedicle lymphatic disconnection for the treatment of serious filarial chyluria

    Institute of Scientific and Technical Information of China (English)

    LAN Wei-hua; JIN Feng-shuo; WANG Luo-fu; ZHU Fang-qiang

    2007-01-01

    @@ Currently the most effective clinical management for serious intractable chyluria is renal pedicle lymphatic disconnection, which generally consists of nephrolympholysis, renal hilar lymphatic vessel stripping and ureterolympholysis.

  6. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses.

    Directory of Open Access Journals (Sweden)

    Kimberly L Jordan-Williams

    Full Text Available Lymphocyte- and leukocyte-mediated lymph node (LN lymphatic sinus growth (lymphangiogenesis is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses.

  7. ACKR2: An Atypical Chemokine Receptor Regulating Lymphatic Biology

    Science.gov (United States)

    Bonavita, Ornella; Mollica Poeta, Valeria; Setten, Elisa; Massara, Matteo; Bonecchi, Raffaella

    2017-01-01

    The lymphatic system plays an important role in the induction of the immune response by transporting antigens, inflammatory mediators, and leukocytes from peripheral tissues to draining lymph nodes. It is emerging that lymphatic endothelial cells (LECs) are playing an active role in this context via the expression of chemokines, inflammatory mediators promoting cell migration, and chemokine receptors. Particularly, LECs express atypical chemokine receptors (ACKRs), which are unable to promote conventional signaling and cell migration while they are involved in the regulation of chemokine availability. Here, we provide a summary of the data on the role of ACKR2 expressed by lymphatics, indicating an essential role for this ACKRs in the regulation of the inflammation and the immune response in different pathological conditions, including infection, allergy, and cancer. PMID:28123388

  8. Study of fluid dynamics reveals direct communications between lymphatic vessels and venous blood vessels at lymph nodes of mice.

    Science.gov (United States)

    Takeda, Kazu; Mori, Shiro; Kodama, Tetsuya

    2017-02-22

    Cancer cells metastasize to lymph nodes, with distant metastasis resulting in poor prognosis. The role of lymph node metastasis (LNM) in the spread of cancer to distant organs remain incompletely characterized. The visualization of flow dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10mm in diameter, has revealed that lymph nodes have the potential to be a direct source of systemic metastasis. However, it is not known whether these fluid dynamics characteristics are universal phenomena present in other strains of laboratory mice. Here we show that the fluid dynamics observed in MXH10/Mo-lpr/lpr mice are the same as those observed in C57BL/6J, BALB/cAJcl and NOD/ShiJic-scidJcl mice. Furthermore, when fluorescent solution was injected into a tumor-bearing lymph node, the flow dynamics observed in the efferent lymphatic vessels and thoracoepigastric vein depended on the type of tumor cell. Our results indicate that fluid dynamics in the lymphatic and blood vessels of MXH10/Mo-lpr/lpr mice are generalized phenomena seen in conventional laboratory mice. We anticipate our results can facilitate studies of the progression of lymphatic metastasis to hematogenous metastasis via lymph nodes and the early diagnosis and treatment of LNM.

  9. VASCULAR SURGERY

    African Journals Online (AJOL)

    Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are linked to an increased risk of PE.2 .... tool for DVT in hospitalised patients, where higher scores.

  10. Vascular Dementia

    Science.gov (United States)

    ... that includes enjoyable activities well within the comfort zone of the person with vascular dementia. New situations, ... your cholesterol in check. A healthy, low-fat diet and cholesterol-lowering medications if you need them ...

  11. Expression and Suppressive Effects of Interleukin-19 on Vascular Smooth Muscle Cell Pathophysiology and Development of Intimal Hyperplasia

    Science.gov (United States)

    Tian, Ying; Sommerville, Laura J.; Cuneo, Anthony; Kelemen, Sheri E.; Autieri, Michael V.

    2008-01-01

    Anti-inflammatory cytokines may play a protective role in the progression of vascular disease. The purpose of this study was to characterize interleukin (IL)-19 expression and function in the development of intimal hyperplasia, and discern a potential mechanism of its direct effects on vascular smooth muscle cells (VSMCs). IL-19 is an immunomodulatory cytokine, the expression of which is reported to be restricted to inflammatory cells. In the present study, we found that IL-19 is not expressed in quiescent VSMCs or normal arteries but is induced in human arteries by injury and in cultured human VSMCs by inflammatory cytokines. Recombinant IL-19 significantly reduced VSMC proliferation (37.1 ± 4.8 × 103 versus 72.2 ± 6.1 × 103 cells/cm2) in a dose-dependent manner. IL-19 adenoviral gene transfer significantly reduced proliferation and neointimal formation in balloon angioplasty-injured rat carotid arteries (0.172 ± 29.9, versus 0.333 ± 71.9, and 0.309 ± 56.6 μm2). IL-19 induced activation of STAT3 as well as the expression of the suppressor of cytokine signaling 5 (SOCS5) in VSMCs. IL-19 treatment significantly reduced the activation of p44/42 and p38 MAPKs in stimulated VSMCs. Additionally, SOCS5 was found to interact with both p44/42 and p38 MAPKs in IL-19-treated human VSMCs. This is the first description of the expression of both IL-19 and SOCS5 in VSMCs and of the functional interaction between SOCS5 and MAPKs. We propose that through induction of SOCS5 and inhibition of signal transduction, IL-19 expression in VSMCs may represent a novel, protective, autocrine response of VSMCs to inflammatory stimuli. PMID:18669613

  12. Topography of Lymphatic Markers in Human Iris and Ciliary Body.

    Science.gov (United States)

    Kaser-Eichberger, Alexandra; Schrödl, Falk; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Motloch, Karolina; Bruckner, Daniela; Laimer, Martin; Schlereth, Simona L; Heindl, Ludwig M; Reitsamer, Herbert A

    2015-07-01

    Reports of lymphatics in the anterior human uvea are contradictory. This might be caused due to a certain topography, which has not been considered yet. Therefore, here we systematically analyze iris and adjacent ciliary body with immunohistochemistry by combining various lymphatic markers. Human iris and ciliary body were obtained from cornea donors and prepared for cryosectioning. Cross sections of tissue blocks at 12/3/6/9 o'clock position and at corresponding intersections (1:30/4:30/7:30/10:30) were processed for immunohistochemistry of LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, and CCL21, and when necessary, these lymphatic markers were combined with CD31, α-smooth muscle-actin, CD68, and 4',6-diamidino-2 phenylindole dihydrochloride (DAPI). Double, triple, and quadruple marker combinations were documented using confocal microscopy. Numerous podoplanin+ cells were mainly located at the anterior border of the iris while LYVE-1+ cells were distributed throughout the nonpigmented part. Both cell populations were PROX1/FOXC2/CCL21/VEGFR3-. Blood vessels, iris smooth muscles, and individual cells were VEGFR3+. While PDPN+ cells were rarely detected posteriorly of the iris root, many LYVE-1+ cells were present within the ciliary body muscle and villi. Within the muscle, occasionally PDPN+ vessel-like structures were detectable, but these were never colocalized with LYVE-1. Similar vessel-like structures were VEGFR3+/PROX1-/CCL21-, but CD31+. Further, ciliary muscle fibers and ciliary epithelium were immunoreactive for VEGFR3/CCL21, but were LYVE-1/PDPN-. A certain topography of structures at the various uvea-positions investigated was not obvious. The majority of LYVE-1+ cells displayed immunoreactivity for CD68. Lymphatic vessels colocalizing for at least two lymphatic markers were not detectable. Therefore, if present, putative lymphatic channels of the anterior uvea might display a different marker panel than generally presumed.

  13. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  14. vascular hemiplegia

    OpenAIRE

    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  15. Nuclear receptor subfamily 2 group F member 1a (nr2f1a is required for vascular development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Bao-Jueng Wu

    Full Text Available Genetic regulators and signaling pathways are important for the formation of blood vessels. Transcription factors controlling vein identity, intersegmental vessels (ISV growth and caudal vein plexus (CVP formation in zebrafish are little understood as yet. Here, we show the importance of the nuclear receptor subfamily member 1A (nr2f1a in zebrafish vascular development. Amino acid sequence alignment and phylogenetic analysis of nr2f1a is highly conserved among the vertebrates. Our in situ hybridization results showed nr2f1a mRNA is expressed in the lateral plate mesoderm at 18 somite stage and in vessels at 24-30 hpf, suggesting its roles in vasculization. Consistent with this morpholino-based knockdown of nr2fla impaired ISV growth and failed to develop fenestrated vascular structure in CVP, suggesting that nr2f1a has important roles in controlling ISV and CVP growth. Consequently, nr2f1a morphants showed pericardial edema and circulation defects. We further demonstrated reduced ISV cells and decreased CVP endothelial cells sprouting in nr2f1a morphants, indicating the growth impairment of ISV and CVP is due to a decrease of cell proliferation and migration, but not results from cell death in endothelial cells after morpholino knockdown. To test molecular mechanisms and signals that are associated with nr2f1a, we examined the expression of vascular markers. We found that a loss of nr2f1a results in a decreased expression of vein/ISV specific markers, flt4, mrc1, vascular markers stabilin and ephrinb2. This indicates the regulatory role of nr2f1a in controlling vascular development. We further showed that nr2f1a likely interact with Notch signaling by examining nr2f1a expression in rbpsuh morphants and DAPT-treatment embryos. Together, we show nr2f1a plays a critical role for vascular development in zebrafish.

  16. The ETS Factor, ETV2: a Master Regulator for Vascular Endothelial Cell Development.

    Science.gov (United States)

    Oh, Se-Yeong; Kim, Ju Young; Park, Changwon

    2015-12-01

    Appropriate vessel development and its coordinated function is essential for proper embryogenesis and homeostasis in the adult. Defects in vessels cause birth defects and are an important etiology of diseases such as cardiovascular disease, tumor and diabetes retinopathy. The accumulative data indicate that ETV2, an ETS transcription factor, performs a potent and indispensable function in mediating vessel development. This review discusses the recent progress of the study of ETV2 with special focus on its regulatory mechanisms and cell fate determining role in developing mouse embryos as well as somatic cells.

  17. Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods

    Directory of Open Access Journals (Sweden)

    Masayuki Nagahashi

    2016-12-01

    Conclusions: In agreement with the previous theory, our results confirm “S1P gradient” among blood, lymphatic fluid and peripheral lymphatic tissues. Convenient methods for collection and measurement of sphingolipids in lymphatic fluid are expected to provide new insights on functions of sphingolipids.

  18. Lack of functioning intratumoral lymphatics in colon and pancreas cancer tissue.

    Science.gov (United States)

    Olszewski, Waldemar L; Stanczyk, Marek; Gewartowska, Magdalena; Domaszewska-Szostek, Anna; Durlik, Marek

    2012-09-01

    There are controversial views as to whether intratumoral or peritumoral lymphatics play a dominant role in the metastatic process. Most clinical observations originate from studies of colon cancer. Colon contains mucosa and submucosa rich in lymphatics and with high lymph formation rate. This seems to be a prerequisite for easy metastasis of cancer cells to regional lymph nodes. However, there are other tissues as pancreas with a rudimentary lymphatic network where cancer metastasis formation is as intensive as in colon cancer. This contradicts the common notion that intratumor lymphatics play major role in metastases. We visualized interstitial space and lymphatics in the central and peripheral regions of colon and pancreas tumors using the color stereoscopic lymphography and simultaneously immunohistochemical performed stainings specific for lymphatic and blood endothelial cells. The density of open and compressed lymphatic and blood vessels was measured in the tumor core and edge. There were very few lymphatics in the colon and pancreas tumor core but numerous minor fluid "lakes" with no visible connection to the peritumoral lymphatics. Lining of "lakes" did not express molecular markers specific for lymphatic endothelial cells. Dense connective tissue surrounding tumor foci did not contain lymphatics. Peritumoral lymphatics were irregularly distributed in both types of tumor and only sporadically contained cells that might be tumor cells. Similar lymphoscintigraphic and histological pictures were seen in colon and pancreas cancer despite of different structure of both tissues. This suggests a uniform reaction of tissues to the growing cancer irrespective of the affected organ.

  19. Evaluation of lymphatic dysplasia in patients with congenital pleural effusion and ascites using indocyanine green lymphography.

    Science.gov (United States)

    Shibasaki, Jun; Hara, Hisako; Mihara, Makoto; Adachi, Shinya; Uchida, Yasushi; Itani, Yasufumi

    2014-05-01

    To investigate the use of indocyanine green (ICG) lymphography in the diagnosis and assessment of the severity of lymphatic dysfunction in infants and neonates with congenital lymphatic pleural effusion and ascites. We performed ICG lymphography on 10 neonates and infants with congenital lymphatic pleural effusion and ascites. After the subcutaneous injection of ICG, circumferential fluorescent images of lymphatic drainage channels in the extremities and trunk were identified using an infrared camera system. The lymphographic findings were classifiable into 2 patterns-those showing a linear lymphatic pattern, suggesting normal lymphatic flow, and those showing lymphatic channels with retrograde lymphatic flow (dermal backflow pattern), suggesting an abnormal lymphatic flow. We analyzed the severity of the ICG lymphography findings and the clinical outcomes. Based on the ICG lymphography, the severity of lymphatic dysplasia were classified into 4 categories: mild dysplasia, moderate dysplasia, severe dysplasia, and lymphatic hypoplasia. All cases diagnosed with mild (n = 3) or moderate dysplasia (n = 2) survived, and 2 of the 4 cases diagnosed with severe dysplasia died. The duration of endotracheal intubation ranged from 1 to 17 days (median, 7) in the patients with mild or moderate dysplasia and from 25 to 110 days (median, 77) in those with severe dysplasia. The ICG lymphographic findings were consistent with the clinical conditions. This imaging technique may be important to the future clinical management of lymphatic dysplasia in neonates and infants. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Transmission models and management of lymphatic filariasis elimination.

    Science.gov (United States)

    Michael, Edwin; Gambhir, Manoj

    2010-01-01

    The planning and evaluation of parasitic control programmes are complicated by the many interacting population dynamic and programmatic factors that determine infection trends under different control options. A key need is quantification about the status of the parasite system state at any one given timepoint and the dynamic change brought upon that state as an intervention program proceeds. Here, we focus on the control and elimination of the vector-borne disease, lymphatic filariasis, to show how mathematical models of parasite transmission can provide a quantitative framework for aiding the design of parasite elimination and monitoring programs by their ability to support (1) conducting rational analysis and definition of endpoints for different programmatic aims or objectives, including transmission endpoints for disease elimination, (2) undertaking strategic analysis to aid the optimal design of intervention programs to meet set endpoints under different endemic settings and (3) providing support for performing informed evaluations of ongoing programs, including aiding the formation of timely adaptive management strategies to correct for any observed deficiencies in program effectiveness. The results also highlight how the use of a model-based framework will be critical to addressing the impacts of ecological complexities, heterogeneities and uncertainties on effective parasite management and thereby guiding the development of strategies to resolve and overcome such real-world complexities. In particular, we underscore how this approach can provide a link between ecological science and policy by revealing novel tools and measures to appraise and enhance the biological controllability or eradicability of parasitic diseases. We conclude by emphasizing an urgent need to develop and apply flexible adaptive management frameworks informed by mathematical models that are based on learning and reducing uncertainty using monitoring data, apply phased or sequential

  1. Intragraft platelet-derived growth factor-alpha and transforming growth factor-beta1 during the development of accelerated graft vascular disease after clinical heart transplantation

    NARCIS (Netherlands)

    de Groot-Kruseman, H A; Baan, C C; Mol, W M; Niesters, H G; Maat, A P; Balk, A H; Weimar, W

    1999-01-01

    This study was to determine whether the growth factors platelet-derived growth factor-alpha (PDGF-alpha) and transforming growth factor-beta1 (TGF-beta1) contribute to the development of graft vascular disease (GVD) after clinical heart transplantation. We analysed intragraft PDGF-alpha and TGF-beta

  2. Self-management support program for patients with cardiovascular diseases: user-centered development of the tailored, web-based program vascular view.

