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Sample records for experimental lymphatic vascular

  1. 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.

  2. Diagnosis and Management of Lymphatic Vascular Disease

    National Research Council Canada - National Science Library

    Rockson, Stanley G

    2008-01-01

    ... it. The most readily recognizable attribute of lymphatic vascular incompetence is the presence of the characteristic swelling of tissues, called lymphedema, which arises as a consequence of insufficient lymph transport...

  3. The lymphatic vascular system of the mouse head

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    Lohrberg, Melanie; Wilting, Jörg

    2016-01-01

    Histological studies of the lymphatic vascular system in adult mice are hampered because bones cannot be sectioned properly. Here, we decalcified the heads of 14-day-old mice, embedded them in paraffin and stained resultant serial sections with the lymphendothelial-specific antibodies Lyve-1 and Podoplanin. We show that the tissues with the highest lymphatic vascular density are the dermis and the oral mucous membranes. In contrast, the nasal mucous membrane is devoid of lymphatics, except fo...

  4. [Lymphatic vascular pathologies: contribution of lympho-fluoroscopy].

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    Tomson, Didier; Lessert, Claudia; Luthi, Irène; Mazzolai, Lucia; Depairon, Michèle

    2015-02-04

    If clinical examination has an essential importance in lymphology disorders and requires experimented practitioners, lymphoscintigraphy and more recently green indocyanine lympho-fluoroscopy constitute precious complementary investigations in prevention, diagnosis, and treatment of lymphatic vascular pathologies. The lymphoscintigraphy interest lies in qualitative and quantitative analysis of macromolecules migration within lymphatic vessels and the deep lymphatic network. The lympho-fluoroscopy distinguishes itself from lymphoscintigraphy allowing real time superficial lymphatic vessels detailed mapping, gathering important information on their contractility, and the presence of compensatory derivations to be favored during manual lymphatic drainage to angiologist and physiotherapist.

  5. Inflammatory manifestations of experimental lymphatic insufficiency.

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    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.

  6. The lymphatic vascular system of the mouse head.

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    Lohrberg, Melanie; Wilting, Jörg

    2016-12-01

    Histological studies of the lymphatic vascular system in adult mice are hampered because bones cannot be sectioned properly. Here, we decalcified the heads of 14-day-old mice, embedded them in paraffin and stained resultant serial sections with the lymphendothelial-specific antibodies Lyve-1 and Podoplanin. We show that the tissues with the highest lymphatic vascular density are the dermis and the oral mucous membranes. In contrast, the nasal mucous membrane is devoid of lymphatics, except for its most basal parts below the vomeronasal organ. The inferior nasal turbinate contains numerous lymphatics and is connected to the nasolacrimal duct (NLD), which is ensheathed by a dense network of lymphatics. The lymphatics of the eye lids and conjunctiva are connected to those of the inferior nasal turbinate. We suggest that cerebro-spinal fluid (CSF) can drain via the optic nerve and NLD lymphatics, whereas CSF drained via the Fila olfactoria into the nasal mucous membrane is used for moisturization of the respiratory air. Tongue, palatine and buccal mucous membranes possess numerous lymphatics, whereas the dental pulp has none. Lymphatics are present in the maxillary gland and close to the temporomandibular joint, suggesting the augmentation of lymph flow by chewing and yawning. Lymphatics can also be found in the dura mater and in the dural septae entering into deeper parts of the brain. Our findings are discussed with regard to CSF drainage and potential routes for ocular tumor dissemination.

  7. 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

  8. Crosslinking of collagen scaffolds promotes blood and lymphatic vascular stability.

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    Chan, Kelvin L S; Khankhel, Aimal H; Thompson, Rebecca L; Coisman, Brent J; Wong, Keith H K; Truslow, James G; Tien, Joe

    2014-09-01

    The low stiffness of reconstituted collagen hydrogels has limited their use as scaffolds for engineering implantable tissues. Although chemical crosslinking has been used to stiffen collagen and protect it against enzymatic degradation in vivo, it remains unclear how crosslinking alters the vascularization of collagen hydrogels. In this study, we examine how the crosslinking agents genipin and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide alter vascular stability and function in microfluidic type I collagen gels in vitro. Under moderate perfusion (∼10 dyn/cm(2) shear stress), tubes of blood endothelial cells (ECs) exhibited indistinguishable stability and barrier function in untreated and crosslinked scaffolds. Surprisingly, under low perfusion (∼5 dyn/cm(2) shear stress) or nearly zero transmural pressure, microvessels in crosslinked scaffolds remained stable, while those in untreated gels rapidly delaminated and became poorly perfused. Similarly, tubes of lymphatic ECs under intermittent flow were more stable in crosslinked gels than in untreated ones. These effects correlated well with the degree of mechanical stiffening, as predicted by analysis of fracture energies at the cell-scaffold interface. This work demonstrates that crosslinking of collagen scaffolds does not hinder normal EC physiology; instead, crosslinked scaffolds promote vascular stability. Thus, routine crosslinking of scaffolds may assist in vascularization of engineered tissues. © 2013 Wiley Periodicals, Inc.

  9. 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

  10. Polypoid vascular and lymphatic malformation of the duodenum: a case report.

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    Kim, Jeong Wook; Oh, Hyoung Chul; Kim, Mi Kyung; Kim, Jae Gyu

    2010-03-01

    Polypoid vascular and lymphatic malformation of the small intestine is rare. We report the case of a polypoid vascular and lymphatic malformation of the duodenum in a 58-year-old woman presenting with post-prandial epigastric discomfort. She did not have common symptoms of intestinal vascular and lymphatic malformation, such as gastrointestinal bleeding, steatorrhea, and hypoalbuminemia. A 5.0x0.8-cm semipedunculated polypoid lesion was found in the duodenal bulb with protrusion into the prepyloric antrum and was successfully removed using an endoscopic snare.

  11. Zebrafish provides a novel model for lymphatic vascular research

    NARCIS (Netherlands)

    Karpanen, T.; Schulte-Merker, S.

    2011-01-01

    The mammalian lymphatic vasculature has an important function in the maintenance of tissue fluid homeostasis, absorption of dietary lipids, and immune surveillance. The lymphatic vessels are also recruited by many tumors as primary routes for metastasis and mediate immune responses in inflammatory

  12. Pkd1 regulates lymphatic vascular morphogenesis during development

    NARCIS (Netherlands)

    Coxam, Baptiste; Sabine, Amélie; Bower, Neil I; Smith, Kelly A; Pichol-Thievend, Cathy; Skoczylas, Renae; Astin, Jonathan W; Frampton, Emmanuelle; Jaquet, Muriel; Crosier, Philip S; Parton, Robert G; Harvey, Natasha L; Petrova, Tatiana V; Schulte-Merker, Stefan; Francois, Mathias; Hogan, Benjamin M

    2014-01-01

    Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration,

  13. Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer

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    Kim Wun-Jae

    2011-04-01

    Full Text Available Abstract Background Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet the relationship between lymphangiogenesis and lymphatic metastasis is not well known. The aim of this study is to elucidate underlying mechanisms of how expanded lymphatic vessels and tumor microenvironment interacts each other and to find effective therapeutic options to inhibit lymphatic metastasis. Results The orthotopic urinary bladder cancer (OUBC model was generated by intravesical injection of MBT-2 cell lines. We investigated the angiogenesis, lymphangiogenesis, and CD11b+/CD68+ tumor-associated macrophages (TAM by using immunofluorescence staining. OUBC displayed a profound lymphangiogenesis and massive infiltration of TAM in primary tumor and lymphatic metastasis in lymph nodes. TAM flocked near lymphatic vessels and express higher levels of VEGF-C/D than CD11b- cells. Because VEGFR-3 was highly expressed in lymphatic vascular endothelial cells, TAM could assist lymphangiogenesis by paracrine manner in bladder tumor. VEGFR-3 expressing adenovirus was administered to block VEGF-C/D signaling pathway and clodronate liposome was used to deplete TAM. The blockade of VEGF-C/D with soluble VEGF receptor-3 markedly inhibited lymphangiogenesis and lymphatic metastasis in OUBC. In addition, the depletion of TAM with clodronate liposome exerted similar effects on OUBC. Conclusion VEGF-C/D are the main factors of lymphangiogenesis and lymphatic metastasis in bladder cancer. Moreover, TAM plays an important role in these processes by producing VEGF-C/D. The inhibition of lymphangiogenesis could provide another therapeutic target to inhibit lymphatic metastasis and recurrence in patients with invasive bladder cancer.