    NARCIS (Netherlands)

    Puijk-Hekman, S.; Gaal, B.G.I. van; Bredie, S.J.; Nijhuis-van der Sanden M.W.G.; Dulmen, S. van

    2017-01-01

    Background: In addition to medical intervention and counseling, patients with cardiovascular disease (CVD) need to manage their disease and its consequences by themselves in daily life. Objective: The aim of this paper is to describe the development of “Vascular View,” a comprehensive, multi-compone

  3. Role of leptin signaling in hemato-vascular development and niche function: Leptin receptor-mediated signaling regulates LT-HSC homeostasis in vivo

    Science.gov (United States)

    Homeostatic functioning of the cardiovascular and hematopoietic systems is known to be interdependent and strongly influenced by the microenvironment in which hemato-vascular cells develop and reside. The role of nutrition and metabolism as regulable and dynamic extracellular cues however, remains a...

  4. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    OpenAIRE

    Guan, Jian; Guillermo, Rosamond B.; Yang, Panzao; Vickers, Mark H.; McJarrow, Paul

    2015-01-01

    Background: Supplementation with complex milk lipids (CML) during postnatal brain development has been shown to improve spatial reference learning in rats.Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory.Design: The study used the brain tissues from the rats (male Wistar, 80 days of age) after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistoche...

  5. Development of a System and Method for Automated Isolation of Stromal Vascular Fraction from Adipose Tissue Lipoaspirate

    Directory of Open Access Journals (Sweden)

    Swathi SundarRaj

    2015-01-01

    Full Text Available Autologous fat grafting for soft tissue reconstruction is challenged by unpredictable long-term graft survival. Fat derived stromal vascular fraction (SVF is gaining popularity in tissue reconstruction as SVF-enriched fat grafts demonstrate improved engraftment. SVF also has potential in regenerative medicine for remodeling of ischemic tissues by promoting angiogenesis. Since SVF cells do not require culture expansion, attempts are being made to develop automated devices to isolate SVF at the point of care. We report development of a closed, automated system to process up to 500 mL lipoaspirate using cell size-dependent filtration technology. The yield of SVF obtained by automated tissue digestion and filtration (1.17 ± 0.5 × 105 cells/gram was equivalent to that obtained by manual isolation (1.15 ± 0.3 × 105; p = 0.8, and the viability of the cells isolated by both methods was greater than 90%. Cell composition included CD34+CD31− adipose stromal cells, CD34+CD31+ endothelial progenitor cells, and CD34−CD31+ endothelial cells, and their relative percentages were equivalent to SVF isolated by the manual method. CFU-F capacity and expression of angiogenic factors were also comparable with the manual method, establishing proof-of-concept for fully automated SVF isolation, suitable for use in reconstructive surgeries and regenerative medicine applications.

  6. Large-scale screening of transcription factor-promoter interactions in spruce reveals a transcriptional network involved in vascular development.

    Science.gov (United States)

    Duval, Isabelle; Lachance, Denis; Giguère, Isabelle; Bomal, Claude; Morency, Marie-Josée; Pelletier, Gervais; Boyle, Brian; MacKay, John J; Séguin, Armand

    2014-06-01

    This research aimed to investigate the role of diverse transcription factors (TFs) and to delineate gene regulatory networks directly in conifers at a relatively high-throughput level. The approach integrated sequence analyses, transcript profiling, and development of a conifer-specific activation assay. Transcript accumulation profiles of 102 TFs and potential target genes were clustered to identify groups of coordinately expressed genes. Several different patterns of transcript accumulation were observed by profiling in nine different organs and tissues: 27 genes were preferential to secondary xylem both in stems and roots, and other genes were preferential to phelloderm and periderm or were more ubiquitous. A robust system has been established as a screening approach to define which TFs have the ability to regulate a given promoter in planta. Trans-activation or repression effects were observed in 30% of TF-candidate gene promoter combinations. As a proof of concept, phylogenetic analysis and expression and trans-activation data were used to demonstrate that two spruce NAC-domain proteins most likely play key roles in secondary vascular growth as observed in other plant species. This study tested many TFs from diverse families in a conifer tree species, which broadens the knowledge of promoter-TF interactions in wood development and enables comparisons of gene regulatory networks found in angiosperms and gymnosperms.

  7. Longitudinal MRI evaluation of intracranial development and vascular characteristics of breast cancer brain metastases in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heling Zhou

    Full Text Available Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34% of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03 than that of contralateral normal brain (mean= 1.00±0.03; p<0.005. Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05. The rCBV data were concordant with histological analysis of microvascular density (MVD. Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

  8. Molecular and cellular effects of in vitro shockwave treatment on lymphatic endothelial cells.

    Directory of Open Access Journals (Sweden)

    Sabrina Rohringer

    Full Text Available Extracorporeal shockwave treatment was shown to improve orthopaedic diseases and wound healing and to stimulate lymphangiogenesis in vivo. The aim of this study was to investigate in vitro shockwave treatment (IVSWT effects on lymphatic endothelial cell (LEC behavior and lymphangiogenesis. We analyzed migration, proliferation, vascular tube forming capability and marker expression changes of LECs after IVSWT compared with HUVECs. Finally, transcriptome- and miRNA analyses were conducted to gain deeper insight into the IVSWT-induced molecular mechanisms in LECs. The results indicate that IVSWT-mediated proliferation changes of LECs are highly energy flux density-dependent and LEC 2D as well as 3D migration was enhanced through IVSWT. IVSWT suppressed HUVEC 3D migration but enhanced vasculogenesis. Furthermore, we identified podoplaninhigh and podoplaninlow cell subpopulations, whose ratios changed upon IVSWT treatment. Transcriptome- and miRNA analyses on these populations showed differences in genes specific for signaling and vascular tissue. Our findings help to understand the cellular and molecular mechanisms underlying shockwave-induced lymphangiogenesis in vivo.

  9. hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

    Science.gov (United States)

    Schanz, Andrea; Lukosz, Margarete; Hess, Alexandra P; Baston-Büst, Dunja M; Krüssel, Jan S; Heiss, Christian

    2015-08-01

    Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

  10. National mass drug administration costs for lymphatic filariasis elimination.

    Directory of Open Access Journals (Sweden)

    Ann S Goldman

    Full Text Available BACKGROUND: Because lymphatic filariasis (LF elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin, a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. METHODOLOGY/PRINCIPAL FINDINGS: To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1 the total annual cost of the LF program, 2 the average cost per person treated, and 3 the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1 the age (newness of the MDA program, 2 the use of volunteers, and 3 the size of the population treated. Substantial contributions by governments were documented - generally 60%-90% of program operation costs, excluding costs of donated medications. CONCLUSIONS/SIGNIFICANCE: MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.

  11. Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation.

    Directory of Open Access Journals (Sweden)

    Akinori Sato

    Full Text Available Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema.

  12. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, N; Simonsen, L; Holst, Jens Juul

    2012-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

  13. [Hygienic evaluation of chronic lymphatic leukemia in Bashkortostan Republic].

    Science.gov (United States)

    Bakirov, B A; Varshavskiĭ, A V; Bakirov, A B

    2009-01-01

    Prevalence of chronic lymphatic leukemia increased in Bashkortostan Republic over 1999-2008 with predominance of urban population, male patients, individuals aged 80-84. Reliable correlation was seen between pollutants releases into the ambient air and the morbidity parameters over following 5 years.

  14. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    Science.gov (United States)

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.

  15. [THE STRUCTURE OF LYMPHATIC CAPILLARIES OF THE CILIARY BODY OF THE HUMAN EYE].

    Science.gov (United States)

    Borodin, Yu I; Bgatova, N P; Chernykh, V V; Trunov, A N; Pozhidayeva, A A; Konenkov, V I

    2015-01-01

    Using light microscopy, immunohistochemistry and electron microscopy, the structural organization of interstitial spaces and vessels of the ciliary body of the human eye (n = 5) were studied. The ciliary body was found to contain wide interstitial spaces--tissue clefts bound by collagen fibers and fibroblasts. Organ-specific lymphatic capillaries were also demonstrated in the ciliary body. According to the present findings and the lymphatic region concept, the first 2 elements of the lymphatic region of the eye were described: tissue clefts--prelymphatics and lymphatic capillaries of the ciliary body. The third element of the lymphatic region are the lymph nodes of the head and neck.

  16. An improvement of cerebral hemodynamics in a newly developed perfusion area evaluated by intra-arterial SPECT following vascular reconstructive surgery

    Energy Technology Data Exchange (ETDEWEB)

    Nochide, Ichiro [Ehime Univ., Shigenobu (Japan). School of Medicine

    1999-06-01

    The purpose of this study was to evaluate the changes in regional cerebral blood flow (rCBF) and vascular reserve ({Delta}CBF) responding to acetazolamide loading by {sup 133}Xe SPECT. In combination, this study assessed the newly developed region of cerebral perfusion via bypass arteries after surgical vascular reconstruction in 11 hemispheres of 11 patients with atherosclerotic arterial occlusive disease and adult onset moyamoya disease. In patients with atherosclerotic occlusive disease, the cerebral perfusion from bypass arteries mainly developed in the preoperatively low {Delta}CBF territory. Although rCBF did not significantly alter after vascular reconstruction, preoperatively low {Delta}CBF was significantly improved to the normal range in the promotion of postoperatively newly born perfusion from bypass arteries. In 21 hemispheres of 13 patients with adult onset moyamoya disease, the postoperatively newly born perfusion from bypass arteries was significantly developed in the regions with either preoperative low rCBF or low {Delta}CBF. Although both rCBF and {Delta}CBF were significantly improved after the operation, {Delta}CBF was not restored satisfactorily up to the normal range in contrast to the sufficient increase of rCBF, even where the perfusion from the bypass artery was observed after the reconstructive surgeries. Vascular reconstructive surgeries were beneficial for the improvement of {Delta}CBF in the atherosclerotic arterial occlusive disease and rCBF in the adult-onset moyamoya disease, respectively. (author)

  17. Developmental programming: the concept, large animal models, and the key role of uteroplacental vascular development.

    Science.gov (United States)

    Reynolds, L P; Borowicz, P P; Caton, J S; Vonnahme, K A; Luther, J S; Hammer, C J; Maddock Carlin, K R; Grazul-Bilska, A T; Redmer, D A

    2010-04-01

    Developmental programming refers to the programming of various bodily systems and processes by a stressor of the maternal system during pregnancy or during the neonatal period. Such stressors include nutritional stress, multiple pregnancy (i.e., increased numbers of fetuses in the gravid uterus), environmental stress (e.g., high environmental temperature, high altitude, prenatal steroid exposure), gynecological immaturity, and maternal or fetal genotype. Programming refers to impaired function of numerous bodily systems or processes, leading to poor growth, altered body composition, metabolic dysfunction, and poor productivity (e.g., poor growth, reproductive dysfunction) of the offspring throughout their lifespan and even across generations. A key component of developmental programming seems to be placental dysfunction, leading to altered fetal growth and development. We discuss various large animal models of developmental programming and how they have and will continue to contribute to our understanding of the mechanisms underlying altered placental function and developmental programming, and, further, how large animal models also will be critical to the identification and application of therapeutic strategies that will alleviate the negative consequences of developmental programming to improve offspring performance in livestock production and human medicine.

  18. Receptor mechanisms of PAF mediated lymphatic constriction in the canine forelimb

    Directory of Open Access Journals (Sweden)

    D. E. Dobbins

    1992-01-01

    Full Text Available Platelet activating factor (PAF is a potent inflammatory lipid. In this study we assessed the ability of PAF to impact lymphatic vessel function by altering prenodal lymphatic resistance. Intralymphatic PAF (7.47 × 10−6, 7.47 × 10−5 and 7.47 × 10−4 M increased lymphatic perfusion pressure at the two highest infusion rates. PAF mediated lymphatic constriction was not altered by the intra-arterial infusion of phentolamine but was blocked by the intra-arterial infusion of the PAF receptor antagonist WEB 2170. These data indicate that in addition to PAF's effects on microvascular permeability, this agent may also impact the ability of the lymphatics to transport fluid through alterations in lymphatic smooth muscle tone. PAF mediated lymphatic constriction is not mediated by α-receptors but rather through PAF receptor mediated mechanism.

  19. Mutations in Lama1 disrupt retinal vascular development and inner limiting membrane formation.

    Science.gov (United States)

    Edwards, Malia M; Mammadova-Bach, Elmina; Alpy, Fabien; Klein, Annick; Hicks, Wanda L; Roux, Michel; Simon-Assmann, Patricia; Smith, Richard S; Orend, Gertraud; Wu, Jiang; Peachey, Neal S; Naggert, Jürgen K; Lefebvre, Olivier; Nishina, Patsy M

    2010-03-05

    The Neuromutagenesis Facility at the Jackson Laboratory generated a mouse model of retinal vasculopathy, nmf223, which is characterized clinically by vitreal fibroplasia and vessel tortuosity. nmf223 homozygotes also have reduced electroretinogram responses, which are coupled histologically with a thinning of the inner nuclear layer. The nmf223 locus was mapped to chromosome 17, and a missense mutation was identified in Lama1 that leads to the substitution of cysteine for a tyrosine at amino acid 265 of laminin alpha1, a basement membrane protein. Despite normal localization of laminin alpha1 and other components of the inner limiting membrane, a reduced integrity of this structure was suggested by ectopic cells and blood vessels within the vitreous. Immunohistochemical characterization of nmf223 homozygous retinas demonstrated the abnormal migration of retinal astrocytes into the vitreous along with the persistence of hyaloid vasculature. The Y265C mutation significantly reduced laminin N-terminal domain (LN) interactions in a bacterial two-hybrid system. Therefore, this mutation could affect interactions between laminin alpha1 and other laminin chains. To expand upon these findings, a Lama1 null mutant, Lama1(tm1.1Olf), was generated that exhibits a similar but more severe retinal phenotype than that seen in nmf223 homozygotes. The increased severity of the Lama1 null mutant phenotype is probably due to the complete loss of the inner limiting membrane in these mice. This first report of viable Lama1 mouse mutants emphasizes the importance of this gene in retinal development. The data presented herein suggest that hypomorphic mutations in human LAMA1 could lead to retinal disease.