  14. miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo

    NARCIS (Netherlands)

    Pedrioli, D.M.; Karpanen, T.; Dabouras, V.; Jurisic, G.; van de Hoek, G.; Shin, J.W.; Marino, D.; Kalin, R.E.; Leidel, S.; Cinelli, P.; Schulte-Merker, S.; Brandli, A.W.; Detmar, M.

    2010-01-01

    The lymphatic vascular system maintains tissue fluid homeostasis, helps mediate afferent immune responses, and promotes cancer metastasis. To address the role microRNAs (miRNAs) play in the development and function of the lymphatic vascular system, we defined the in vitro miRNA expression profiles

  15. Conserved signaling through vascular endothelial growth (VEGF) receptor family members in murine lymphatic endothelial cells.

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    Coso, Sanja; Zeng, Yiping; Sooraj, Dhanya; Williams, Elizabeth D

    2011-10-15

    Lymphatic vessels guide interstitial fluid, modulate immune responses by regulating leukocyte and antigen trafficking to lymph nodes, and in a cancer setting enable tumor cells to track to regional lymph nodes. The aim of the study was to determine whether primary murine lymphatic endothelial cells (mLECs) show conserved vascular endothelial growth factor (VEGF) signaling pathways with human LECs (hLECs). LECs were successfully isolated from murine dermis and prostate. Similar to hLECs, vascular endothelial growth factor (VEGF) family ligands activated MAPK and pAkt intracellular signaling pathways in mLECs. We describe a robust protocol for isolation of mLECs which, by harnessing the power of transgenic and knockout mouse models, will be a useful tool to study how LEC phenotype contributes to alterations in lymphatic vessel formation and function. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  16. Lymphatic anatomy of the inguinal region in aid of vascularized lymph node flap harvesting.

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    Scaglioni, Mario F; Suami, Hiroo

    2015-03-01

    Vascularized lymph node transfer (VLNT) has shown promise as a treatment for breast cancer-related lymphedema, a common and debilitating condition among breast cancer survivors. In VLNT, the most popular lymph node flap donor site is the inguinal region; however, concerns about the possibility of iatrogenic lymphedema hamper the widespread adoption of VLNT. A better understanding of the anatomy of the lymphatic system in the inguinal region is essential to preserving lymph drainage in the leg and avoiding iatrogenic lymphedema. Five human cadaver hind-quarter specimens were used for this study. First, the specimens were scanned with indocyanine green fluorescence lymphography to map the lymphatic vessels. A dual injection technique using different radiocontrast media was then applied to delineate arteries and lymphatic vessels on radiographs. Finally, radiological analysis and meticulous dissection were used to investigate relationships between the arteries and lymphatic vessels. By chasing the lymphatic vessels retrogradely from their corresponding lymph nodes, we were able to divide the superficial inguinal lymph nodes into three subgroups: the abdominal, medial thigh, and lateral thigh nodes. We found no connections between the superficial and deep lymphatic system in the inguinal region. The dominant lymph nodes draining the leg were in the lower part of the inguinal triangle, and their efferent lymphatic vessels ran medial to the common femoral artery. Preserving the sentinel nodes of the lower leg in the medial thigh and their efferent lymphatic vessels is crucial to avoid iatrogenic lymphedema in limbs with donor sites for VLNT. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Crosslinking of collagen scaffolds promotes blood and lymphatic vascular stability

    OpenAIRE

    Chan, Kelvin L.S.; Khankhel, Aimal H.; Thompson, Rebecca L.; Coisman, Brent J.; Wong, Keith H.K.; Truslow, James G.; Tien, Joe

    2013-01-01

    The low stiffness of reconstituted collagen hydrogels has limited their use as scaffolds for engineering implantable tissues. Although chemical crosslinking has been used to stiffen collagen and protect it against enzymatic degradation in vivo, it remains unclear how crosslinking alters the vascularization of collagen hydrogels. In this study, we examine how the crosslinking agents genipin and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) alter vascular stability and function in microf...

  18. Prognostic significance of vascular and lymphatic emboli in resected pulmonary adenocarcinoma.

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    Strano, Salvatore; Lupo, Audrey; Lococo, Filippo; Schussler, Olivier; Loi, Mauro; Younes, Mohamad; Bobbio, Antonio; Damotte, Diane; Regnard, Jean-François; Alifano, Marco

    2013-04-01

    The incidence of vascular and lymphatic emboli in a specimen of resected non-small cell lung cancer is variable according to different authors' experience as well as prognostic significance in patients treated by surgery. We aimed at evaluating these factors in an unselected population of patients with primary pulmonary adenocarcinoma treated by major surgical resection. Clinical and pathology records of all patients treated by lobectomy or pneumonectomy and nodal dissection for pulmonary adenocarcinoma between June 2001 and June 2006 were retrospectively reviewed. Impact on survival of age, sex, tobacco use, history of chronic obstructive pulmonary disease, extent of resection, pathologic stage, and presence of vascular and lymphatic emboli was studied by univariate analysis and multivariate analysis (for factors significantly associated with survival at univariate analysis). Five hundred three patients underwent lobectomy or pneumonectomy with nodal dissection for pathologically proven lung adenocarcinoma. There were 355 men and 148 women; mean age was 61.1 years, and 181 patients were 65 years old or older; 87% were current or former smokers; 90.3% had pulmonary lobectomy; and 9.7% had pneumonectomy. Pathologic stages were I, II, and III/IV in 45%, 17.9%, and 37.1%, respectively. Vascular emboli and lymphatic emboli were found in 183 of 503 patients (36.4%) and 149 of 503 (29.6%), respectively. Overall 5-year survival for the whole population was 50.7%. At univariate analysis, age more than 65 years (p=0.0019), chronic obstructive pulmonary disease (p=0.042), extent of resection (p=0.047), pathologic stage (p<0.0000001), T size (p=0.0020), T and N variables (p=0.0000016 and p<0.0000001, respectively), presence of vascular emboli (p=0.026), and presence of lymphatic emboli (p=0.000021) were associated with worse prognosis. At multivariate analysis, age more than 65 years (p=0.0047, relative risk 1.5), stage I versus II versus III versus IV (p=0.00000032), and

  19. A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development.

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    Villefranc, Jacques A; Nicoli, Stefania; Bentley, Katie; Jeltsch, Michael; Zarkada, Georgia; Moore, John C; Gerhardt, Holger; Alitalo, Kari; Lawson, Nathan D

    2013-04-01

    Vascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized. Here, we identify a mutation in zebrafish vegfc that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic backgrounds. The um18 mutation prematurely truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, vegfc(um18) could not rescue lymphatic defects in mutant embryos, but induced ectopic blood vessel branching. Furthermore, vegfc-deficient endothelial cells did not efficiently contribute to tip cell positions in developing sprouts. Computational modeling together with assessment of endothelial cell dynamics by time-lapse analysis suggested that an autocrine Vegfc/Flt4 loop plays an important role in migratory persistence and filopodia stability during sprouting. Our results suggest that Vegfc acts in two distinct modes during development: as a paracrine factor secreted from arteries to guide closely associated lymphatic vasculature and as an autocrine factor to drive migratory persistence during angiogenesis.

  20. 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.

  1. 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.