  20. Nitrogen mustard (Chlorambucil) has a negative influence on early vascular development.

    Science.gov (United States)

    Schmidt, Annette; Bölck, Birgit; Jedig, Maria; Steinritz, Dirk; Balszuweit, Frank; Kehe, Kai; Bloch, Wilhelm

    2009-09-01

    The sulphur and nitrogen mustards are strong alkylating agents, which induces inflammations of the skin including blistering right up to ulcerations. Depending on the severity, the wounds may need weeks to heal. In the past it was shown that sulphur mustard has a destructive effect on endothelial precursor cells, which have been shown to play a pivotal role in the wound healing reaction by inducing neovascularisation. However, for these alkylating agents as well as for sulphur mustard nothing is known about their effects on endothelial precursors. Therefore, we investigated and compared the influence of Chlorambucil on proliferation, apoptosis and differentiation of endothelial cells in intact mouse embryoid bodies (EB). EBs were treated at different developmental stages and with different periods of Chlorambucil treatment. It was found that in each developmental stage and under each treatment period's Chlorambucil has an extremely negative effect on the vascularisation with a vessel reduction of around 99%. Of particular importance was the negative effect of treatment around day 3 of the development. On this day we found 377 vessels under control conditions but only 1.6 vessels under 24h treatment of Chlorambucil. At this point in time many endothelial precursors can be found in the EB. Moreover, a negative effect on all stem cells was evident at this point in time, shown by an extreme reduction in EB size with 17.9 mm(2) for the control and only 1.55 mm(2) under Chlorambucil treatment. This negative effect on the vascularisation, on endothelial precursors but also on stem cells in general is of possible importance for impaired wound healing.

  1. Determinants of developing diabetes mellitus and vascular complications in patients with impaired fasting glucose

    Directory of Open Access Journals (Sweden)

    Faranak Sharifi

    2013-01-01

    Full Text Available Aims: To detect the risk factors of diabetes mellitus (DM and cardiovascular complications in subjects with impaired fasting glucose (IFG. Materials and Methods: One hundred and twenty three subjects with proved IFG in Zanjan Healthy Heart Study (2002-2003 were recalled and participated in this study (2009-2010. Demographic and laboratoryinformation of the participants were collected.Ischemic heart disease (IHD was assessed by the exercise tolerance test (ETT. All the subjects with abnormal ETT or documented past history of IHD confirmed by angiographic evaluation. Ophthalmic complications including cataract, glaucoma, and diabetic retinopathy were estimated by an ophthalmologist. Results: Incidence of DM was 19.5%. All the diabetic and pre-diabetic patients had at least one of the other components of metabolic syndrome. Obesity (P: 0.04, OR: 1.8, 95%CI: 1.2-9 and low physical activity (P < 0.001, OR: 9.6, 95%CI: 3.4-32 were the only independent prognostic risk factors for progression to DM in patients with IFG. Total incidence of IHD was 14.6% and had a strong correlation with sex (P: 0.01, OR: 1.8, 95%CI: 1.2-1.5, age (P < 0.001, OR: 23, 95%CI: 2.1-67 and cigarette smoking (P < 0.001, OR: 36.5, 95%CI: 3.9-337. Non-proliferative diabetic retinopathy was shown in 2 (1.6% subjects who were all women. Conclusion: Obesity and low physical activity are the main factors of developing DM and its macrovascular complications in subjects with IFG.

  2. Modelling Co-Infection with Malaria and Lymphatic Filariasis

    Science.gov (United States)

    Slater, Hannah C.; Gambhir, Manoj; Parham, Paul E.; Michael, Edwin

    2013-01-01

    Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change), and the associated timescale for such changes, as well as effects on the basic reproduction number R0 of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings. PMID:23785271

  3. Vascular emergencies.

    Science.gov (United States)

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  4. Vascular Disease Foundation

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  5. What Is Vascular Disease?

    Science.gov (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  6. The utility of GLUT1 as a diagnostic marker in cutaneous vascular anomalies: A review of literature and recommendations for daily practice.

    Science.gov (United States)

    van Vugt, Lieke J; van der Vleuten, Carine J M; Flucke, Uta; Blokx, Willeke A M

    2017-06-01

    To assess the utility of GLUT1 as an immunohistochemical marker in the diagnostics of cutaneous vascular anomalies. A systematic literature search was conducted for studies on GLUT1 staining patterns in cutaneous vascular lesions. Data was grouped according to the latest ISSVA classification for vascular anomalies. Vascular tumors: GLUT1 staining was positive in 368/386 (95%) of infantile hemangiomas. Congenital hemangiomas (16 cases) and kaposiform hemangioendotheliomas (62 cases) were all negative for GLUT1. Angiosarcomas were GLUT1 positive in 12/39 (31%) and epithelioid hemangioendotheliomas in 2/27 (7%) of cases. Vascular malformations: All vascular malformations (33 arteriovenous malformations, 16 capillary malformations, 64 lymphatic malformations, 54 venous malformations, 3 venous-lymphatic malformations and 3 capillary venous-lymphatic malformations) were negative for GLUT1 staining. Unclassified vascular anomalies: Angiokeratomas were GLUT1 positive in 1/15 (7%) and verrucous hemangiomas in 71/100 (71%) of cases. Microvenular hemangiomas were negative for GLUT1 in all 9 cases. GLUT1 can be used as an additional diagnostic tool in cutaneous vascular lesions. A negative GLUT1 stain renders a diagnosis of infantile hemangioma unlikely. A positive GLUT1 stain excludes vascular malformations and is suggestive of infantile hemangioma. One must be cautious, however, that the final diagnosis is made through interpretation of all clinical and diagnostic features, and not based on GLUT1 staining alone. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Vascular Canals in Permanent Hyaline Cartilage: Development, Corrosion of Nonmineralized Cartilage Matrix, and Removal of Matrix Degradation Products.

    Science.gov (United States)

    Gabner, Simone; Häusler, Gabriele; Böck, Peter

    2017-06-01

    Core areas in voluminous pieces of permanent cartilage are metabolically supplied via vascular canals (VCs). We studied cartilage corrosion and removal of matrix degradation products during the development of VCs in nose and rib cartilage of piglets. Conventional staining methods were used for glycosaminoglycans, immunohistochemistry was performed to demonstrate collagens types I and II, laminin, Ki-67, von Willebrand factor, VEGF, macrophage marker MAC387, S-100 protein, MMPs -2,-9,-13,-14, and their inhibitors TIMP1 and TIMP2. VCs derived from connective tissue buds that bulged into cartilage matrix ("perichondrial papillae", PPs). Matrix was corroded at the tips of PPs or resulting VCs. Connective tissue stromata in PPs and VCs comprised an axial afferent blood vessel, peripherally located wide capillaries, fibroblasts, newly synthesized matrix, and residues of corroded cartilage matrix (collagen type II, acidic proteoglycans). Multinucleated chondroclasts were absent, and monocytes/macrophages were not seen outside the blood vessels. Vanishing acidity characterized areas of extracellular matrix degradation ("preresorptive layers"), from where the dismantled matrix components diffused out. Leached-out material stained in an identical manner to intact cartilage matrix. It was detected in the stroma and inside capillaries and associated downstream veins. We conclude that the delicate VCs are excavated by endothelial sprouts and fibroblasts, whilst chondroclasts are specialized to remove high volumes of mineralized cartilage. VCs leading into permanent cartilage can be formed by corrosion or inclusion, but most VCs comprise segments that have developed in either of these ways. Anat Rec, 300:1067-1082, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

    Directory of Open Access Journals (Sweden)

    Mariella eErrede

    2014-10-01

    Full Text Available This study was conducted on human developing brain by laser confocal and transmission electron microscopy to make a detailed analysis of important features of blood-brain barrier microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The blood-brain barrier status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration and before cortex lamination, with blood-brain barrier-endothelial cell markers, namely tight junction proteins (occludin and claudin-5 and influx and efflux transporters (Glut-1 and P-glycoprotein, the latter supporting evidence for functional effectiveness of the fetal blood-brain barrier. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analysed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43 were utilized as markers of radial glia cells, CD105 (endoglin as a marker of angiogenically activated endothelial cells, and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial fibres in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical vessel-specific RG fibre swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of radial glial varicosities reveals colocalization of CXCL12 with connexin Cx43, which is possibly implicated in vessel-specific chemokine signalling.

  9. Urinary potassium excretion and risk of developing hypertension: the prevention of renal and vascular end-stage disease study.

    Science.gov (United States)

    Kieneker, Lyanne M; Gansevoort, Ron T; Mukamal, Kenneth J; de Boer, Rudolf A; Navis, Gerjan; Bakker, Stephan J L; Joosten, Michel M

    2014-10-01

    Previous prospective cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake, may provide a more objective and quantitative estimate of this association. Risk of hypertension (defined as blood pressure ≥140/90 mm Hg or initiation of blood pressure-lowering drugs) was prospectively studied in 5511 normotensive subjects aged 28 to 75 years not using blood pressure-lowering drugs at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Potassium excretion was measured in two 24-hour urine specimens at baseline (1997-1998) and midway during follow-up (2001-2003). Baseline median potassium excretion was 70 mmol/24 h (interquartile range, 57-85 mmol/24 h), which corresponds to a dietary potassium intake of ≈91 mmol/24 h. During a median follow-up of 7.6 years (interquartile range, 5.0-9.3 years), 1172 subjects developed hypertension. The lowest sex-specific tertile of potassium excretion (men: hypertension after multivariable adjustment (hazard ratio, 1.20; 95% confidence interval, 1.05-1.37), compared with the upper 2 tertiles (Pnonlinearity=0.008). The proportion of hypertension attributable to low potassium excretion was 6.2% (95% confidence interval, 1.7%-10.9%). No association was found between the sodium to potassium excretion ratio and risk of hypertension after multivariable adjustment. Low urinary potassium excretion was associated with an increased risk of developing hypertension. Dietary strategies to increase potassium intake to the recommended level of 90 mmol/d may have the potential to reduce the incidence of hypertension.

  10. The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.

    Science.gov (United States)

    Ramachandran, Sabarinathan; Kumar, Mishra Pankaj; Rami, Reddy Maryada Venkata; Chinnaiah, Harinath Basker; Nutman, Thomas; Kaliraj, Perumal; McCarthy, James

    2004-01-01

    Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.

  11. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Renata Mężyk-Kopeć

    Full Text Available Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC. When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i single-cell motility, (ii cell migration through a 3D Matrigel/collagen type I matrix, and (iii their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  12. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    Science.gov (United States)

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  13. The vascular surgeon-scientist: a 15-year report of the Society for Vascular Surgery Foundation/National Heart, Lung, and Blood Institute-mentored Career Development Award Program.

    Science.gov (United States)

    Kibbe, Melina R; Dardik, Alan; Velazquez, Omaida C; Conte, Michael S

    2015-04-01

    The Society for Vascular Surgery (SVS) Foundation partnered with the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) in 1999 to initiate a competitive career development program that provides a financial supplement to surgeon-scientists receiving NIH K08 or K23 career development awards. Because the program has been in existence for 15 years, a review of the program's success has been performed. Between 1999 and 2013, 41 faculty members applied to the SVS Foundation program, and 29 from 21 different institutions were selected as awardees, resulting in a 71% success rate. Three women (10%) were among the 29 awardees. Nine awardees (31%) were supported by prior NIH F32 or T32 training grants. Awardees received their K award at an average of 3.5 years from the start of their faculty position, at the average age of 39.8 years. Thirteen awardees (45%) have subsequently received NIH R01 awards and five (17%) have received Veterans Affairs Merit Awards. Awardees received their first R01 at an average of 5.8 years after the start of their K award at the average age of 45.2 years. The SVS Foundation committed $9,350,000 to the Career Development Award Program. Awardees subsequently secured $45,108,174 in NIH and Veterans Affairs funds, resulting in a 4.8-fold financial return on investment for the SVS Foundation program. Overall, 23 awardees (79%) were promoted from assistant to associate professor in an average of 5.9 years, and 10 (34%) were promoted from associate professor to professor in an average of 5.2 years. Six awardees (21%) hold endowed professorships and four (14%) have secured tenure. Many of the awardees hold positions of leadership, including 12 (41%) as division chief and two (7%) as vice chair within a department of surgery. Eight (28%) awardees have served as president of a regional or national society. Lastly, 47 postdoctoral trainees have been mentored by recipients of the SVS Foundation Career Development

  14. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  15. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  16. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    Energy Technology Data Exchange (ETDEWEB)

    Yan Zhiqiang; Zhan Changyou; Wen Ziyi; Feng Linglin; Wang Fei; Liu Yu; Yang Xiangkun; Dong Qing; Liu Min; Lu Weiyue, E-mail: wylu@shmu.edu.cn [Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203 (China)

    2011-10-14

    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  17. Mast cells in common wolffish Anarhichas lupus L.: ontogeny, distribution and association with lymphatic vessels.

    Science.gov (United States)

    Hellberg, Hege; Bjerkås, Inge; Vågnes, Øyvind B; Noga, Edward J

    2013-12-01

    The morphology, ontogeny and tissue distribution of mast cells were studied in common wolffish(Anarhichas lupus L.) at the larval, juvenile and adult life stages using light and electron-microscopy and immunohistochemistry. Fish were sampled at 1 day, 1, 2, 3, 4, 8 and 12 weeks post-hatching in addition to 6 and 9 months and 2 years and older. From 8 weeks post-hatching, mast cells in common wolffish mainly appeared as oval or rounded cells 8-15 mm in diameter with an eccentrically placed, ovoid nucleus and filled with cytoplasmic granules up to 1.2 mm in diameter. Granules were refractile and eosinophilic to slightly basophilic in H&E and stained bright red with Martius-scarlet-blue and purple with pinacyanol erythrosinate in formalin-fixed tissues. Mast cells stained positive for piscidin 4 and Fc ε RI by immunohistochemistry. From 1 day to 4 weeks post-hatching, immature mast cell containing only a few irregularly sized cytoplasmic granules were observed by light and electron-microscopy in loose connective tissue of cranial areas. From 1 day post-hatching, these cells stained positive for piscidin 4 and Fc ε RI by immunohistochemistry. From 12 weeks post-hatching, mast cells showed a primarily perivascular distribution and were particularly closely associated with lymphatic vessels and sinuses. Mast cells were mainly located at the peripheral border of the adventitia of arteries and veins, while they were in intimate contact with the endothelium of the lymphatic vessels. Numerous mast cells were observed in the intestine. A stratum compactum, as described in salmonids, was not observed in wolffish intestine,nor were mast cells confined to a separate layer, a stratum granulosum. Lymphatic vessels consisting of endothelium, intimal connective tissue and a poorly developed basal lamina were observed in the intestine. Scanning electron microscopy was used to compare the structure and localization of intestinal mast cells of common wolffish and rainbow trout

  18. Subclinical hypothyroidism after vascular complicated pregnancy

    NARCIS (Netherlands)

    Zanden, M. van der; Hop-de Groot, R.J.; Sweep, F.C.; Ross, H.A.; Heijer, M. den; Spaanderman, M.E.A.

    2013-01-01

    OBJECTIVE: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions. METH

  19. Vascularity in the reptilian spectacle.

    Science.gov (United States)

    Mead, A W

    1976-07-01

    Vascularization of the spectacle or brille of the reptile was demonstrated by biomicroscopy, histology, fluorescein (in vivo), and Microfil silicone rubber (in situ) injections. This unusual vascularity provides new evidence for reassessment of the origin and development of this structure, and a useful tool with which to do so.

  20. Nature's rheologists: Lymphatic endothelial cells control migration in response to shear stress

    Science.gov (United States)

    Fuller, Gerald; Dunn, Alex; Surya, Vinay

    2015-03-01

    Endothelial cells (ECs) line the inner surface of blood and lymphatic vessels and are sensitive to fluid flow as part of their physiological function. EC organization, migration and vessel development are profoundly influenced by shear stresses, with important implications in cardiovascular disease and tumor metastasis. How ECs sense fluid flow is a central and unanswered question in cardiovascular biology. We developed a high-throughput live-cell flow chamber that models the gradients in wall shear stress experienced by ECs in vivo. Live-cell imaging allows us to probe cellular responses to flow, most notably EC migration, which has a key role in vessel remodeling. We find that most EC subtypes, including ECs from the venous, arterial, and microvascular systems, migrate in the flow direction. In contrast, human lymphatic microvascular ECs (hLMVECs) migrate against flow and up spatial gradients in wall shear stress. Further experiments reveal that hLMVECs are sensitive to the magnitude, direction, and the local spatial gradients in wall shear stress. Lastly, recent efforts have aimed to link this directional migration to spatial gradients in cell-mediated small molecule emission that may be linked to the gradient in wall shear stress.

  1. Imported lymphatic filariasis in an Indian immigrant to iran.

    Directory of Open Access Journals (Sweden)

    Eshrat Beigom Kia

    2014-03-01

    Full Text Available Lymphatic filariasis (LF, a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical characteristics of microfilaria and PCR sequencing.

  2. [Long-term development of Permacath Quinton catheters used as a vascular access route for extra-renal detoxification].

    Science.gov (United States)

    Dupont, D; Morinière, P; Pourchez, T; el Esper, N; Fournier, A

    1994-01-01

    Between July 1984 and July 1991, we have inserted surgically 147 Permcath Quinton catheters in 126 uremic patients for the following reasons: group I: necessity of hemodialysis without vascular access for acute (group Ia: 44 patients) or chronic renal failure (group Ib: 11 patients); group II: difficulty of creation or loss of vascular access (group II: 45 patients); group III: hemodialysis for patients with short life expectation or contraindications for vascular access on their limbs (group III: 26 patients). The duration of use (+/- SD and range) were respectively for each group: 1.6 +/- 2 (0-10); 3.4 +/- 2.8 (1-11); 7.4 +/- 11 (0-50); 6.7 +/- 8.7 (0.1-34.5) months. Seventeen patients (group IV) coming from groups Ib and II preferred to go on with the use of their catheter for 10.5 +/- 13.5 (0.1-50) months rather than to use their arteriovenous fistula. The complications observed on whole population were: 11 septicemia responsible of 2 deaths, 9 cutaneous local infections, 28 total obstructions of the catheter, 17 partial obstructions with insufficient flow; 10 destructions of the catheter. In conclusion the Permcath Quinton catheter is an adequate long term vascular access for hemodialysis. It is well tolerated since it is preferred to the usual arteriovenous fistula by many patients who have both. The incidence of infection is low. However, obstruction (partial ou total) is frequent (29%), necessitating local fibrinolytic treatment.

  3. Effect of hepatoma H22 on lymphatic endothelium in vitro

    Institute of Scientific and Technical Information of China (English)

    Hua Yu; Hong-Zhi Zhou; Chun-Mei Wang; Xiao-Ming Gu; Bo-Rong Pan

    2004-01-01

    AIM: To determine the effect of metastatic hepatoma cells on lymphangioma-derived endothelium, and to establish in vitro model systems for assessing metastasis-related response of lymphatic endothelium.METHODS: Benign lymphangioma, induced by intraperitonea linjection of the incomplete Freund's adjuvant in BALB/c mice, was embedded in fibrin gel or digested and then cultured in the conditioned medium derived from hepatoma H22. Light and electron microscopy, and the transwell migration assay were used to determine the effect of H22 on tissue or cell culture. Expressions of Flt-4, c-Fos, proliferating cell nuclear antigen (PCNA), and inducible nitric oxide synthase (iNOS) in cultured cells, and content of nitric oxide in culture medium were also examined.RESULTS: The embedded lymphangioma pieces gave rise to array of capillaries, while separated cells from lymphangioma grew to a cobblestone-like monolayer. H22 activated growth and migration of the capillaries and cells, induced expressions of Flt-4, c-Fos, PCNA and iNOS in cultured cells, and significantly increased the content of NO in the culture medium.CONCLUSION: Lymphangioma-derived cells keep the differentiated phenotypes of lymphatic endothelium, and the models established in this study are feasible for in vitro study of metastasis-related response of lymphatic endothelium.

  4. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  5. Scarpa Fascia Preservation in Abdominoplasty: Does It Preserve the Lymphatics?

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2015-08-01

    The course of the cutaneous lymphatic collectors of the abdominal wall in relation to the Scarpa fascia is unclear in the literature. Preserving the Scarpa fascia in the lower abdomen to reduce the seroma rate following abdominoplasty has been suggested based on the assumption that the lower abdominal lymphatics run deep to this layer along their entire course. Using the previously described technique, the superficial lymphatic drainage of eight hemiabdomen specimens from four fresh human cadavers was investigated. The upper and lower abdominal collectors originated at the umbilical and midline watershed areas in a subdermal plane by the union of precollectors draining the dermis. In the lower abdomen, the depth of the collectors gradually increased in the subcutaneous fat as they coursed toward the groin. They eventually pierced the Scarpa fascia before draining into the superficial inguinal nodes located deep to this layer. The transition from the supra- to the infra-Scarpa fascia plane occurred within 2 to 3 cm of the inguinal ligament in 95 percent of the collectors. In the four cadavers studied, preserving the Scarpa fascia during abdominoplasty would not preserve the lower abdominal collectors.

  6. A critical role for lymphatic endothelial heparan sulfate in lymph node metastasis

    Directory of Open Access Journals (Sweden)

    Srinivasan R Sathish

    2010-12-01

    Full Text Available Abstract Background Lymph node metastasis constitutes a key event in tumor progression. The molecular control of this process is poorly understood. Heparan sulfate is a linear polysaccharide consisting of unique sulfate-modified disaccharide repeats that allow the glycan to bind a variety of proteins, including chemokines. While some chemokines may drive lymphatic trafficking of tumor cells, the functional and genetic importance of heparan sulfate as a possible mediator of chemokine actions in lymphatic metastasis has not been reported. Results We applied a loss-of-function genetic approach employing lymphatic endothelial conditional mutations in heparan sulfate biosynthesis to study the effects on tumor-lymphatic trafficking and lymph node metastasis. Lymphatic endothelial deficiency in N-deacetylase/N-sulfotransferase-1 (Ndst1, a key enzyme involved in sulfating nascent heparan sulfate chains, resulted in altered lymph node metastasis in tumor-bearing gene targeted mice. This occurred in mice harboring either a pan-endothelial Ndst1 mutation or an inducible lymphatic-endothelial specific mutation in Ndst1. In addition to a marked reduction in tumor metastases to the regional lymph nodes in mutant mice, specific immuno-localization of CCL21, a heparin-binding chemokine known to regulate leukocyte and possibly tumor-cell traffic, showed a marked reduction in its ability to associate with tumor cells in mutant lymph nodes. In vitro modified chemotaxis studies targeting heparan sulfate biosynthesis in lymphatic endothelial cells revealed that heparan sulfate secreted by lymphatic endothelium is required for CCL21-dependent directional migration of murine as well as human lung carcinoma cells toward the targeted lymphatic endothelium. Lymphatic heparan sulfate was also required for binding of CCL21 to its receptor CCR7 on tumor cells as well as the activation of migration signaling pathways in tumor cells exposed to lymphatic conditioned medium

  7. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

    Directory of Open Access Journals (Sweden)

    Ali Khan A

    2013-07-01

    Full Text Available Arshad Ali Khan, Jahanzeb Mudassir, Noratiqah Mohtar, Yusrida Darwis School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia Abstract: The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects

  8. Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo.

    Science.gov (United States)

    Cox, Christopher M; D'Agostino, Susan L; Miller, Melanie K; Heimark, Ronald L; Krieg, Paul A

    2006-08-01

    The peptide growth factor apelin is the high affinity ligand for the G-protein-coupled receptor APJ. During embryonic development of mouse and frog, APJ receptor is expressed at high levels in endothelial precursor cells and in nascent vascular structures. Characterization of Xenopus apelin shows that the sequence of the bioactive region of the peptide is perfectly conserved between frogs and mammals. Embryonic expression studies indicate that apelin is expressed in, or immediately adjacent to, a subset of the developing vascular structures, particularly the intersegmental vessels. Experimental inhibition of either apelin or APJ expression, using antisense morpholino oligos, results in elimination or disruption of intersegmental vessels in a majority of embryos. In gain of function experiments, apelin peptide is a potent angiogenic factor when tested using two in vivo angiogenesis assays, the frog embryo and the chicken chorioallantoic membrane. Furthermore, studies using the mouse brain microvascular cell line bEnd.3 show that apelin acts as a mitogenic, chemotactic and anti-apoptotic agent for endothelial cells in culture. Finally, we show that, similar to a number of other angiogenic factors, expression of the apelin gene is increased under conditions of hypoxia. Taken together, these studies indicate that apelin is required for normal vascular development in the frog embryo and has properties consistent with a role during normal and pathological angiogenesis.

  9. Clear-cut observation of clearance of sustainable upconverting nanoparticles from lymphatic system of small living mice

    Science.gov (United States)

    Park, Hye Sun; Nam, Sang Hwan; Kim, Jongwoo; Shin, Hyung Seon; Suh, Yung Doug; Hong, Kwan Soo

    2016-06-01

    The significance of lymphatic system has gathered great attention for immunotechnology related to cancer metastasis and immunotherapy. To develop innovative immunodiagnostics and immunotherapy in in vivo environments, it is very important to understand excretion pathways and clearance of injected cargoes. Herein, we employed Tm3+-doped upconverting nanoparticles (UCNPs) with versatile advantages suitable for long-term non-invasive in vivo optical imaging and tracking. Transport and retention of the UCNPs in the lymphatic system were evaluated with high-quality NIR-to-NIR upconversion luminescence (UCL) imaging. We obtained their kinetic luminescence profiles for the injection site and sentinel lymph node (SLN) and observed luminescence signals for one month; we also examined UCL images in SLN tissues, organs, and faeces at each time point. We speculate that the injected UCNPs in a footpad of a small mouse are transported rapidly from the lymphatic system to the blood system and then eventually result in an efficient excretion by the hepatobiliary route. These results will support development of novel techniques for SLN biopsy as well as immunotechnology.

  10. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

    Directory of Open Access Journals (Sweden)

    Katarzyna Koltowska

    2015-12-01

    Full Text Available Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.

  11. A brief perspective on the diverging theories of lymphatic targeting with colloids.

    Science.gov (United States)

    Siram, Karthik; Marslin, Gregory; Raghavan, Chellan Vijaya; Balakumar, Krishnamoorthy; Rahman, Habibur; Franklin, Gregory

    2016-01-01

    For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids.

  12. [Advances in the research of the peritoneal lymphatic stomata in human].

    Science.gov (United States)

    Li, H; Li, J

    2000-12-01

    Peritoneal lymphatic stomata are small openings of the subperitoneal lymphatic vessels on the free surface of the mesothelium. The peritoneal cavity is connected with lymphatic system via these small openings which are considered to be the main passage-way that can absorb matter from the peritoneal cavity. The lymphatic stomata are claimed to be involved in many clinic procedures, such as ascites elimination; ultrafiltration failure on the continuous ambulatory peritoneal dialysis; metastasis of tumor cells from the peritoneal cavity, and so on. It was reported that the cellular factor-NO(i.e. endothelium-derived relaxing factor, EDRF) can enhance the patency of the stomata and lymphatic absorption of the stomata by stimulating guanylate way, then increasing the concentration of the cGMP, decreasing the concentration of the [Ca2+] and as a result diastole the lymphatic stomata. Some traditional Chinese medicines, which can enhance absorption of ascites, have a regulative function on the stomata by enhancing the NO concentration.

  13. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

    DEFF Research Database (Denmark)

    Koltowska, Katarzyna; Lagendijk, Anne Karine; Pichol-Thievend, Cathy;

    2015-01-01

    during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter...... cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.......Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics...

  14. Comparison of vascularized supraclavicular lymph node transfer and lymphaticovenular anastomosis for advanced stage lower extremity lymphedema.

    Science.gov (United States)

    Akita, Shinsuke; Mitsukawa, Nobuyuki; Kuriyama, Motone; Kubota, Yoshitaka; Hasegawa, Masakazu; Tokumoto, Hideki; Ishigaki, Tatsuya; Togawa, Takashi; Kuyama, Junpei; Satoh, Kaneshige

    2015-05-01

    Vascularized lymph node transfer has become a popular surgical option to improve lower extremity lymphedema (LEL), although potential donor sites are limited. The free supraclavicular flap with deep cervical lymph nodes has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection. However, the effectiveness of this procedure has not yet been evaluated. Vascularized supraclavicular lymph node transfer (VSLNT) was performed for patients with International Society of Lymphology late stage II or more severe LEL. The results were compared with lymphaticovenular anastomosis (LVA) performed for patients with the same stages of severity. To evaluate improvement in lymphatic function, indocyanine green lymphography and lymphoscintigraphy were performed. Vascularized supraclavicular lymph node transfer was performed in 13 limbs of 13 patients. The results were compared with 43 limbs of 33 patients who underwent multiple LVA. No severe complications were observed in either group. Improvement in lymphatic function, as measured by the LEL index, was 26.5 ± 4.4 and 21.2 ± 2.0 in the VSLNT and LVA groups, respectively. Lymphatic function was improved in 7 cases in the VSLNT group and 10 cases in the LVA group. Vascularized supraclavicular lymph node transfer is an effective technique for the treatment of advanced stage LEL. Lymphaticovenular anastomosis is also effective, but to a lesser degree than VSLNT. However, LVA is less invasive and requires a shorter hospital stay.

  15. Antifilarial activity of gum from Moringa oleifera Lam. on human lymphatic filaria Brugia malayi

    Directory of Open Access Journals (Sweden)

    V Kushwaha

    2011-01-01

    Full Text Available Aim: Currently available antifilarial drugs diethylcarbamazine, ivermectin and albendazole and their combinations, are not able to control lymphatic filariasis. Therefore, a better antifilarial agent is urgently required for proper management of the disease. Materials and Methods: In this study, we evaluated the antifilarial activity of gum extract of plant Moringa oleifera Lam. against the human lymphatic filarial parasite Brugia malayi using adult worms and microfilariae (mf in two in vitro assays (motility and inhition in MTT reduction for viability and two animal models, primary (Meriones unguiculatus implanted with B. malayi adult worms in the peritoneal cavity and secondary (subcutaneous B. malayi infective larvae induced Mastomys coucha, the model closer to the natural human filarial infection screens. Results: The gum extract inhibited 100% motility (irreversible loss of motility of mf and inhibited more than 56% MTT reduction potential of the adult female worms. The extract was safe in cytotoxicity test using Vero cell line, therefore followed in vivo in primary and secondary screens. In primary screen, the extract (5×500 mg/kg caused 69% macrofilaricidal and 83% sterilization of female worms and 44% macrofilaricidal activity in secondary screen (5 × 1000 mg/kg by oral route. Conclusion: Thus, it is concluded that the gum of the plant is macrofilaricidal in both in vitro and in vivo and may provide valuable leads for design and development of new antifilarial agents. This is the first ever report on the antifilarial efficacy of M. oleifera.