  2. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

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    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A.; Tsunoda, Ikuo

    2015-01-01

    Background: Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2(+/−) mice would influence the course of disease in a model of experimental colitis. Methods: Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2(+/−) mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. Results: We found that FoxC2 downregulation in FoxC2(+/−) mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. Conclusions: These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease. PMID:25822012

  3. Downregulation of FoxC2 Increased Susceptibility to Experimental Colitis: Influence of Lymphatic Drainage Function?

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    Becker, Felix; Potepalov, Sergey; Shehzahdi, Romana; Bernas, Michael; Witte, Marlys; Abreo, Fleurette; Traylor, James; Orr, Wayne A; Tsunoda, Ikuo; Alexander, Jonathan Steven

    2015-06-01

    Although inflammation-induced expansion of the intestinal lymphatic vasculature (lymphangiogenesis) is known to be a crucial event in limiting inflammatory processes, through clearance of interstitial fluid and immune cells, considerably less is known about the impact of an impaired lymphatic clearance function (as seen in inflammatory bowel diseases) on this cascade. We aimed to investigate whether the impaired intestinal lymphatic drainage function observed in FoxC2 mice would influence the course of disease in a model of experimental colitis. Acute dextran sodium sulfate colitis was induced in wild-type and haploinsufficient FoxC2 mice, and survival, disease activity, colonic histopathological injury, neutrophil, T-cell, and macrophage infiltration were evaluated. Functional and structural changes in the intestinal lymphatic vessel network were analyzed, including submucosal edema, vessel morphology, and lymphatic vessel density. We found that FoxC2 downregulation in FoxC2 mice significantly increased the severity and susceptibility to experimental colitis, as displayed by lower survival rates, increased disease activity, greater histopathological injury, and elevated colonic neutrophil, T-cell, and macrophage infiltration. These findings were accompanied by structural (dilated torturous lymphatic vessels) and functional (greater submucosal edema, higher immune cell burden) changes in the intestinal lymphatic vasculature. These results indicate that sufficient lymphatic clearance plays a crucial role in limiting the initiation and perpetuation of experimental colitis and those disturbances in the integrity of the intestinal lymphatic vessel network could intensify intestinal inflammation. Future therapies might be able to exploit these processes to restore and maintain adequate lymphatic clearance function in inflammatory bowel disease.

  4. 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

  5. Experimental ileitis alters prostaglandin biosynthesis in mesenteric lymphatic and blood vessels.

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    Rehal, Sonia; von der Weid, Pierre-Yves

    2015-01-01

    Prostaglandins are important mediators responsible for many changes that occur during the inflammatory response. Specifically, in inflammatory bowel disease (IBD), prostaglandins are key players in maintenance of blood flow and mucosal defense. In blood vessels, prostaglandins modulate and inhibit transmigration. In lymphatic vessels, on the other hand, prostaglandin E2 (PGE2) and prostacyclin (PGI2) have been shown to potently inhibit lymphatic contractility. Inhibition of lymphatic contractility could impair proper tissue fluid drainage during inflammation, consequently leading to the submucosal oedema observed in IBD. Alterations in production of PGE2 and PGI2 during inflammation could have severe implications on lymphatic and vascular functions within the small intestine. Using the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis guinea pig and rat models, we assessed by quantitative PCR changes in mRNA transcript of enzymes and receptors involved in the production and actions of prostaglandins in mesenteric lymphatic and blood vessels as well as in the affected ileum. Furthermore, we also assessed lymphatic tissue levels of PGE2 and PGI2 during inflammation. We observed significant changes in lymphatic mRNA expression of COX-1, COX-2, MPGES-1, PGIS, EP4 and IP and increases in PGE2 and PGI2 in tissues of TNBS-treated animals. Changes in mRNA in blood vessels from TNBS-treated animals included differences in COX-1, COX-2, MPGES-1, PGIS, EP1, EP2 and IP expression. Prostaglandin metabolites are differentially regulated in both lymphatic and blood vessels during intestinal inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic System and Lymphangiogenesis.

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    Hayashida, Kenji; Yoshida, Shuhei; Yoshimoto, Hiroshi; Fujioka, Masaki; Saijo, Hiroto; Migita, Kiyoshi; Kumaya, Misato; Akita, Sadanori

    2017-03-01

    Secondary lymphedema is often observed in postmalignancy treatment of the breast and the gynecologic organs, but effective therapies have not been established in chronic cases even with advanced physiologic operations. Currently, reconstructive surgery with novel approaches has been attempted. The hindlimbs of 10-week-old male C57BL/6J mice, after 30-Gy x-irradiation, surgical lymph node dissection, and 5-mm gap creation, were divided into four groups, with vascularized lymph node transfer abdominal flap and 1.0 × 10 adipose-derived stem cells. Lymphatic flow assessment, a water-displacement plethysmometer paw volumetry test, tissue quantification of lymphatic vessels, and functional analysis of lymphatic vessels and nodes were performed. Photodynamic Eye images, using indocyanine green fluorescence, demonstrated immediate staining in subiliac lymph nodes, and linear pattern imaging of the proximal region was observed with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer. Both percentage improvement and percentage deterioration with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer were significantly better than with other treatments (p lymphatic vessels with LYVE-1 immunoreactivity significantly increased in mice treated with adipose-derived stem cells (p lymphatic vessels and vascularized lymph node transfers induce the lymphatic flow drainage to the circulatory system. Combined adipose-derived stem cell and vascularized lymph node transfer treatment in secondary lymphedema may effectively decrease edema volume and restore lymphatic function by lymphangiogenesis and the lymphatic-to-venous circulation route.

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

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    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.

  8. Short time effects of radiotherapy on lymphatic vessels and restorative lymphatic pathways: experimental approaches ina mouse model.

    Science.gov (United States)

    Pastouret, F; Lievens, P; Leduc, O; Bourgeois, P; Tournel, K; Lamote, J; Zirak, C; Leduc, A

    2014-06-01

    Radiotherapy (RT) is an important component in the therapeutic approach to oncologic conditions. This study presents the investigative results on the impact of RT on lymphatic vessels and on the regenerative response of the lymphatic system in a mouse model. We first irradiated 3 groups of ten mice using brachytherapy in a single treatment of 20 Gy. We then performed morphological examination of the irradiated lymphatic vessels using an in vivo microscopic transillumination technique at 2, 4, and 6 weeks. Next we evaluated lymphatic flow using lymphoscintigraphy and in vivo microscopy at 6 to 11 weeks in: 10 additional mice following irradiation as above (IR), in 10 mice following incision of a lymphatic vessel (I), and in a non-treated control group of 10 mice (N). Intact lymphatic vessels were observed in all mice at 2, 4, and 8 weeks following the single dose of radiotherapy in the first group of mice and normal lymphatic flow was fully restored in the irradiated (IR) and incised (I) mice indicating that the reparative substitution lymphatic pathways are functioning normally. We found that following irradiation with one dose of 20 Gy, lymphatic vessels were not visibly damaged and also that lymphatic flow was consistently restored and substitutive lymphatic pathways formed.

  9. Clarifications Regarding the Topographical Location of the Vascular, Lymphatic and Nervous Formations from the Thorax Aperture in Dog

    Directory of Open Access Journals (Sweden)

    Carmen Berghes

    2010-05-01

    Full Text Available Our studies are intended to bring some clarification on the topographic situation of lymphatic vascular and nerve formations in the thoracic aperture to the dog. Data from the literature are less relevant because the other factions by surprise earlier in the mediastinum without to make a correlation between them [6, 7, 8]. The study was performed on 20 corpses of dog different breeds, ages and gender. Vascular formations were injected with a mixture prepare the laboratory of anatomy of the discipline. Photographic paper presents several models dissected setting with as much precision topographic situation of the anatomical formations and has a highly application in human medicine, bringing clarification on topography thoracic duct lymph in the large vessels transport underlying heart. Lymphatic ducts is attached the entire length of the front right mediastinal aorta. That is opening in cranial vena cava without having a secundar channel.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Therapeutic efficacy of vacuum-assisted-closure therapy in the treatment of lymphatic complications following peripheral vascular interventions and surgeries.