  16. Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

    Directory of Open Access Journals (Sweden)

    R Anuradha

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

  17. Immunoprophylactic potential of filarial glutathione-s-transferase in lymphatic filariaisis

    Institute of Scientific and Technical Information of China (English)

    BalM; MandalN; AcharyKG; DasMK; KarSK

    2011-01-01

    Objective:To elucidates the immunoprophylactic potential of glutathion-s-transferase (GST) from cattle filarial parasite Setaria digitata (S. digitata) against lymphatic filariasis. Methods:GST was purified through affinity chromatography (SdGST) and chacterized by SDS-PAGE and Nano-LC MS/MS analysis. Antibody isotypes to SdGST were measured by ELISA. Antibody dependant cellular cytotoxicity (ADCC) was performed in vitro using sera from immunized animals and immune individuals. T-cell proliferation and cytokine response to SdGST in different groups of filariasis were measured. Immunoprophylactic potential of SdGST was evaluate in animal model. Results: SdGST exhibited 30-fold enhancement of enzyme activity over crude parasitic extract. It was found to be 26 kDa by SDS-PAGE. Nano LC-MS/MS analysis followed by blast search showed 100%homology with Dirofilaria immitis (D. immitis) and only 43%with Homo sapiens (H. sapiens). Immunoblotting analysis showed putatively immune individuals carry significant level of antibodies to SdGST as compared with microfilaraemics. Immunized sera and sera endemic normal could neutralize the enzymatic activity of SdGST and inducing in vitro cytotoxicity of microfilariae. Peripheral blood mononuclear cells (PBMC) from endemic normals upon stimulation with SdGST showed a mixed type of Th1/Th2 response. SdGST immunization clear microfilariae from circulation in S. digitata implanted mastomys. Conclusions:The heterologous GST could be potentially developed as a vaccine candidate against lymphatic filarial parasite.

  18. OCTOPUS-LIKE 2, a novel player in Arabidopsis root and vascular development, reveals a key role for OCTOPUS family genes in root metaphloem sieve tube differentiation.

    Science.gov (United States)

    Ruiz Sola, M Aguila; Coiro, Mario; Crivelli, Simona; Zeeman, Samuel C; Schmidt Kjølner Hansen, Signe; Truernit, Elisabeth

    2017-09-06

    Protophloem and metaphloem sieve tubes are essential for transporting carbohydrates and signalling molecules towards sink tissues. OCTOPUS (OPS) was previously identified as an important regulator of protophloem differentiation in Arabidopsis roots. Here, we investigated the role of OCTOPUS-LIKE 2 (OPL2), a gene homologous to OPS. OPL2 expression patterns were analysed, and functional equivalence of OPS and OPL2 was tested. Mutant and double mutant phenotypes were investigated. OPS and OPL2 displayed overlapping expression patterns and a high degree of functional overlap. A mutation in OPL2 revealed redundant functions of OPS and OPL2 in developmental processes in which OPS was known to play a role, notably cotyledon vascular patterning and protophloem development. Moreover, we also uncovered redundant roles for OPS and OPL2 in leaf vascular patterning and, most interestingly, metaphloem sieve tube differentiation. Our results reveal a novel OPS-like protein that, together with OPS, is an important regulator of vascular patterning, root growth and phloem development. OPS and OPL2 are the first genes identified that play a role in metaphloem sieve tube differentiation. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  19. Method for the quantitative measurement of collecting lymphatic vessel contraction in mice

    Directory of Open Access Journals (Sweden)

    Shan Liao

    2014-07-01

    Full Text Available Collecting lymphatic vessels are critical for the transport of lymph and its cellular contents to lymph nodes for both immune surveillance and the maintenance of tissue-fluid balance. Collecting lymphatic vessels drive lymph flow by autonomous contraction of smooth muscle cells that cover these vessels. Here we describe methods using intravital microscopy to image and quantify collecting lymphatic vessel contraction in mice. Our methods allow for the measurement of the strength of lymphatic contraction of an individual lymphangion in a mouse, which has not yet been demonstrated using other published methods. The ability to study murine collecting lymphatic vessel contraction—using the methods described here or other recently published techniques—allows the field to dissect the molecular mechanisms controlling lymphatic pumping under normal and pathological conditions using the wide variety of molecular tools and genetic models available in the mouse. We have used our methods to study lymphatic contraction in physiological and inflammatory conditions. The methods described here will facilitate the further study of lymphatic function in other pathological conditions that feature lymphatic complications.

  20. Endogenous TNFα orchestrates the trafficking of neutrophils into and within lymphatic vessels during acute inflammation

    Science.gov (United States)

    Arokiasamy, Samantha; Zakian, Christian; Dilliway, Jessica; Wang, Wen; Nourshargh, Sussan; Voisin, Mathieu-Benoit

    2017-01-01

    Neutrophils are recognised to play a pivotal role at the interface between innate and acquired immunities following their recruitment to inflamed tissues and lymphoid organs. While neutrophil trafficking through blood vessels has been extensively studied, the molecular mechanisms regulating their migration into the lymphatic system are still poorly understood. Here, we have analysed neutrophil-lymphatic vessel interactions in real time and in vivo using intravital confocal microscopy applied to inflamed cremaster muscles. We show that antigen sensitisation of the tissues induces a rapid but transient entry of tissue-infiltrated neutrophils into lymphatic vessels and subsequent crawling along the luminal side of the lymphatic endothelium. Interestingly, using mice deficient in both TNF receptors p55 and p75, chimeric animals and anti-TNFα antibody blockade we demonstrate that tissue-release of TNFα governs both neutrophil migration through the lymphatic endothelium and luminal crawling. Mechanistically, we show that TNFα primes directly the neutrophils to enter the lymphatic vessels in a strictly CCR7-dependent manner; and induces ICAM-1 up-regulation on lymphatic vessels, allowing neutrophils to crawl along the lumen of the lymphatic endothelium in an ICAM-1/MAC-1-dependent manner. Collectively, our findings demonstrate a new role for TNFα as a key regulator of neutrophil trafficking into and within lymphatic system in vivo. PMID:28287124

  1. A New Technique to Map the Lymphatic Distribution and Alignment of the Penis.

    Science.gov (United States)

    Long, Liu Yan; Qiang, Pan Fu; Ling, Tao; Wei, Zhang Yan; Long, Zhang Yu; Shan, Meng; Rong, Li Shi; Li, Li Hong

    2015-08-01

    The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two-dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three-dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1-2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface

  2. The Lymphatic Anatomy of the Lower Eyelid and Conjunctiva and Correlation with Postoperative Chemosis and Edema.

    Science.gov (United States)

    Shoukath, Sajna; Taylor, G Ian; Mendelson, Bryan C; Corlett, Russell J; Shayan, Ramin; Tourani, Saam S; Ashton, Mark W

    2017-03-01

    There are minimal data in the literature regarding the lymphatic drainage of the conjunctiva and lower eyelid and the relationship with postoperative chemosis and edema. Injection, microdissection, and histologic and radiologic studies were conducted on 12 hemifacial fresh cadaver specimens. Indocyanine green lymphography was conducted in five volunteers. Histology identified lymphatic vessels superficial and deep to the orbicularis oculi. Cadaveric dissection, injection, and radiographic studies identified interconnecting superficial and deep facial lymphatic systems and a conjunctival lymphatic network draining through the tarsal plate to the deep lymphatic system. The superficial lymphatic collectors traveled in subcutaneous fat within the lateral orbital and nasolabial fat compartments. The lateral deep lymphatic collectors traveled beneath orbicularis oculi, then through the superficial orbicularis retaining ligament, and into the sub-orbicularis oculi fat in the roof of the prezygomatic space. These vessels descended to preperiosteal fat at the level of zygomaticocutaneous ligaments to travel adjacent to the facial nerve into preauricular nodes. Indocyanine green lymphography identified correlating draining pathways laterally to the parotid nodes and medially to submandibular nodes. The authors have found that the lower eyelid and conjunctiva are drained by interconnecting superficial and deep lymphatic systems of the face. The superficial system is vulnerable to damage in incisions and dissection in the infraorbital area. The deep system is vulnerable to damage in dissection around the orbicularis retaining ligament and the zygomaticocutaneous ligaments. The authors suggest that concurrent damage to both the superficial and deep lymphatic systems, especially laterally, may be responsible for postoperative chemosis and edema.

  3. [Lymphatic system of the tongue and its role in glositis of odontogenic origin].

    Science.gov (United States)

    Chkhikvishvili, M Dzh

    2005-02-01

    In aged persons reduction of diameter of tongue lymphatic capillaries precedes thinning of the Kaarl net. In the process of tongue inflammation, lymphogenic way of inclusion in 6|6 and 8|8 teeth lower area should be stuck out with existence of alleged "Integration Centers". Lymphatic knots and lymphatic ducts are in prevailed placed in corresponding tissues of lower-chin and lower teeth. Lymphatic-muscular system and its anatomical links and age-related changeability raise the special interest during odontogenic infections with tongue inflammation.

  4. Fluorescence microlymphography: diagnostic potential in lymphedema and basis for the measurement of lymphatic pressure and flow velocity.

    Science.gov (United States)

    Bollinger, A; Amann-Vesti, B R

    2007-06-01

    Fluorescence microlymphography (FML) is an almost atraumatic technique used to visualize the superficial skin network of initial lymphatics through the intact skin of man. Visualization was performed with an incident light fluorescence microscope following subepidermal injection of minute amounts of FITC-dextran 150,000 using microneedles. Emanating from the bright dye depot, the surrounding network of microvessels is filled, documentation performed by photography or video film. In congenital Milroy lymphedema, a lack of microlymphatics (aplasia) is typical while in other primary lymphedemas and in secondary lymphedema after mastectomy or irradiation of proximal lymph nodes, the network remains intact but the depicted area is enlarged. Lymphatic microangiopathy characterized by obliterations of capillary meshes or mesh segments develops in phleboedema with trophic skin changes, progressive systemic sclerosis and Fabry's disease. In lipedema, lymphatic microaneurysms are stained. Microlymphatic pressure may also be measured using FML. For this purpose, glass micropipettes are inserted into the capillaries by means of a micromanipulator and pressure is determined by the servo-nulling technique. Normal subjects produced significantly lower pressure (7.9 +/- 3.4 mmHg) compared to patients with primary lymphedema (15.0 +/- 5.1 mmHg, pphysiotherapy or local application of prostaglandins. Additionally, a modification of the FML procedure can be used to measure lymphatic capillary flow velocity in controls and patients. FML is suited to confirm the clinical diagnosis of lymphedema, contributes to distinguish among various forms of edema, and is useful in clinical research. In addition, FML has also become a tool for experimental animal studies including the depiction of gastric microlymphatics, the measurement of flow velocity in the naked mouse tail, and in evaluation of lymphangiogenesis in a model of Milroy disease.

  5. Vascular injury in the United kingdom.

    Science.gov (United States)

    Stannard, Adam; Brohi, Karim; Tai, Nigel

    2011-03-01

    Surgeons working within the United Kingdom's National Health Service have an established history of clinical innovation, research, and development in the field of vascular surgery but lack a unified trauma system to deliver optimal care for patients with vascular injury. The low incidence of vascular trauma, combined with lack of regional trauma systems, works against optimal delivery of care to the polytrauma patient. Providing care, robust data capture, and opportunities for training and education in vascular injury lag behind other elective domains of vascular practice. The challenge is to define ideal care pathways, referral networks, and standards of practice and to integrate the care of such patients. In 2010, a trauma system for London was introduced; it has provided vascular surgeons with a unique opportunity to study and advance the care of patients with vascular injury. This article discusses developing trauma network issues, particularly the organization and evolution of vascular trauma services in the United Kingdom.

  6. Down-regulation of SymRK correlates with a deficiency in vascular bundle development in Phaseolus vulgaris nodules.

    Science.gov (United States)

    Sánchez-López, Rosana; Jáuregui, David; Nava, Noreide; Alvarado-Affantranger, Xóchitl; Montiel, Jesús; Santana, Olivia; Sanchez, Federico; Quinto, Carmen

    2011-12-01

    The symbiotic interaction of legumes and rhizobia results in the formation of nitrogen-fixing nodules. Nodulation depends on the finely coordinated expression of a battery of genes involved in the infection and the organogenesis processes. After Nod factor perception, symbiosis receptor kinase (SymRK) receptor triggers a signal transduction cascade essential for nodulation leading to cortical cell divisions, infection thread (IT) formation and final release of rhizobia to the intracellular space, forming the symbiosome. Herein, the participation of SymRK receptor during the nodule organogenesis in Phaseolus vulgaris is addressed. Our findings indicate that besides its expression in the nodule epidermis, in IT, and in uninfected cells of the infection zone, PvSymRK immunolocalizes in the root and nodule vascular system. On the other hand, knockdown expression of PvSymRK led to the formation of scarce and defective nodules, which presented alterations in both IT/symbiosome formation and vascular system.

  7. Intestinal Lymphatic Delivery of Praziquantel by Solid Lipid Nanoparticles: Formulation Design, In Vitro and In Vivo Studies

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    Amit Mishra

    2014-01-01

    Full Text Available The aim of the present work was to design and develop Praziquantal (PZQ loaded solid lipid nanoparticles (PZQ-SLN to improve the oral bioavailability by targeting intestinal lymphatic system. PZQ is practically insoluble in water and exhibits extensive hepatic first-pass metabolism. PZQ SLN were composed of triglycerides, lecithin and various aqueous surfactants; were optimized using hot homogenization followed by ultrasonication method. The optimized SLN had particle size of 123±3.41 nm, EE of 86.6±5.72%. The drug release of PZQ-SLN showed initial burst release followed by the sustained release. Inspite of zeta potential being around −10 mV, the optimized SLN were stable at storage conditions (5±3°C and 25±2°C/60±5% RH for six months. TEM study confirmed the almost spherical shape similar to the control formulations. Solid state characterization using differential scanning calorimeter (DSC and powder X-ray diffraction (PXRD analysis confirmed the homogeneous distribution of PZQ within the lipid matrix. The 5.81-fold increase in AUC0→∞, after intraduodenal administration of PZQ-SLN in rats treated with saline in comparison to rats treated with cycloheximide (a blocker of intestinal lymphatic pathway, confirmed its intestinal lymphatic delivery. The experimental results indicate that SLN may offer a promising strategy for improving the therapeutic efficacy and reducing the dose.