    Science.gov (United States)

    Aydin, Ufuk; Gorur, Alper; Findik, Orhan; Yildirim, Abdullah; Kocogullari, Cevdet Ugur

    2015-02-01

    Lymphatic complications, lymphocele and lymphorrhea being the leading, are generally encountered after vascular interventions and surgeries. The present study aimed to evaluate the outcomes of vacuum-assisted-closure (VAC) therapy, which we frequently prefer as the first-choice treatment for such complications. Among patients undergoing peripheral vascular intervention or surgery between January 2008 and February 2012, the medical files of 21 patients who received VAC therapy or other treatment due to symptomatic lymphatic complications were retrospectively analyzed and the results were discussed. Group I consisted of 10 patients (three with lymphocele and seven with lymphorrhea) who underwent VAC therapy as the first-choice treatment, Group II consisted of 11 patients of which 7 patients received various therapies before VAC therapy and 4 patients received other treatments alone. The patients who received VAC therapy as the primary therapy demonstrated more rapid wound healing, early drainage control, and shorter hospital stay. The mean hospital medical cost was €1038 (range, €739-1826) for the patients who primarily underwent VAC therapy; it was calculated to be €2137 (range, €1610-3130) for the other patients (p=0.001). In addition to its safety and good clinical outcomes, VAC therapy also has economic advantages and should be the primary method for the treatment of lymphatic complications. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. 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

    2015-01-01

    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. PMID:26077718

  13. 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. © 2015 Aspelund et al.

  14. 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.

  15. The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas.

    Science.gov (United States)

    Zorgetto, Verônica A; Silveira, Giórgia G; Oliveira-Costa, João Paulo; Soave, Danilo F; Soares, Fernando A; Ribeiro-Silva, Alfredo

    2013-10-18

    Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors. Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ≤ 0.05 were considered significant. In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we

  16. 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.

  17. Development of the larval lymphatic system in zebrafish.

    Science.gov (United States)

    Jung, Hyun Min; Castranova, Daniel; Swift, Matthew R; Pham, Van N; Venero Galanternik, Marina; Isogai, Sumio; Butler, Matthew G; Mulligan, Timothy S; Weinstein, Brant M

    2017-06-01

    The lymphatic vascular system is a hierarchically organized complex network essential for tissue fluid homeostasis, immune trafficking and absorption of dietary fats in the human body. Despite its importance, the assembly of the lymphatic network is still not fully understood. The zebrafish is a powerful model organism that enables study of lymphatic vessel development using high-resolution imaging and sophisticated genetic and experimental manipulation. Although several studies have described early lymphatic development in the fish, lymphatic development at later stages has not been completely elucidated. In this study, we generated a new Tg(mrc1a:egfp)(y251) transgenic zebrafish that uses a mannose receptor, C type 1 (mrc1a) promoter to drive strong EGFP expression in lymphatic vessels at all stages of development and in adult zebrafish. We used this line to describe the assembly of the major vessels of the trunk lymphatic vascular network, including the later-developing collateral cardinal, spinal, superficial lateral and superficial intersegmental lymphatics. Our results show that major trunk lymphatic vessels are conserved in the zebrafish, and provide a thorough and complete description of trunk lymphatic vessel assembly. © 2017. Published by The Company of Biologists Ltd.

  18. Abdominal lymphatic malformation: Spectrum of imaging findings

    OpenAIRE

    Anupam Lal; Pankaj Gupta; Manphool Singhal; Saroj K Sinha; Sadhana Lal; Surinder Rana; Niranjan Khandelwal

    2016-01-01

    Lymphatic malformations are congenital vascular malformations with lymphatic differentiation. Although the most common locations for lymphatic malformation are the neck and axilla, they can occur at several locations in the body including the abdomen. The abdominal location is rather rare and accounts for approximately 5% of all lymphatic malformation. Abdominal lymphatic malformation can arise from mesentery, omentum, gastrointestinal tract, and retroperitoneum. Clinical presentation include...

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

    OpenAIRE

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

  20. Curative effect of paclitaxel and cisplatin combined chemotherapy on cervical cancer and its relation with tissue micro vascular and lymphatic vessels density.

    Science.gov (United States)

    Gao, Zhi-Hui; Wang, Qian-Qing

    2015-09-01

    This study was to discuss the curative effect of paclitaxel and cisplatin combined chemotherapy on cervical cancer and its relation with tissue micro vascular and lymphatic vessels density. The combined chemotherapy of paclitaxel 135 mg/m² and cisplatin 25mg/m² were taken to observe the clinical curative effect. The postoperative paraffin tissue had been collected, had performed the LYVE-1 (lymphatic endothelium specific hyaluronan receptor-1) and CD31 immunohistochemical staining. The complete remission rate of high micro lymphatic vessels density group (was or more 6.0) and high micro vascular density group were obviously higher than in low micro lymphatic vessels density group and low micro vascular density group, the difference was statistically significance (P<0.05). This study further analyzed the relation of MVD and LVD with clinical pathological parameters. The difference was statistically significant (P<0.01). The curative effect of paclitaxel and cisplatin combined therapy was promising, positive and was closely related with cervical cancer tissue LVD and MVD. The LVD and MVD could be one of the predictors of early cervical CIN and early cervical cancer development.

  1. Lymphatic Disorders

    Science.gov (United States)

    ... blood from the upper body into the heart. Lymphatic System: Helping Defend Against Infection The lymphatic system ... the neck, armpits, and groin. Disorders of the lymphatic system The lymphatic system may not carry out ...

  2. Kaposin-B enhances the PROX1 mRNA stability during lymphatic reprogramming of vascular endothelial cells by Kaposi's sarcoma herpes virus.

    Directory of Open Access Journals (Sweden)

    Jaehyuk Yoo

    2010-08-01

    Full Text Available Kaposi's sarcoma (KS is the most common cancer among HIV-positive patients. Histogenetic origin of KS has long been elusive due to a mixed expression of both blood and lymphatic endothelial markers in KS tumor cells. However, we and others discovered that Kaposi's sarcoma herpes virus (KSHV induces lymphatic reprogramming of blood vascular endothelial cells by upregulating PROX1, which functions as the master regulator for lymphatic endothelial differentiation. Here, we demonstrate that the KSHV latent gene kaposin-B enhances the PROX1 mRNA stability and plays an important role in KSHV-mediated PROX1 upregulation. We found that PROX1 mRNA contains a canonical AU-rich element (ARE in its 3'-untranslated region that promotes PROX1 mRNA turnover and that kaposin-B stimulates cytoplasmic accumulation of the ARE-binding protein HuR through activation of the p38/MK2 pathway. Moreover, HuR binds to and stabilizes PROX1 mRNA through its ARE and is necessary for KSHV-mediated PROX1 mRNA stabilization. Together, our study demonstrates that kaposin-B plays a key role in PROX1 upregulation during lymphatic reprogramming of blood vascular endothelial cells by KSHV.

  3. Lymphatic vascular invasion in ovarian serous tumors of low malignant potential with stromal microinvasion: a case control study.

    Science.gov (United States)

    Sangoi, Ankur R; McKenney, Jesse K; Dadras, Soheil S; Longacre, Teri A

    2008-02-01

    Stromal microinvasion in ovarian serous tumors of low malignant potential (S-LMP) stratifies patients at long-term risk for disease progression independent of stage and primary ovarian histology. Despite the histologic impression and often-quoted incidence of lymphatic vascular invasion (LVI) in S-LMP with stromal microinvasion, there has been no formal evaluation in a case control series of S-LMP. The presence and extent of (LVI) was assessed in 20 S-LMP with stromal microinvasion and 20 S-LMP case controls without stromal microinvasion and compared with a series of low-grade and high-grade serous carcinomas using D2-40 monoclonal antibody recognizing podoplanin, a novel lymphatic endothelial marker. S-LMP case controls were matched for primary ovarian histology (usual vs. micropapillary), International Federation of Gynecology and Obstetrics (FIGO) stage, and age (best possible match). The patterns of stromal microinvasion included individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, and inverted macropapillae. Immunohistologic staining with D2-40 monoclonal antibody clearly identified intratumoral LVI in 12/20 (60%) S-LMP with stromal microinvasion and 0/20 S-LMP without stromal microinvasion. Although only 4/13 (31%) low-grade serous carcinomas and 7/20 (35%) high-grade serous carcinomas had intratumoral LVI, hilar LVI was more common in the carcinomas (15% low-grade; 69% high-grade). Intratumoral LVI in S-LMP ranged from focal (6 cases) to multifocal (6 cases, maximum of 5 discrete foci) in any 1 section and included isolated single cells, simple papillae, and in 1 case, cribriform glands. Multifocal LVI was identified in 1 study patient who was pregnant. One of the 12 S-LMP patients with LVI had an intra-abdominal recurrence with high-grade disease at 16 months; whereas all other patients with follow-up were free of disease. LVI in ovarian S-LMP was significantly associated with the presence of stromal

  4. Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function.