  8. VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes.

    Science.gov (United States)

    Igarashi, Yasuyuki; Chosa, Naoyuki; Sawada, Shunsuke; Kondo, Hisatomo; Yaegashi, Takashi; Ishisaki, Akira

    2016-04-01

    The direction of mesenchymal stem cell (MSC) differentiation is regulated by stimulation with various growth factors and cytokines. We recently established MSC lines, [transforming growth factor-β (TGF-β)-responsive SG‑2 cells, bone morphogenetic protein (BMP)-responsive SG‑3 cells, and TGF-β/BMP-non-responsive SG‑5 cells], derived from the bone marrow of green fluorescent protein-transgenic mice. In this study, to compare gene expression profiles in these MSC lines, we used DNA microarray analysis to characterize the specific gene expression profiles observed in the TGF-β-responsive SG‑2 cells. Among the genes that were highly expressed in the SG‑2 cells, we focused on vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), the gene product of FMS-like tyrosine kinase 4 (Flt4). We found that VEGF-C, a specific ligand of VEGFR3, significantly induced the cell proliferative activity, migratory ability (as shown by Transwell migration assay), as well as the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the SG‑2 cells. Additionally, VEGF-C significantly increased the expression of prospero homeobox 1 (Prox1) and lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1), which are lymphatic endothelial cell markers, and decreased the expression of osteogenic differentiation marker genes in these cells. By contrast, TGF-β significantly increased the expression of early-phase osteogenic differentiation marker genes in the SG‑2 cells and markedly decreased the expression of lymphatic endothelial cell markers. The findings of our study strongly suggest the following: i) that VEGF-C promotes the proliferative activity and migratory ability of MSCs; and ii) VEGF-C and TGF-β reciprocally regulate MSC commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes, respectively. Our findings provide new insight into the molecular mechanisms underlying the regenerative ability of MSCs.

  9. Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.

    Science.gov (United States)

    Rebourcet, Diane; Wu, Junxi; Cruickshanks, Lyndsey; Smith, Sarah E; Milne, Laura; Fernando, Anuruddika; Wallace, Robert J; Gray, Calum D; Hadoke, Patrick W F; Mitchell, Rod T; O'Shaughnessy, Peter J; Smith, Lee B

    2016-06-01

    The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.

  10. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair.

    Science.gov (United States)

    Xu, Qiang; Wang, Yanshu; Dabdoub, Alain; Smallwood, Philip M; Williams, John; Woods, Chad; Kelley, Matthew W; Jiang, Li; Tasman, William; Zhang, Kang; Nathans, Jeremy

    2004-03-19

    Incomplete retinal vascularization occurs in both Norrie disease and familial exudative vitreoretinopathy (FEVR). Norrin, the protein product of the Norrie disease gene, is a secreted protein of unknown biochemical function. One form of FEVR is caused by defects in Frizzled-4 (Fz4), a presumptive Wnt receptor. We show here that Norrin and Fz4 function as a ligand-receptor pair based on (1) the similarity in vascular phenotypes caused by Norrin and Fz4 mutations in humans and mice, (2) the specificity and high affinity of Norrin-Fz4 binding, (3) the high efficiency with which Norrin induces Fz4- and Lrp-dependent activation of the classical Wnt pathway, and (4) the signaling defects displayed by disease-associated variants of Norrin and Fz4. These data define a Norrin-Fz4 signaling system that plays a central role in vascular development in the eye and ear, and they indicate that ligands unrelated to Wnts can act through Fz receptors.

  11. XYLEM INTERMIXED WITH PHLOEM1, a leucine-rich repeat receptor-like kinase required for stem growth and vascular development in Arabidopsis thaliana.

    Science.gov (United States)

    Bryan, Anthony C; Obaidi, Adam; Wierzba, Michael; Tax, Frans E

    2012-01-01

    The regulation of cell specification in plants is particularly important in vascular development. The vascular system is comprised two differentiated tissue types, the xylem and phloem, which form conductive elements for the transport of water, nutrients and signaling molecules. A meristematic layer, the procambium, is located between these two differentiated cell types and divides to initiate vascular growth. We report the identification of a receptor-like kinase (RLK) that is expressed in the vasculature. Histochemical analyses of mutants in this kinase display an aberrant accumulation of highly lignified cells, typical of xylem or fiber cells, within the phloem. In addition, phloem cells are sometimes located adjacent to xylem cells in these mutants. We, therefore, named this RLK XYLEM INTERMIXED WITH PHLOEM 1 (XIP1). Analyses of longitudinal profiles of xip1 mutant stems show malformed cell files, indicating defects in oriented cell divisions or cell morphology. We propose that XIP1 prevents ectopic lignification in phloem cells and is necessary to maintain the organization of cell files or cell morphology in conductive elements.

  12. Lymphatic metastasis and nm23H1 genetic instability in Chinese colon cancer patients

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Su; Ji-Cheng Li

    2004-01-01

    function,and shows an important clinical significance in predicting lymphatic metastasis of colon cancer. MSI and LOH may separately control the development of sporadic colon cancer with different pathways. LOH mostly arises in the late period of sporadic colon cancer and endows a high aggressive and poor prognostic phenotype. By compassion, MSI may be an early period molecule marker for sporadic colon cancer,enhanced expression of nm23H1 protein can effectively inhibit colon cancer metastasis and improve prognosis of sporadic colon cancer patients.

  13. Spatio-temporal changes of lymphatic contractility and drainage patterns following lymphadenectomy in mice.

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    Sunkuk Kwon

    Full Text Available OBJECTIVE: To investigate the redirection of lymphatic drainage post-lymphadenectomy using non-invasive near-infrared fluorescence (NIRF imaging, and to subsequently assess impact on metastasis. BACKGROUND: Cancer-acquired lymphedema arises from dysfunctional fluid transport after lymphadenectomy performed for staging and to disrupt drainage pathways for regional control of disease. However, little is known about the normal regenerative processes of the lymphatics in response to lymphadenectomy and how these responses can be accelerated, delayed, or can impact metastasis. METHODS: Changes in lymphatic "pumping" function and drainage patterns were non-invasively and longitudinally imaged using NIRF lymphatic imaging after popliteal lymphadenectomy in mice. In a cohort of mice, B16F10 melanoma was inoculated on the dorsal aspect of the paw 27 days after lymphadenectomy to assess how drainage patterns affect metastasis. RESULTS: NIRF imaging demonstrates that, although lymphatic function and drainage patterns change significantly in early response to popliteal lymph node (PLN removal in mice, these changes are transient and regress dramatically due to a high regenerative capacity of the lymphatics and co-opting of collateral lymphatic pathways around the site of obstruction. Metastases followed the pattern of collateral pathways and could be detected proximal to the site of lymphadenectomy. CONCLUSIONS: Both lymphatic vessel regeneration and co-opting of contralateral vessels occur following lymphadenectomy, with contractile function restored within 13 days, providing a basis for preclinical and clinical investigations to hasten lymphatic repair and restore contractile lymphatic function after surgery to prevent cancer-acquired lymphedema. Patterns of cancer metastasis after lymphadenectomy were altered, consistent with patterns of re-directed lymphatic drainage.

  14. Predictive factors for lymph node metastasis in early gastric cancer with lymphatic invasion after endoscopic resection.

    Science.gov (United States)

    Park, Ji Won; Ahn, Sangjeong; Lee, Hyuk; Min, Byung-Hoon; Lee, Jun Haeng; Rhee, Poong-Lyul; Kim, Kyoung-Mee; Kim, Jae J

    2017-04-04

    Lymph node (LN) metastasis is found in only about 5-10% of the patients who undergo additional surgery after non-curative endoscopic resection. Lymphatic invasion after endoscopic submucosal dissection (ESD) is regarded as non-curative resection due to risk of reginal LN metastasis. This study was aimed to identify clinicopathologic predictive factors for LN metastasis in early gastric cancer (EGC) with lymphatic invasion after endoscopic resection. Among a total of 2036 patients who underwent endoscopic resection for EGC at Samsung Medical Center from April 2000 to May 2011, 146 patients were diagnosed with lymphatic invasion. And 123 patients who had gastrectomy with LN dissection due to presence of lymphatic invasion as one of the non-curative factors were included in this study. Demographics, endoscopic tumor findings, histological findings, surgical findings with pathologic reports, and follow-up data were collected from the patient's medical records. Pathological re-evaluation of resected specimens was performed. Among a total of 123 patients, LN metastases were found in seven patients (5.7%). The univariate analysis revealed that the LN metastasis was significantly more frequent in patients with certain morphology of lymphatic invasion that shows adhesion to endothelium of lymphatic tumor emboli (p = 0.016), higher number of lymphatic tumor emboli in whole section (p < 0.001) and papillary adenocarcinoma component (p = 0.024). In multivariate analysis, the number of lymphatic tumor emboli [OR 93.5, 95% CI (2.62-3330.81)] and the presence of papillary adenocarcinoma component [OR 552.5, 95% CI (1.20-254871.81)] were identified as independent predictors of LN metastasis in patients with lymphatic invasion after endoscopic resection. The number of lymphatic tumor emboli and the presence of papillary adenocarcinoma component were significant predictors for LN metastasis in patients with lymphatic invasion after endoscopic resection.

  15. Hypercholesterolaemia and vascular dementia.

    Science.gov (United States)

    Appleton, Jason P; Scutt, Polly; Sprigg, Nikola; Bath, Philip M

    2017-07-15

    Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors-diabetes, hypercholesterolaemia, hypertension and smoking-are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here. © 2017 The Author(s).

  16. Manual lymphatic drainage for lymphedema following breast cancer treatment

    Science.gov (United States)

    Ezzo, Jeanette; Manheimer, Eric; McNeely, Margaret L; Howell, Doris M; Weiss, Robert; Johansson, Karin I; Bao, Ting; Bily, Linda; Tuppo, Catherine M; Williams, Anne F; Karadibak, Didem

    2016-01-01

    Background More than one in five patients who undergo treatment for breast cancer will develop breast cancer-related lymphedema (BCRL). BCRL can occur as a result of breast cancer surgery and/or radiation therapy. BCRL can negatively impact comfort, function, and quality of life (QoL). Manual lymphatic drainage (MLD), a type of hands-on therapy, is frequently used for BCRL and often as part of complex decongestive therapy (CDT). CDT is a fourfold conservative treatment which includes MLD, compression therapy (consisting of compression bandages, compression sleeves, or other types of compression garments), skin care, and lymph-reducing exercises (LREs). Phase 1 of CDT is to reduce swelling; Phase 2 is to maintain the reduced swelling. Objectives To assess the efficacy and safety of MLD in treating BCRL. Search methods We searched Medline, EMBASE, CENTRAL, WHO ICTRP (World Health Organization’s International Clinical Trial Registry Platform), and Cochrane Breast Cancer Group’s Specialised Register from root to 24 May 2013. No language restrictions were applied. Selection criteria We included randomized controlled trials (RCTs) or quasi-RCTs of women with BCRL. The intervention was MLD. The primary outcomes were (1) volumetric changes, (2) adverse events. Secondary outcomes were (1) function, (2) subjective sensations, (3) QoL, (4) cost of care. Data collection and analysis We collected data on three volumetric outcomes. (1) LE (lymphedema) volume was defined as the amount of excess fluid left in the arm after treatment, calculated as volume in mL of affected arm post-treatment minus unaffected arm post-treatment. (2) Volume reduction was defined as the amount of fluid reduction in mL from before to after treatment calculated as the pretreatment LE volume of the affected arm minus the post-treatment LE volume of the affected arm. (3) Per cent reduction was defined as the proportion of fluid reduced relative to the baseline excess volume, calculated as volume

  17. Lymphatic filariasis in Brazil: epidemiological situation and outlook for elimination

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    Fontes Gilberto

    2012-11-01

    Full Text Available Abstract Since the World Health Assembly’s (Resolution WHA 50.29, 1997 call for the elimination of lymphatic filariasis by the year 2020, most of the endemic countries identified have established programmes to meet this objective. In 1997, a National Lymphatic Filariasis Elimination Plan was drawn up by the Ministry of Health of Brazil, creating local programs for the elimination of Bancroftian filariasis in areas with active transmission. Based on a comprehensive bibliographic search for available studies and reports of filariasis epidemiology in Brazil, current status of this parasitic infection and the outlook for its elimination in the country were analysed. From 1951 to 1958 a nationwide epidemiological study conducted in Brazil confirmed autochthonous transmission of Bancroftian filariasis in 11 cities of the country. Control measures led to a decline in parasite rates, and in the 1980s only the cities of Belém in the Amazonian region (Northern region and Recife (Northeastern region were considered to be endemic. In the 1990s, foci of active transmission of LF were also described in the cities of Maceió, Olinda, Jaboatão dos Guararapes, and Paulista, all in the Northeastern coast of Brazil. Data provide evidence for the absence of microfilaremic subjects and infected mosquitoes in Belém, Salvador and Maceió in the past few years, attesting to the effectiveness of the measures adopted in these cities. Currently, lymphatic filariasis is a public health problem in Brazil only in four cities of the metropolitan Recife region (Northeastern coast. Efforts are being concentrated in these areas, with a view to eliminating the disease in the country.

  18. Continuous taurocholic acid exposure promotes esophageal squamous cell carcinoma progression due to reduced cell loss resulting from enhanced vascular development.

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    Sho Sato

    Full Text Available BACKGROUND: Refluxogenic effects of smoking and alcohol abuse may be related to the risk of esophageal squamous cell carcinoma (ESCC. The present study attempts to clarify the effects of continuous taurocholic acid (TCA exposure, which is neither mutagenic nor genotoxic, on ESCC progression. METHODS: A squamous carcinoma cell line (ESCC-DR was established from a tumor induced in a rat model of gastroduodenal reflux. ESCC-DR cells were incubated with 2 mM TCA for ≥2 months. The effects of continuous TCA exposure were evaluated in vitro on cell morphology, growth, and invasion and in vivo on xenograft tumor growth in nude mice. Moreover, the mean level of secreted transforming growth factor (TGF-β1 and vascular endothelial growth factor (VEGF proteins in cell culture supernatants and mRNA synthesis of TGF-β1 and VEGF-A of ESCC cells were measured. The angiogenic potential was further examined by a migration assay using human umbilical vein endothelial cells (HUVECs. RESULTS: Continuous TCA exposure induced marked formation of filopodia in vitro. Expression levels of angiogenic factors were significantly higher in the cells treated with TCA than in control cells. Tumor xenografts derived from cells pre-exposed to TCA were larger and more vascularized than those derived from control cells. In addition, TCA exposure increased HUVEC migration. CONCLUSION: Continuous TCA exposure enhanced ESCC progression due to reduced cell loss in vivo. Cell loss was inhibited by TCA-induced vascular endothelial cell migration, which was mediated by TGF-β1 and VEGF-A released from ESCC cells.