    Science.gov (United States)

    Meens, Merlijn J; Kutkut, Issa; Rochemont, Viviane; Dubrot, Juan; Kaladji, Fouad R; Sabine, Amélie; Lyons, Oliver; Hendrikx, Stefanie; Bernier-Latmani, Jeremiah; Kiefer, Friedemann; Smith, Alberto; Hugues, Stéphanie; Petrova, Tatiana V; Kwak, Brenda R

    2017-01-01

    Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency. Cx47 is dispensable for long-chain fatty acid absorption from the gut but rather promotes serum lipid handling as prolonged elevated triglyceride levels were observed in Cx47-deficient mice after oral lipid tolerance tests. When crossed with Apolipoprotein E-deficient (Apoe-/-) mice, LDL-cholesterol was decreased in young Cx47-/-Apoe-/- adults as compared to Apoe-/- mice, which was inverted later in life. Finally, advanced atherosclerotic plaques in thoracic-abdominal aortas of 15 months-old mice tended to be larger in Cx47-/-Apoe-/- mice. These plaques contained fewer macrophages but similar amounts of T lymphocytes, collagen and lipids than plaques of Apoe-/- mice. In conclusion, Cx47 is expressed in lymphatic endothelium and seems modestly implicated in multiple aspects of lymphatic pathophysiology.

  5. Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.

    Directory of Open Access Journals (Sweden)

    Krishnakumar Kizhatil

    2014-07-01

    Full Text Available Schlemm's canal (SC plays central roles in ocular physiology. These roles depend on the molecular phenotypes of SC endothelial cells (SECs. Both the specific phenotype of SECs and development of SC remain poorly defined. To allow a modern and extensive analysis of SC and its origins, we developed a new whole-mount procedure to visualize its development in the context of surrounding tissues. We then applied genetic lineage tracing, specific-fluorescent reporter genes, immunofluorescence, high-resolution confocal microscopy, and three-dimensional (3D rendering to study SC. Using these techniques, we show that SECs have a unique phenotype that is a blend of both blood and lymphatic endothelial cell phenotypes. By analyzing whole mounts of postnatal mouse eyes progressively to adulthood, we show that SC develops from blood vessels through a newly discovered process that we name "canalogenesis." Functional inhibition of KDR (VEGFR2, a critical receptor in initiating angiogenesis, shows that this receptor is required during canalogenesis. Unlike angiogenesis and similar to stages of vasculogenesis, during canalogenesis tip cells divide and form branched chains prior to vessel formation. Differing from both angiogenesis and vasculogenesis, during canalogenesis SECs express Prox1, a master regulator of lymphangiogenesis and lymphatic phenotypes. Thus, SC development resembles a blend of vascular developmental programs. These advances define SC as a unique vessel with a combination of blood vascular and lymphatic phenotypes. They are important for dissecting its functions that are essential for ocular health and normal vision.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Low-Flow Vascular Malformation Pitfalls: From Clinical Examination to Practical Imaging Evaluation--Part 1, Lymphatic Malformation Mimickers.

    Science.gov (United States)

    White, Candace L; Olivieri, Brandon; Restrepo, Ricardo; McKeon, Brett; Karakas, S Pinar; Lee, Edward Y

    2016-05-01

    Palpable subcutaneous masses present in various shapes and sizes in the pediatric population and, accordingly, represent a variety of underlying causes. Lymphatic and venous malformations are among the most common pediatric subcutaneous lesions. However, there are congenital and acquired, as well as benign and malignant, soft-tissue masses that can mimic them clinically and at imaging. Here, we review the natural history, wide range of clinical presentations, and varied but characteristic imaging appearance of lymphatic malformations that can pose diagnostic difficulties in children. In addition, the clinical and imaging characteristics of some pediatric soft-tissue pathologies that can mimic lymphatic malformations and clues to reach a proper diagnosis are highlighted.

  8. 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.

  9. Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

    OpenAIRE

    Wu, June K.; Christopher Kitajewski; Maia Reiley; Keung, Connie H.; Julie Monteagudo; Andrews, John P.; Peter Liou; Arul Thirumoorthi; Alvin Wong; Kandel, Jessica J; Shawber, Carrie J.

    2015-01-01

    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...

  10. Prostaglandin D2 regulates CD4+ memory T cell trafficking across blood vascular endothelium and primes these cells for clearance across lymphatic endothelium.

    Science.gov (United States)

    Ahmed, S Rumel; McGettrick, Helen M; Yates, Clara M; Buckley, Christopher D; Ratcliffe, Marianne J; Nash, Gerard B; Rainger, G Ed

    2011-08-01

    Memory lymphocytes support inflammatory and immune responses. To do this, they enter tissue via blood vascular endothelial cells (BVEC) and leave tissue via lymphatic vascular endothelial cells (LVEC). In this study, we describe a hierarchy of signals, including novel regulatory steps, which direct the sequential migration of human T cells across the blood and the lymphatic EC. Cytokine-stimulated (TNF and IFN) human BVEC preferentially recruited memory T cells from purified PBL. Lymphocyte recruitment from flow could be blocked using a function-neutralizing Ab against CXCR3. However, a receptor antagonist directed against the PGD(2) receptor DP2 (formerly chemoattractant receptor-homologous molecule expressed on Th2 cells) inhibited transendothelial migration, demonstrating that the sequential delivery of the chemokine and prostanoid signals was required for efficient lymphocyte recruitment. CD4(+) T cells recruited by BVEC migrated with significantly greater efficiency across a second barrier of human LVEC, an effect reproduced by the addition of exogenous PGD(2) to nonmigrated cells. Migration across BVEC or exogenous PGD(2) modified the function, but not the expression, of CCR7, so that chemotaxis toward CCL21 was significantly enhanced. Thus, chemokines may not regulate all stages of lymphocyte migration during inflammation, and paradigms describing their trafficking may need to account for the role of PGD(2).

  11. Cholinergic innervation of human mesenteric lymphatic vessels.

    Science.gov (United States)

    D'Andrea, V; Bianchi, E; Taurone, S; Mignini, F; Cavallotti, C; Artico, M

    2013-11-01

    The cholinergic neurotransmission within the human mesenteric lymphatic vessels has been poorly studied. Therefore, our aim is to analyse the cholinergic nerve fibres of lymphatic vessels using the traditional enzymatic techniques of staining, plus the biochemical modifications of acetylcholinesterase (AChE) activity. Specimens obtained from human mesenteric lymphatic vessels were subjected to the following experimental procedures: 1) drawing, cutting and staining of tissues; 2) staining of total nerve fibres; 3) enzymatic staining of cholinergic nerve fibres; 4) homogenisation of tissues; 5) biochemical amount of proteins; 6) biochemical amount of AChE activity; 6) quantitative analysis of images; 7) statistical analysis of data. The mesenteric lymphatic vessels show many AChE positive nerve fibres around their wall with an almost plexiform distribution. The incubation time was performed at 1 h (partial activity) and 6 h (total activity). Moreover, biochemical dosage of the same enzymatic activity confirms the results obtained with morphological methods. The homogenates of the studied tissues contain strong AChE activity. In our study, the lymphatic vessels appeared to contain few cholinergic nerve fibres. Therefore, it is expected that perivascular nerve stimulation stimulates cholinergic nerves innervating the mesenteric arteries to release the neurotransmitter AChE, which activates muscarinic or nicotinic receptors to modulate adrenergic neurotransmission. These results strongly suggest, that perivascular cholinergic nerves have little or no effect on the adrenergic nerve function in mesenteric arteries. The cholinergic nerves innervating mesenteric arteries do not mediate direct vascular responses.

  12. Mapping superficial lymphatic territories in the rabbit.

    Science.gov (United States)

    Soto-Miranda, Miguel A; Suami, Hiroo; Chang, David W

    2013-06-01

    Little is known about the anatomy of the lymphatic system in the rabbit with regard to relationships between the lymphatic vessel and lymph node. According to our previous studies in human cadavers and canines, the superficial lymphatic system could be divided into lymphatic territories. The aim of this study was to completely map the superficial lymphatic system in the rabbit. We used our microinjection technique and histological analysis for dissecting studies and recently developed indocyanine green (ICG) fluorescent lymphography for demonstrating dynamic lymph flow in living rabbits. Real-time ICG fluorescent lymphography was performed in two living New Zealand White rabbits, and direct dye microinjection of the lymphatic vessels was performed in eight dead rabbits. To assess the relationships between the vascular and lymphatic systems in rabbits, we performed radiocontrast injection into arteries in two dead rabbits prior to the lymphatic injection. The ICG fluorescent lymphography revealed eight lymphatic territories in the preauricular, submandibular, root of the lateral neck, axillary, lumbar, inguinal, root of the tail, and popliteal regions. We injected blue acrylic dye into every lymphatic vessel 0.1 mm in diameter or larger. We then dissected and chased the stained lymphatic vessels proximally until the vessels connected to the first tier lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The lymphatic system of the rabbit could be defined as eight lymphatic territories, each with its own lymphatic vessels and lymph node. Copyright © 2013 Wiley Periodicals, Inc.

  13. Effects of NM-3 on lymphatic vessel density and vascular endothelial growth factor of colon cancer in orthotopic implantation model of a severe combined immune deficiency mice

    Directory of Open Access Journals (Sweden)

    Jin-Shui Zhu

    2010-12-01

    Full Text Available The molecular mechanisms involved colon cancer tumorigenesis and development of colon cancer remain unclear. The aim of this study is to explore the inhibitive effects of NM-3 on lymphatic vessel density and vascular endothelial growth factor of micrometastatic lesion of orthotopic implantated colon cancer in the severe combined immune deficiency (SCID nude mice. Human colon cancer SW1116 cells were orthotopically implantated into the colon of the nude mice. Twenty-eight SCID nude mice were randomly divided into four groups (7 mice for each group after one week feeding and then the nude mice were treated with carboplatin and NM-3 via intraperitoneal injection twice a week for 8 weeks. The mice were sacrificed after 8 weeks and the vascular endothelial growth factor-C (VEGF-C, VEGF-D, VEGF-R-3 and lymphatic vessel density (LVD were analyzed using immunohistochemistry staining assay. LVD in NM-3 treated mice was significantly lower than that of control (normal saline treated mice. The expression of VEGF-C, VEGF-D, and VEGF-R-3 and the expression of mRNA of VEGF-C, VEGF-D, and VEGF-R-3 in NM-3 treated mice were significantly lower than that of control mice. The NM-3 inhibited the growth of colon cancer in the SCID mice of orthotopic implantatation model, and this effect may be related to the inhibitive effects of NM-3 on the lymphangiogenesis and vascular endothelial growth factor in colon cancer. NM-3 and carboplatin played a synergistic role in inhibiting lymphangiogenesis of human colon cancer in SCID nude mice and the further investigation of molecular mechanisms involved in colon cancer metastasis will provide an important evidence for understanding of lymphangiogenesis of human colon cancer.

  14. Lymphatic System in Cardiovascular Medicine.

    Science.gov (United States)

    Aspelund, Aleksanteri; Robciuc, Marius R; Karaman, Sinem; Makinen, Taija; Alitalo, Kari

    2016-02-05

    The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease. © 2016 American Heart Association, Inc.

  15. Co-expression of vascular and lymphatic endothelial cell markers on early endothelial cells present in aspirated coronary thrombi from patients with ST-elevation myocardial infarction.

    Science.gov (United States)

    Rakocevic, Jelena; Kojic, Snezana; Orlic, Dejan; Stankovic, Goran; Ostojic, Miodrag; Petrovic, Olga; Zaletel, Ivan; Puskas, Nela; Todorovic, Vera; Labudovic-Borovic, Milica

    2016-02-01

    Angiogenesis is the growth of both new vascular and lymphatic blood vessels from the existing vasculature. During this process, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) express specific markers, which help their discrimination and easier identification. Since the coronary thrombi material aspirated from patients with ST-elevation myocardial infarction (STEMI) proved as good angiogenesis model, we investigated the expression of CD34 and CD31 as BECs markers, and D2-40, LYVE-1 and VEGFR3 as LEC markers in this material. Aspirated thrombi were stained immunohistochemically for CD34, CD31, D2-40, LYVE-1 and VEGFR3. Organizational patterns of immunopositive cells were graded as single cells, clusters or microvessels. Double immunofluorescence for CD31, D2-40, LYVE-1 and VEGRF3 was done. Thrombi were also graded as fresh (5days old). Serial sections of aspirated thrombi showed concordant BEC and LEC markers immunopositivity. Double immunoflorescence proved co-expression of CD31 and LEC markers on the same cells. Cells expressing LEC markers organized in clusters and microvessels were mainly present in lytic and organized thrombi. Co-expression of BEC and LEC markers on the same non-tumorous cell during thrombus neovascularization indicates existing in vivo plasticity of endothelial cells under non-tumorous pathological conditions. It also points that CD34 and CD31 on one hand, and D2-40, LYVE-1 and VEGFR3 immunostaining on the other hand, cannot solely be a reliable indicators whether vessel is lymphatic or not. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Human platelet lysate is a feasible candidate to replace fetal calf serum as medium supplement for blood vascular and lymphatic endothelial cells.

    Science.gov (United States)

    Hofbauer, Pablo; Riedl, Sabrina; Witzeneder, Karin; Hildner, Florian; Wolbank, Susanne; Groeger, Marion; Gabriel, Christian; Redl, Heinz; Holnthoner, Wolfgang

    2014-09-01

    As angiogenic and lymphangiogenic key players, endothelial cells (ECs) are promising candidates for vascular regenerative therapies. To culture ECs in vitro, fetal calf serum (FCS) is most often used. However, some critical aspects of FCS usage, such as possible internalization of xenogeneic proteins and prions, must be considered. Therefore, the aim of this project was to determine if human platelet lysate (hPL) is a suitable alternative to FCS as medium supplement for the culture of blood vascular and lymphatic endothelial cells. The usability of hPL was tested by analysis of endothelial surface marker expression, metabolic activity and vasculogenic potential of outgrowth ECs (OECs), human umbilical vein ECs (HUVECs), and lymphatic ECs (LECs). Expression of EC markers CD31, VEGFR2, VE-cadherin and CD146 did not differ significantly between the EC types cultured in FCS or hPL. In addition, OECs, HUVECs and LECs formed tube-like structures on Matrigel when cultured in hPL and FCS. With the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assays, we found that the metabolic activity of OECs and LECs was slightly decreased when hPL was used. However, HUVECs and LECs did not show a significant decrease in metabolic activity, and HUVECs showed a slightly higher activity at low seeding densities. The use of hPL on different EC types did not reveal any substantial negative effects on EC behavior. Thus, hPL appears to be a favorable candidate to replace FCS as a medium supplement in the culture of ECs. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Mechanosensing in developing lymphatic vessels.

    Science.gov (United States)

    Planas-Paz, Lara; Lammert, Eckhard

    2014-01-01

    The lymphatic vasculature is responsible for fluid homeostasis, transport of immune cells, inflammatory molecules, and dietary lipids. It is composed of a network of lymphatic capillaries that drain into collecting lymphatic vessels and ultimately bring fluid back to the blood circulation. Lymphatic endothelial cells (LECs) that line lymphatic capillaries present loose overlapping intercellular junctions and anchoring filaments that support fluid drainage. When interstitial fluid accumulates within tissues, the extracellular matrix (ECM) swells and pulls the anchoring filaments. This results in opening of the LEC junctions and permits interstitial fluid uptake. The absorbed fluid is then transported within collecting lymphatic vessels, which exhibit intraluminal valves that prevent lymph backflow and smooth muscle cells that sequentially contract to propel lymph.Mechanotransduction involves translation of mechanical stimuli into biological responses. LECs have been shown to sense and respond to changes in ECM stiffness, fluid pressure-induced cell stretch, and fluid flow-induced shear stress. How these signals influence LEC function and lymphatic vessel growth can be investigated by using different mechanotransduction assays in vitro and to some extent in vivo.In this chapter, we will focus on the mechanical forces that regulate lymphatic vessel expansion during embryonic development and possibly secondary lymphedema. In mouse embryos, it has been recently shown that the amount of interstitial fluid determines the extent of lymphatic vessel expansion via a mechanosensory complex formed by β1 integrin and vascular endothelial growth factor receptor-3 (VEGFR3). This model might as well apply to secondary lymphedema.