  19. Effect of VEGF-C siRNA and endostatin on ring formation and proliferation of esophageal squamous cell carcinoma lymphatic endothelial cells

    Directory of Open Access Journals (Sweden)

    Zheng YP

    2016-10-01

    Full Text Available Yuping Zheng,1–3,* Miaomiao Sun,4,* Jinyan Chen,1,2 Lulu He,1,2 Na Zhao,1,2 Kuisheng Chen1,2 1Pathology Department, The First Affiliated Hospital of Zhengzhou University, 2Henan Key Laboratory of Tumor Pathology, 3Pathology Department, The Second Hospital of Shandong University, Jinan, 4Pathology Department, Henan Tumor Hospital, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Objective: To study the effects of vascular endothelial growth factor C small interfering RNA and endostatin on esophageal squamous cell carcinoma-related ring formation in vitro and proliferation of lymphatic endothelial cells.Materials and methods: KYSE150 cells were subjected to analysis of cell transfection and endostatin operation. The groups were as follows: negative group, blank group, negative plus endostatin group, endostatin group, SG1 group, SG2 group, SG1 plus endostatin group, and SG2 plus endostatin group. The esophageal cancer-related microlymphatic endothelial cells were three-dimensionally cultured. Cell Counting Kit-8 (CCK-8 assay was employed to detect cell proliferation.Results: The negative group’s three-dimensional culture result was the highest, followed by the blank group, negative plus endostatin group, endostatin group, SG2 group, SG1 group, SG1 plus endostatin group, and SG2 plus endostatin group. The quantity of living cells in the blank group was the highest, followed by the negative control, endostatin, SG2, SG1, negative plus endostatin, SG1 plus endostatin, and SG2 plus endostatin groups. Conclusion: Both vascular endothelial growth factor C small interfering RNA and endostatin could inhibit ring formation in esophageal squamous cell carcinoma and proliferation of lymphatic endothelial cells. Keywords: esophageal squamous carcinoma cells, esophageal cancer-associated lymphatic endothelial cells, VEGF-C, ring formation, proliferation

  20. Mathematical models for lymphatic filariasis transmission and control: Challenges and prospects

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    Kaliannagounder Krishnamoorthy

    2008-02-01

    Full Text Available Abstract Background Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. Discussion EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. Summary The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is

  1. A microarray analysis of two distinct lymphatic endothelial cell populations

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    Bernhard Schweighofer

    2015-06-01

    Full Text Available We have recently identified lymphatic endothelial cells (LECs to form two morphologically different populations, exhibiting significantly different surface protein expression levels of podoplanin, a major surface marker for this cell type. In vitro shockwave treatment (IVSWT of LECs resulted in enrichment of the podoplaninhigh cell population and was accompanied by markedly increased cell proliferation, as well as 2D and 3D migration. Gene expression profiles of these distinct populations were established using Affymetrix microarray analyses. Here we provide additional details about our dataset (NCBI GEO accession number GSE62510 and describe how we analyzed the data to identify differently expressed genes in these two LEC populations.

  2. Current concepts in the classification, diagnosis and treatment of vascular anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ernemann, Ulrike, E-mail: ulrike.ernemann@med.uni-tuebingen.d [Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Kramer, Ulrich; Miller, Stephan [Department of Diagnostic and Interventional Radiology, Radiological Clinic, University Hospital Tuebingen (Germany); Bisdas, Sotirios [Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Rebmann, Hans [Department of Paediatrics, Children' s Hospital, University Hospital Tuebingen (Germany); Breuninger, Helmut [Department of Dermatology, University Hospital Tuebingen (Germany); Zwick, Christine [Department of Hand, Plastic, Reconstructive and Burns Surgery, BG Trauma Clinic Tuebingen, University Hospital Tuebingen (Germany); Hoffmann, Juergen [Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen (Germany)

    2010-07-15

    Patients with extended vascular anomalies may suffer from significant aesthetic and functional impairment and represent a challenge to therapeutic planning, which is best met by an interdisciplinary concept. In agreement with the International Society for the Study of Vascular Anomalies (ISSVA), vascular lesions are classified into haemangiomas as proliferating endothelial tumours on the one hand and congenital vascular malformations on the other. According to the preponderant vascular channels and hemodynamic characteristics, malformations are subdivided into low flow (venous, lymphatic and capillary) lesions and high-flow malformations. Diagnostic imaging should be targeted at the specific structural and functional informations required for treatment planning. The imaging modality of choice to provide these informations is magnetic resonance imaging (MRI) supplemented by magnetic resonance angiography (MRA) with high spatial and temporal resolution. Treatment indications for haemangiomas depend on the proliferative behaviour of the lesion and comprise {beta}-blockers in order to induce involution as well as cryotherapy, laser and open surgery. Interventional radiological procedures have evolved as an essential element in an interdisciplinary treatment plan for vascular malformations and include percutaneous sclerotherapy with ethanol and OK-432 for venous and lymphatic malformations and transarterial embolization for high-flow lesions.

  3. Successful treatment of plastic bronchitis by selective lymphatic embolization in a Fontan patient.

    Science.gov (United States)

    Dori, Yoav; Keller, Marc S; Rychik, Jack; Itkin, Maxim

    2014-08-01

    Plastic bronchitis is a rare and often fatal complication of single-ventricle surgical palliation after total cavopulmonary connection. Although lymphatic abnormalities have been postulated to play a role in the disease process, the etiology and pathophysiology of this complication remain incompletely understood. Here we report on the etiology of plastic bronchitis in a child with total cavopulmonary connection as demonstrated by magnetic resonance (MR) lymphangiography. We also report on a new treatment of this disease. The patient underwent noncontrast T2-weighted MR lymphatic mapping and dynamic contrast MR lymphangiography with bi-inguinal intranodal contrast injection to determine the anatomy and flow pattern of lymph in his central lymphatic system. The MRI scan demonstrated the presence of a dilated right-sided peribronchial lymphatic network supplied by retrograde lymphatic flow through a large collateral lymphatic vessel originating from the thoracic duct. After careful analysis of the MRI scans we performed selective lymphatic embolization of the pathologic lymphatic network and supplying vessel. This provided resolution of plastic bronchitis for this patient. Five months after the procedure, the patient remains asymptomatic off respiratory medications. Copyright © 2014 by the American Academy of Pediatrics.

  4. An Evolutionarily Conserved Role for Polydom/Svep1 during Lymphatic Vessel Formation

    NARCIS (Netherlands)

    Karpanen, Terhi; Padberg, Yvonne; Van De Pavert, Serge A.; Dierkes, Cathrin; Morooka, Nanami; Peterson-Maduro, Josi; Van De Hoek, Glenn; Adrian, Max; Mochizuki, Naoki; Sekiguchi, Kiyotoshi; Kiefer, Friedemann; Schulte, Dörte; Schulte-Merker, Stefan

    2017-01-01

    Rationale: Lymphatic vessel formation and function constitutes a physiologically and pathophysiologically important process, but its genetic control is not well understood. Objective: Here, we identify the secreted Polydom/Svep1 protein as essential for the formation of the lymphatic vasculature. We

  5. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    Science.gov (United States)

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

    DEFF Research Database (Denmark)

    Hammer, Troels; Tritsaris, Katerina; Hübschmann, Martin V;

    2009-01-01

    IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimul...

  7. EVALUATION OF MASS DRUG ADMINISTRATION FOR ELIMINATION OF LYMPHATIC FILARIASIS IN GUNTUR DISTRICT, ANDHRA PRADESH

    OpenAIRE

    Purnamma; Neelima

    2015-01-01

    BACKGROUND : Lymphatic Filariasis (LF) is a serious Socio Economic and Public Health problem in the world. In India, it is estimated that 554.2 million populations are at risk of Lymphatic Filariasis infection, in 243 implementation units (Districts). National Health Policy, 2002 aims at elimination of transmission and prevention of disability ...

  8. Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling.

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); S.J. de Vlas (Sake); J.D.F. Habbema (Dik)

    2006-01-01

    textabstractMathematical simulation models for transmission and control of lymphatic filariasis are useful tools for studying the prospects of lymphatic filariasis elimination. Two simulation models are currently being used. The first, EPIFIL, is a population-based, deterministic model that simulate

  9. Erratum: PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis

    DEFF Research Database (Denmark)

    Cao, R.H.; Bjorndahl, M.A.; Religa, P.;

    2006-01-01

    This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45.......This corrects the article "PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis", Cancer Cell, 2004, vol. 6(4), pg 333-45....

  10. A Validation Study of Near-Infrared Fluorescence Imaging of Lymphatic Vessels in Humans

    DEFF Research Database (Denmark)

    Groenlund, Jacob Hinnerup; Telinius, Niklas; Skov, Soeren Nielsen

    2017-01-01

    BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a new imaging technique that is used to visualize lymphatic vessels in humans. It has a high spatial and temporal resolution, allowing real-time visualization of lymphatic flow. METHODS AND RESULTS: The current study investigated the intra...

  11. CLOVE Syndrome (Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi): CNS Malformations and Seizures may be a Component of this Disorder

    Science.gov (United States)

    Gucev, Zoran S.; Tasic, Velibor; Jancevska, Aleksandra; Konstantinova, Marina Krstevska; Pop-Jordanova, Nada; Trajkovski, Zoran; Biesecker, Leslie G.

    2010-01-01

    A newborn girl was found to have a massive lymphatic truncal vascular malformation with overlying cutaneous venous anomaly associated with overgrown feet and splayed toes. These manifestations comprise the recently described CLOVE syndrome. She also had cranial asymmetry and developed generalized seizures, which were treated with anticonvulsants. Cranial CT showed encephalomalacia, widening of the ventricles and the sulci, hemimegalencephaly (predominantly white matter) and partial agenesis of corpus callosum. Review of the literature identified several other patients with CLOVE syndrome, some of whom were misdiagnosed as having Proteus syndrome, with strikingly similar manifestations. We conclude that CNS manifestations including hemimegalencephaly, dysgenesis of the corpus callosum, neuronal migration defects, and the consequent seizures, may be a more common manifestation of CLOVE syndrome than is presently appreciated. PMID:18816642

  12. Development of a neural network screening aid for diagnosing lower limb peripheral vascular disease from photoelectric plethysmography pulse waveforms.

    Science.gov (United States)

    Allen, J; Murray, A

    1993-02-01

    An artificial neural network (ANN) was trained to classify photoelectric plethysmographic (PPG) pulse waveforms for the diagnosis of lower limb peripheral vascular disease (PVD). PPG pulses from the lower limbs, and pre- and post-exercise Doppler ultrasound ankle to brachial systolic blood pressure ratio measurements were obtained from patients referred to a vascular investigation laboratory. A single PPG pulse from the big toe of each leg was processed and normalized, and used as input data to the ANN. The ANN outputs represented the diagnostic classifications (normal, significant PVD and major PVD) and the ANN was trained with the ankle to brachial pressure indices (ABPI). The ANN structure consisted of an input layer (50 neuron units from the PPG pulse input), a single hidden layer (15 neurons) and an output layer (3 neurons for the PVD diagnoses). The back-propagation learning algorithm was used to train the ANN for 500 epochs with a PPG training set of pulses from 100 legs. Test data for network assessment comprised pulses from a further 50 legs (20 normal and 30 PVD, of which 15 were categorized as having major disease). A network sensitivity of 93% and specificity of 85% was achieved with respect to the Doppler ABPI standard, giving a diagnostic accuracy of 90%. The results of this study indicate that a neural network can be trained to distinguish between PPG pulses from normal and diseased lower limb arteries. The simplicity of PPG measurement and neural network classification holds promise for the screening of lower limb arterial PVD.

  13. Development of novel short-term heating angioplasty: diameter and elasticity change of vascular wall ex vivo

    Science.gov (United States)

    Shimazaki, Natsumi; Kaneko, Kenji; Nakatani, Eriko; Arai, Tsunenori

    2007-02-01

    In order to investigate the optimum operation parameters on novel short-term heating (angioplasty in which we demonstrated sufficient vascular dilatation with lower pressure by heat- induced denaturation of arterial collagen. And we have also demonstrated the suppression of intimal hyperplasia in animal experiments. We need to understand the PTDB dilatation mechanism to determine the optimum operation parameters. The prototype PTDB with diameter of 3mm was used in our experiments. The internal diameters of extracted fresh porcine carotid arteries at pre- and post- PTDB dilatation were measured. Balloon parameters were follows; pressure P=2atm, peak temperature in balloon T=60-80 °C, and heating duration t=4-30s. Morphological change in the media of dilated artery with PTDB were microscopically examined with Weigert staining. Elastic properties were carried out by stress-strain measurements with calculation of young's modulus. We found that PTDB dilatation provided the effect to prevent elastic recoil. We explained that the reason of this effect might be arrangement of micro- structure in the media, i.e., heat-denatured collagen fibers sustained the elastic recoil due to rubbery elastin fibers. The arterial elasticity was not significant different after PTDB dilatation. It was suggested that there could be no compliance mismatch after PTDB dilatation in physiological range. We found that a part of PTDB dilatation mechanism, in which the vascular wall structure played an important role. The optimum operation parameters for PTDB might be determined in consideration of collagen denaturation progress and arterial composition.

  14. Development of mechanically expanded gelatin-AAc-PLLA/PLCL nanofibers for vascular tissue engineering by radiation-based techniques

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Oh; Jeong, Sung In; Seo, Da Eun; Park, Jong Seok; Gwon, Hui Jeong; Ahn, Sung Jun; Lim, Youn Mook [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Shin, Young Min [Dept. of Bioengineering, Division of Applied Chemical and Bio Engineering, Hanyang University, Seoul (Korea, Republic of)

    2015-12-15

    Vascular tissue engineering has been accessed to mimic the natural composition of the blood vessel containing inmate, media, and adventitia layers. We fabricated mechanically expanded PLLA/PLCL nanofibers using electrospinning and UTM. The pore size of the meshes was increased the gelatin immobilized AAc-PLLA/PLCL nanofibers (203.30±49.62 microns) than PLLA/PLCL nanofibers (59.99±8.66 microns) after mechanical expansion. To increase the cell adhesion and proliferation, we introduced carboxyl group, and gelatin was conjugated on them. The properties of the PLLA/PLCL nanofibers were analyzed with SEM, ATR-FTIR, TBO staining, and water contact angle measurement, general cell responses on the PLLA/PLCL nanofibers such as adhesion, proliferation, and infiltration were also investigated using smooth muscle cell (SMC). During the SMC culture, the initial viability of the cells was significantly increased on the gelatin immobilized AAc-PLLA/PLCL nanofibers, and infiltration of the cells was also enhanced on them. Therefore, gelatin immobilized AAc-PLLA/PLCL nanofibers and mechanically expanded meshes may be a good tool for vascular tissue engineering application.

  15. Adhesion in vascular biology

    OpenAIRE

    2014-01-01

    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is call...

  16. Effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats

    Institute of Scientific and Technical Information of China (English)

    Zuoli Xia; Baoling Sun; Mingfeng Yang; Dongmei Hu; Tong Zhao; Jingzhong Niu

    2006-01-01

    BACKGROUND: It has been shown that although brain does not contain lining endothelial lymphatic vessel,it has lymphatic drain.Anterior lymphatic vessel in brain tissue plays a key role in introducing brain interstitial fluid to lymphatic system;however,the significance of lymphatic drain and the affect on cerebral edema remains unclear.OBJECTIVE: To investigate the effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats.DESIGN: Randomized controlled animal study.SETTING: Institute of Cerebral Microcirulation of Taishan Medical College and Department of Neurology of Affiliated Hospital.MATERIALS:A total of 63 healthy adult male Wistar rats weighing 300-350 g were selected in this study.Forty-seven rats were used for the morphological observation induced by lymphatic drain and randomly divided into three groups:general observation group(n=12),light microscopic observation group(n=21)and electronic microscopic observation group(n=14).The rats in each group were divided into cerebral lymphatic block subgroup and sham-operation control subgroup.Sixteen rats were divided into cerebral the effect of cerebral lymphatic block on cortical evoked potential,in which the animals were randomly divided into sham-operation group(n=6)and cerebral lymphatic block group(n=10).METHODS:The experiment was carried out in the Institute of Cerebral Microcirculation of Taishan Medical College from January to August 2003.Rats in cerebral lymphatic block group were anesthetized and separated bilateral superficial and deep cervical lymph nodes under sterile condition. Superior and inferior boarders of lymph nodes were ligated the inputting and outputting channels, respectively, and then lymph node was removed so as to establish cerebral lymphatic drain disorder models. Rats in sham-operation control group were not ligated the lymphatic vessel and removed lymph nodes.and other operations were as the same as those in cerebral lymphatic block group

  17. Cardiac lymphatic dynamics after ischemia and reperfusion - experimental model

    Energy Technology Data Exchange (ETDEWEB)

    Santos, A.C. E-mail: cristina@imagem.ibili.uc.pt; Lima, J.J.P. de; Botelho, M.F.; Pacheco, M.F.; Sousa, P.; Bernardo, J.; Ferreira, N.; Goncalves, L.; Aguiar, J.; Providencia, L.A.; Pauwels, E.K.J

    1998-10-01

    The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of {sup 99m}Tc-Re{sub 2}S{sub 7} colloid ({+-}10 {mu}m), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A {gamma}-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

  18. Primary mucinous carcinoma with direct histopathologic evidence of lymphatic invasion.

    Science.gov (United States)

    Warycha, Melanie; Kamino, Hideko; Mobini, Narciss; Hale, Elizabeth K

    2006-01-01

    Primary mucinous carcinoma of the skin is a rare sweat gland neoplasm which occurs most commonly in the periorbital region. Although the tumor has a propensity for local recurrence and regional spread, distant metastases are rare. The standard treatment of primary mucinous carcinoma is wide local excision. Mohs micrographic surgery may also be utilized in cases where tissue conservation is of utmost concern. We present a case of primary mucinous carcinoma arising in the scalp, which was treated with wide local excision. A case report and literature review are presented. Histopathologic evaluation revealed a well-circumscribed neoplasm characterized by lobules and aggregates of epithelial cells embedded in abundant pools of mucin. In addition, small aggregates of neoplastic cells were found at a distance from the primary nodule, indicative of lymphatic invasion. Primary mucinous carcinoma has a high propensity for locoregional metastases and recurrence. To our knowledge, this is the first report demonstrating direct histopathologic evidence of lymphatic invasion which correlates with this tumor's biologic behavior.

  19. Self-Management Support Program for Patients With Cardiovascular Diseases: User-Centered Development of the Tailored, Web-Based Program Vascular View.

    Science.gov (United States)

    Puijk-Hekman, Saskia; van Gaal, Betsie Gi; Bredie, Sebastian Jh; Nijhuis-van der Sanden, Maria Wg; van Dulmen, Sandra

    2017-02-08

    In addition to medical intervention and counseling, patients with cardiovascular disease (CVD) need to manage their disease and its consequences by themselves in daily life. The aim of this paper is to describe the development of "Vascular View," a comprehensive, multi-component, tailored, Web-based, self-management support program for patients with CVD, and how this program will be tested in an early randomized controlled trial (RCT). The Vascular View program was systematically developed in collaboration with an expert group of 6 patients, and separately with a group of 6 health professionals (medical, nursing, and allied health care professionals), according to the following steps of the intervention mapping (IM) framework: (1) conducting a needs assessment; (2) creating matrices of change objectives; (3) selecting theory-based intervention methods and practical applications; (4) organizing methods and applications into an intervention program; (5) planning the adaption, implementation, and sustainability of the program, and (6) generating an evaluation plan. The needs assessment (Step 1) identified 9 general health problems and 8 determinants (knowledge, awareness, attitude, self-efficacy, subjective norm, intention, risk perception, and habits) of self-managing CVD. By defining performance and change objectives (Step 2), 6 topics were distinguished and incorporated into the courses included in Vascular View (Steps 3 and 4): (1) Coping With CVD and its Consequences; (2) Setting Boundaries in Daily Life; (3) Lifestyle (general and tobacco and harmful alcohol use); (4) Healthy Nutrition; (5) Being Physically Active in a Healthy Way; and (6) Interaction With Health Professionals. These courses were based on behavioral change techniques (BCTs) (eg, self-monitoring of behavior, modeling, re-evaluation of outcomes), which were incorporated in the courses through general written information: quotes from and videos of patients with CVD as role models and personalized

  20. Direct lymphangiography as treatment option of lymphatic leakage: indications, outcomes and role in patient's management.

    Science.gov (United States)

    Gruber-Rouh, Tatjana; Naguib, Nagy N N; Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin; Tsaur, Igor; Hammersting, Renate; Wichmann, Julian L; Vogl, Thomas J; Jacobi, Volkmar

    2014-12-01

    To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10)underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31),therapeutic lymphography was still successful in 58.1% of the patients. Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Alginate/chitosan microparticles for tamoxifen delivery to the lymphatic system.

    Science.gov (United States)

    Coppi, G; Iannuccelli, V

    2009-02-09

    Oral administration of the nonsteroidal anti-estrogen tamoxifen (TMX) is the treatment of choice for metastatic estrogen receptor-positive breast cancer. With the aim to improve TMX oral bioavailability and decrease its side effects, crosslinked alginate microparticles for the targeting to the lymphatic system by Peyer's patch (PP) uptake were developed and in vitro characterized. TMX was molecularly dispersed inside the microparticles and an electrostatic interaction involving the TMX tertiary amine was detected by rheological and FT-IR assays. Microparticles showed a size less than 3mum, then suitability to be taken up by M cells in PP and a positive surface charge. Moreover, TMX loading level as well as in vitro release behaviour was affected by the polymer network connected with the mannuronic/guluronic ratio of the alginate chains.

  2. [The future of vascular medicine].

    Science.gov (United States)

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step.

  3. Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1).

    Science.gov (United States)

    Schwartz, Jonathan D; Rowinsky, Eric K; Youssoufian, Hagop; Pytowski, Bronislaw; Wu, Yan

    2010-02-15

    The human vascular endothelial growth factor receptor-1 (VEGFR-1, or Flt-1) is widely expressed in normal and pathologic tissue and contributes to the pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR-1 mediated signaling is responsible for both direct tumor activation and angiogenesis. VEGFR-1 mediated activation of nonmalignant supporting cells, particularly stromal, dendritic, hematopoietic cells, and macrophages, is also likely important for cancer pathogenesis. VEGFR-1 is also hypothesized to enable the development of cancer metastases by means of activation and premetastatic localization in distant organs of bone marrow-derived hematopoietic progenitor cells, which express VEGFR-1. IMC-18F1 is a fully human IgG(1) antibody that binds to VEGFR-1 and has been associated with the inhibition of cancer growth in multiple in vitro and human tumor xenograft models. The preliminary results of phase 1 investigations have also indicated a favorable safety profile for IMC-18F1 at doses that confer antibody concentrations that are associated with relevant antitumor activity in preclinical models.

  4. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  5. Hypertensive organ damage in patients with vascular disease

    NARCIS (Netherlands)

    Vlek, A.L.M.

    2009-01-01

    Hypertension is one of the most common vascular risk factors, and is an important cause of development of different vascular diseases. The main aim of this thesis was to determine the burden of hypertension-associated vascular diseases and end-organ damage in patients with manifest vascular disease.

  6. Hypertensive organ damage in patients with vascular disease

    NARCIS (Netherlands)

    Vlek, A.L.M.

    2009-01-01

    Hypertension is one of the most common vascular risk factors, and is an important cause of development of different vascular diseases. The main aim of this thesis was to determine the burden of hypertension-associated vascular diseases and end-organ damage in patients with manifest vascular disease.

  7. Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis.

    Science.gov (United States)

    Elias, Peter M; Arbiser, Jack; Brown, Barbara E; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R

    2008-09-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

  8. Nasal lymphatics as a novel invasion and dissemination route of bacterial meningitis.

    Science.gov (United States)

    Filippidis, Aristotelis; Fountas, Kostas N

    2009-06-01

    Bacterial meningitis constitutes an infectious disease with high morbidity and mortality, characterized by complex pathophysiology. Neisseria meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b and other pathogens are capable of invading the CNS and infecting the meninges due to the incorporation of virulence factors. The pathophysiologic theories concerning the route of infection in bacterial meningitis consider a general cascade of events involving nasopharyngeal or middle ear colonization, pathogen bloodstream dissemination, blood-brain and blood-cerebrospinal fluid barriers crossing, and finally entrance of the implicated pathogen into the subarachnoid space, survival and subsequent infection. However, these theories cannot adequately explain the high percentage of negative blood cultures especially in cases of neonatal meningitis. Also, they cannot address with certainty the pathogens' entry site in to the cerebrospinal fluid, since the presence of barriers could act against bacterial infection of the meninges. In addition, experimental models of S. pneumoniae meningitis indicate that the route of infection may be independent of bacteraemia. The documented direct communication between the nasal lymphatics and the subarachnoid space could provide a hypothesis explaining the pathophysiologic mechanisms of meningeal infection and overcoming all the limitations of the current theories. It could also explain the presence of negative blood cultures while meningeal inflammation is present. Furthermore, it could also interpret the occasional fulminating evolution of bacterial meningitis since intense host defenses and central nervous system barriers could be bypassed. In our current communication we examine the role of the nasal lymphatic pathway in the development of meningitis. It is apparent that better understanding of the infection and dissemination route for bacterial meningitis can provide the opportunity for a more effective treatment.

  9. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Barleon Bernhard

    2010-07-01

    Full Text Available Abstract Background Postnatal endothelial progenitor cells (EPCs have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated. Results In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels. Mouse lung microvascular endothelial cells (MLMVECs were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony. These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels. Conclusion The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.

  10. Evolutionary implications of the distribution and variation of the skeletal muscles of the anuran lymphatic system.

    Science.gov (United States)

    Drewes, Robert C; Hillman, Stanley S; Hedrick, Michael S; Withers, Philip C

    2013-01-01

    Lymphatic return to the circulation in anurans is dependent upon the interaction of a number of skeletal muscles and lung deflation. We define character states and describe variation of these putative lymphatic skeletal muscles: the M. cutaneus pectoris (CP), M. cutaneus dorsi (CD), M. piriformis (P), M. sphincter ani cloacalis (SAC), and the complex of the M. gracilis minor/M. abdominal crenator (GM/AC). We include examination of over 400 specimens of 377 species belonging to 40 of the 42 currently recognized anuran families. Some muscles show limited variation (P) or are clearly linked to phylogeny (CP; CD) and thus have limited value in the determination of form and function. However, the GM/AC and SAC show a high degree of structural variation that appears in taxa across the phylogenetic spectrum. This allows us to make phylogenetically independent determinations of form and function. We define an ancestral state of the GM and conclude that evolution of the GM/AC and SAC has progressed in two directions from this ancestral state: toward either elaboration or reduction. Where present, the character states of both of these muscle groups were observed in all species examined and the number of states correlated within each family as well. The degree of development of the GM/AC and SAC compliance pump system is strongly correlated with previously determined lymph flux rates in a three species test. Our data suggest there may be a relationship between greater elaboration of the GM/AC and SAC system and terrestriality among the Anura.

  11. Lessons from the Pacific programme to eliminate lymphatic filariasis: a case study of 5 countries

    Directory of Open Access Journals (Sweden)

    Huppatz Clare

    2009-06-01

    Full Text Available Abstract Background Lymphatic Filariasis (LF is an important Neglected Tropical Disease, being a major cause of disability worldwide. The Global Programme to Eliminate Lymphatic Filariasis aims to eliminate LF as a public health problem by the year 2020, primarily through repeated Mass Drug Administration (MDA. The Pacific region programme commenced in 1999. By June 2007, five of the eleven countries classified as endemic had completed five MDA campaigns and post-MDA prevalence surveys to assess their progress. We review available programme data and discuss their implications for other LF elimination programs in developing countries. Methods Reported MDA coverage and results from initial surveys and post-MDA surveys of LF using the immunochromatographic test (ICT from these five Pacific Island countries (Tonga, Niue, Vanuatu, Samoa and Cook Islands were analysed to provide an understanding of their quality and programme progress towards LF elimination. Denominator data reported by each country programme for 2001 was compared to official sources to assess the accuracy of MDA coverage data. Results Initial survey results from these five countries revealed an ICT prevalence of between 2.7 and 8.6 percent in individuals tested prior to commencement of the programme. Country MDA coverage results varied depending on the source of denominator data. Of the five countries in this case study, three countries (Tonga, Niue and Vanuatu reached the target prevalence of Conclusion Accurate and representative baseline and post-campaign prevalence data is crucial for determining program effectiveness and the factors contributing to effectiveness. This is emphasised by the findings of this case study. While three of the five Pacific countries reported achieving the target prevalence of

  12. Invasion of lymphatic vessels into the eye after open globe injuries.

    Science.gov (United States)

    Wessel, Julia M; Hofmann-Rummelt, Carmen; Kruse, Friedrich E; Cursiefen, Claus; Heindl, Ludwig M

    2012-06-20

    We analyzed whether lymphatic vessels can be detected in eyes enucleated after an open globe injury. The presence of lymphatic vessels was analyzed immunohistochemically using podoplanin as a specific lymphatic endothelial marker in 21 globes that had been enucleated after open globe injury. The localization of pathologic lymphatic vessels (within the eye wall or inside the eye) was correlated with the mechanism of trauma, anatomic site of perforation or rupture, and time interval between trauma and enucleation. Pathologic lymphatic vessels were detected in 15 of 21 eyes (71%) enucleated after an open globe injury. In 5 globes (24%) they were found within the eye, located in retrocorneal membranes, underneath the sclera, and adjacent to uveal tissue (ciliary body, iris). No significant association was observed between the presence of pathologic lymphatic vessels and the mechanism of trauma (P = 0.598), anatomic site of perforation or rupture (P = 0.303), and time interval between trauma and enucleation (P = 0.145). The human eye can be invaded secondarily by lymphatic vessels if the eye wall is opened by trauma. This mechanism could be important for wound healing, immunologic defense against intruding microorganisms, and autoimmune reactions against intraocular antigens.

  13. Efficacy of AdipoDren® in Reducing Interleukin-1-Induced Lymphatic Endothelial Hyperpermeability.

    Science.gov (United States)

    Ciccone, Valerio; Monti, Martina; Antonini, Giulia; Mattoli, Luisa; Burico, Michela; Marini, Francesca; Maidecchi, Anna; Morbidelli, Lucia

    2016-01-01

    Lymphatic leakage can be seen as a detrimental phenomenon associated with fluid retention and deposition as well as gain of weight. Moreover, lymphatic dysfunction is associated with an inflammatory environment and can be a substrate for other health conditions. A number of treatments can ameliorate lymphatic vasculature: natural substances have been used as treatment options particularly suitable for their consolidated effectiveness and safety profile. Here we report the protective effect of AdipoDren®, an association of a series of plant-derived natural complexes, on lymphatic endothelium permeability promoted by interleukin-1 beta (IL-1β) and the associated molecular mechanisms. AdipoDren® demonstrated a protective effect on dermal lymphatic endothelial cell permeability increased by IL-1β. Reduced permeability was due to the maintenance of tight junctions and cell-cell localisation of occludin and zonula occludens-1 (ZO-1). Moreover, AdipoDren® reduced the expression of the inflammatory key element cyclooxygenase-2 (COX-2), while not altering the levels of endothelial and inducible nitric oxide synthases (eNOS and iNOS). The upregulation of antioxidant enzymatic systems (catalase and superoxide dismutase-1, SOD-1) and the downregulation of pro-oxidant markers (p22 phox subunit of NADPH oxidase) were also evident. In conclusion, AdipoDren® would be useful to ameliorate conditions of altered lymphatic vasculature and to support the physiological functionality of the lymphatic endothelium.