  18. The effects of pneumoperitoneum and controlled ventilation on peritoneal lymphatic bacterial clearance: experimental results in rats

    Directory of Open Access Journals (Sweden)

    Armando Angelo Casaroli

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the effect of pneumoperitoneum, both alone and in combination with controlled ventilation, on peritoneal lymphatic bacterial clearance using a rat bacterial peritonitis model. METHOD: A total of 69 male Wistar rats were intraperitoneally inoculated with an Escherichia coli solution (109 colony-forming units (cfu/mL and divided into three groups of 23 animals each: A (control group, B (pneumoperitoneum under 5 mmHg of constant pressure, and C (endotracheal intubation, controlled ventilation, and pneumoperitoneum as in Group B. The animals were sacrificed after 30 min under these conditions, and blood, mediastinal ganglia, lungs, peritoneum, liver, and spleen cultures were performed. RESULTS: Statistical analyses comparing the number of cfu/sample in each of the cultures showed that no differences existed between the three groups. CONCLUSION: Based on our results, we concluded that pneumoperitoneum, either alone or in association with mechanical ventilation, did not modify the bacterial clearance through the diaphragmatic lymphatic system of the peritoneal cavity.

  19. Inflammation-induced lymphangiogenesis and lymphatic dysfunction

    Science.gov (United States)

    Liao, Shan; von der Weid, Pierre-Yves

    2014-01-01

    The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphatic contractile dysfunction occur in both vascular and nodal parts of the lymphatic system during inflammation, as well as other disease processes. This review provides a critical update on the role of the lymphatic system in disease process such as chronic inflammation and cancer and examines the changes in lymphatic functions the diseases cause and the influence these changes have on the progression of the diseases. PMID:24449090

  20. Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium

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    Rodriguez-Ruiz, María E., E-mail: mrruiz@unav.es [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Garasa, Saray; Rodriguez, Inmaculada [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Solorzano, Jose Luis; Barbes, Benigno [Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Yanguas, Alba [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Department of Biochemistry and Genetics, University of Navarra, Pamplona (Spain); Teijeira, Alvaro; Etxeberria, Iñaki [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Aristu, José Javier [Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Halin, Cornelia [Pharmaceutical Immunology, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich (Switzerland); Melero, Ignacio [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Radiation Oncology, University Clinic, University of Navarra, Pamplona (Spain); Rouzaut, Ana [Division of Immunology and Immunotherapy, Center for Applied Medical Research, University of Navarra, Pamplona (Spain); Department of Biochemistry and Genetics, University of Navarra, Pamplona (Spain)

    2017-02-01

    Purpose/Objectives: The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Materials/Methods: Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. Results: We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Conclusion: Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to

  1. Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium.

    Science.gov (United States)

    Rodriguez-Ruiz, María E; Garasa, Saray; Rodriguez, Inmaculada; Solorzano, Jose Luis; Barbes, Benigno; Yanguas, Alba; Teijeira, Alvaro; Etxeberria, Iñaki; Aristu, José Javier; Halin, Cornelia; Melero, Ignacio; Rouzaut, Ana

    2017-02-01

    The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to immunotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Acral hemosideric lymphatic malformation.

    Science.gov (United States)

    Wang, Lei; Gao, Tianwen; Wang, Gang

    2013-07-01

    Cutaneous lymphatic malformations represent a group of heterogeneous diseases caused by developmental defects of lymphatic system. The purpose of this study was to report the clinical, histopathological and immunohistochemical features of a distinctive lymphatic malformation. Twelve patients with similar clinical and histopathological features were included in this study. Immunohistochemical staining of CD31, D2-40, Prox1 and Wilms tumor 1 (WT-1) were performed on all lesions. All cases were either congenital lesions or developed during the first 2 years of life. All presented as red to brown papules or nodules on acral sites. Histopathologically, the lesions consisted of a dermal proliferation of flat or slit-like vessels lined with a single layer of endothelial cells. Hemosiderin or extravascular red blood cells were present in all cases. The constituent vessels expressed CD31, D2-40 and Prox1 and lacked expression of WT-1. On the basis of the clinical, histopathological and immunohistochemical findings, our cases represent a unique type of lymphatic malformation that we believe is distinct from previously reported vascular proliferations. We propose the name of acral hemosideric lymphatic malformation for this entity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Aberrant lymphatic endothelial progenitors in lymphatic malformation development.

    Directory of Open Access Journals (Sweden)

    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. Aberrant lymphatic endothelial progenitors in lymphatic malformation development.

    Science.gov (United States)

    Wu, June K; Kitajewski, Christopher; Reiley, Maia; Keung, Connie H; Monteagudo, Julie; Andrews, John P; Liou, Peter; Thirumoorthi, Arul; Wong, Alvin; Kandel, Jessica J; Shawber, Carrie J

    2015-01-01

    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.

  5. Vascular flora and macroscopic fauna on the Fernow Experimental Forest

    Science.gov (United States)

    Darlene M. Madarish; Jane L. Rodrigue; Mary Beth Adams

    2002-01-01

    This report is the first comprehensive inventory of the vascular flora and macroscopic fauna known to occur within the Fernow Experimental Forest in north-central West Virignia. The compendium is based on information obtained from previous surveys, current research, and the personal observations of USDA Forest Service personnel and independent scientists. More than 750...

  6. Abdominal lymphatic malformation: Spectrum of imaging findings

    Directory of Open Access Journals (Sweden)

    Anupam Lal

    2016-01-01

    Full Text Available Lymphatic malformations are congenital vascular malformations with lymphatic differentiation. Although the most common locations for lymphatic malformation are the neck and axilla, they can occur at several locations in the body including the abdomen. The abdominal location is rather rare and accounts for approximately 5% of all lymphatic malformation. Abdominal lymphatic malformation can arise from mesentery, omentum, gastrointestinal tract, and retroperitoneum. Clinical presentation includes an abdominal lump, vague abdominal discomfort, and secondary complications including intestinal obstruction, volvulus, ischemia, and bleeding. There is a broad spectrum of radiological manifestation. In the present review, we discuss the imaging appearance of abdominal lymphatic malformation. The diagnosis of lymphatic malformation in our series was based on the histopathological examination (in cases who underwent surgery and fine needle aspiration cytology.

  7. Abdominal lymphatic malformation: Spectrum of imaging findings.

    Science.gov (United States)

    Lal, Anupam; Gupta, Pankaj; Singhal, Manphool; Sinha, Saroj K; Lal, Sadhana; Rana, Surinder; Khandelwal, Niranjan

    2016-01-01

    Lymphatic malformations are congenital vascular malformations with lymphatic differentiation. Although the most common locations for lymphatic malformation are the neck and axilla, they can occur at several locations in the body including the abdomen. The abdominal location is rather rare and accounts for approximately 5% of all lymphatic malformation. Abdominal lymphatic malformation can arise from mesentery, omentum, gastrointestinal tract, and retroperitoneum. Clinical presentation includes an abdominal lump, vague abdominal discomfort, and secondary complications including intestinal obstruction, volvulus, ischemia, and bleeding. There is a broad spectrum of radiological manifestation. In the present review, we discuss the imaging appearance of abdominal lymphatic malformation. The diagnosis of lymphatic malformation in our series was based on the histopathological examination (in cases who underwent surgery) and fine needle aspiration cytology.

  8. Lymphatic Filariasis

    Science.gov (United States)

    ... FAQs) Vectors of Lymphatic Filariasis Epidemiology & Risk Factors Biology ... microscopic, thread-like worms. The adult worms only live in the human lymph system. The lymph system maintains the body's fluid balance ...

  9. Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm's Canal Reporter Rat.

    Science.gov (United States)

    Jung, Eunson; Gardner, Daniel; Choi, Dongwon; Park, Eunkyung; Jin Seong, Young; Yang, Sara; Castorena-Gonzalez, Jorge; Louveau, Antoine; Zhou, Zhao; Lee, Gene K; Perrault, David P; Lee, Sunju; Johnson, Maxwell; Daghlian, George; Lee, Maria; Jin Hong, Yeo; Kato, Yukinari; Kipnis, Jonathan; Davis, Michael J; Wong, Alex K; Hong, Young-Kwon

    2017-07-17

    The lymphatic system plays a key role in tissue fluid homeostasis, immune cell trafficking, and fat absorption. We previously reported a bacterial artificial chromosome (BAC)-based lymphatic reporter mouse, where EGFP is expressed under the regulation of the Prox1 promoter. This reporter line has been widely used to conveniently visualize lymphatic vessels and other Prox1-expressing tissues such as Schlemm's canal. However, mice have a number of experimental limitations due to small body size. By comparison, laboratory rats are larger in size and more closely model the metabolic, physiological, and surgical aspects of humans. Here, we report development of a novel lymphatic reporter rat using the mouse Prox1-EGFP BAC. Despite the species mismatch, the mouse Prox1-EGFP BAC enabled a reliable expression of EGFP in Prox1-expressing cells of the transgenic rats and allowed a convenient visualization of all lymphatic vessels, including those in the central nervous system, and Schlemm's canal. To demonstrate the utility of this new reporter rat, we studied the contractile properties and valvular functions of mesenteric lymphatics, developed a surgical model for vascularized lymph node transplantation, and confirmed Prox1 expression in venous valves. Together, Prox1-EGFP rat model will contribute to the advancement of lymphatic research as a valuable experimental resource.

  10. Temporal and Spatial Regulation of Epsin Abundance and VEGFR3 Signaling are Required for Lymphatic Valve Formation and Function

    OpenAIRE

    Liu, Xiaolei; Pasula, Satish; Song, Hoogeun; Tessneer, Kandice L.; Dong, Yunzhou; Hahn, Scott; Yago, Tadayuki; Brophy, Megan; Chang, Baojun; Cai, Xiaofeng; Wu, Hao; McManus, John; Ichise, Hirotake; Georgescu, Constantin; Wren, Jonathan D

    2014-01-01

    Lymphatic valves prevent the backflow of the lymph fluid and ensure proper lymphatic drainage throughout the body. Local accumulation of lymphatic fluid in tissues, a condition called lymphedema, is common in individuals with malformed lymphatic valves. The vascular endothelial growth factor receptor 3 (VEGFR3) is required for the development of lymphatic vascular system. The abundance of VEGFR3 in collecting lymphatic trunks is high before valve formation and, except at valve regions, decrea...

  11. Expression of vascular endothelial growth factors VEGF- C and D, VEGFR-3, and comparison of lymphatic vessels density labeled with D2-40 antibodies as a prognostic factors in vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer.

    Science.gov (United States)

    Jach, Robert; Dyduch, Grzegorz; Radon-Pokracka, Malgorzata; Przybylska, Paulina; Mika, Marcin; Dulinska-Litewka, Joanna; Zajac, Krzysztof; Huras, Hubert; Streb, Joanna; Stangel-Wojcikiewicz, Klaudia; Dziadek, Olivia; Galarowicz, Bartlomiej

    2011-01-01

    The aim of this study was to compare the immunohistochemical expression of vascular endothelial growth factors VEGF-C and D, as well as the expression of VEGFR-3 in VIN and vulvar invasive cancer and to compare the density of lymphatic marker D2-40 antibody in both groups, and to compare them with different clinicopathologic features. The study was performed using tissue material and clinical data from 100 women diagnosed with VIN and 100 women diagnosed with invasive vulvar cancer. No significant differences were found in the expression of VEGF-C and -D or VEGFR-3 between those patients with VIN and those with invasive vulvar cancers. Weak expression of VEGF-C was confirmed only in two cases of the analyzed series; in all cases, expression of VEGF-D and VEGFR-3 was observed. The strongest expression of VEGF-D and VEGFR-3 was observed in the group of invasive cancers. The highest density of lymphatic vessels per 2 mm was observed in VIN. In the cancer group, small lymphatic vessels with a narrow oval lumen were observed. Moreover, in two cases of vulvar cancer, the presence of intratumoral lymphatic vessels was observed. These results suggest that lymphangiogenesis begins at the preinvasive stage of vulvar carcinogenesis and suggests the important role of VEGF-C, VEGF-D, VEGFR-3 and LV (D2-40) as prognostic factors in the process of carcinogenesis in the vulvar area.

  12. Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis

    Directory of Open Access Journals (Sweden)

    Rocha Gislene FS

    2008-02-01

    Full Text Available Abstract Background Immunohistochemical studies of lymphatic vessels have been limited by a lack of specific markers. Recently, the novel D2-40 antibody, which selectively marks endothelium of lymphatic vessels, was released. The aim of our study is to compare lymphatic and blood vessel invasion detected by hematoxylin and eosin (H&E versus that detected by immunohistochemistry, relating them with morphologic and molecular prognostic factors. Methods We selected 123 cases of invasive mammary carcinomas stratified into three subgroups according to axillary lymph node status: macrometastases, micrometastases, and lymph node negative. Lymphatic (LVI and blood (BVI vessel invasion were evaluated by H&E and immunohistochemistry using the D2-40 and CD31 antibodies, and related to histologic tumor type and grade, estrogen and progesterone receptors, E-cadherin, Ki67, p53, and Her2/neu expression. Results LVI was detected in H&E-stained sections in 17/123 cases (13.8%, and in D2-40 sections in 35/123 cases (28.5% (Kappa = 0.433. BVI was detected in H&E-stained sections in 5/123 cases (4.1%, and in CD31 stained sections in 19/123 cases (15.4% (Kappa = 0.198. LVI is positively related to higher histologic grade (p = 0.013, higher Ki67 expression (p = 0.00013, and to the presence of macrometastases (p = 0.002, and inversely related to estrogen (p = 0.0016 and progesterone (p = 0.00017 receptors expression. Conclusion D2-40 is a reliable marker of lymphatic vessels and is a useful tool for lymphatic emboli identification in immunostained sections of breast carcinomas with higher identification rates than H&E. Lymphatic vessel invasion was related to other features (high combined histologic grade, high Ki67 score, negative hormone receptors expression associated with worse prognosis, probable reflecting a potential for lymphatic metastatic spread and aggressive behavior.

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

    Directory of Open Access Journals (Sweden)

    Kelly L Hall

    Full Text Available 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.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.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 fundamental features of endogenous M-LECPs. Unlike native LECPs, this model

  14. 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 ... December 8, 2017 11.08.2017 The Lymphatic Education & Research Network… Read More > ASRM LE&RN Combined ...

  15. Lymphatic Anomalies Registry

    Science.gov (United States)

    2016-07-26

    Lymphatic Malformation; Generalized Lymphatic Anomaly (GLA); Central Conducting Lymphatic Anomaly; CLOVES Syndrome; Gorham-Stout Disease ("Disappearing Bone Disease"); Blue Rubber Bleb Nevus Syndrome; Kaposiform Lymphangiomatosis; Kaposiform Hemangioendothelioma/Tufted Angioma; Klippel-Trenaunay Syndrome; Lymphangiomatosis

  16. The expression of vascular endothelial growth factor-C correlates with lymphatic microvessel density and lymph node metastasis in prostate carcinoma: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Gyftopoulos Kostis

    2014-01-01

    Conclusions: Our results indicate that increased peritumoral (but not intratumoral LVD in the tumor specimen is associated with lymph node metastasis. Increased expression of VEGF-C is associated with higher LVD (in both intratumoral and peritumoral compartments and with positive lymph node status, indicating a possible dual role in both lymphangiogenesis and lymphatic vessel invasion.

  17. Dendritic Cell Interactions with Lymphatic Endothelium

    Science.gov (United States)

    Russo, Erica; Nitschké, Maximilian

    2013-01-01

    Abstract Afferent lymphatic vessels fulfill essential immune functions by transporting leukocytes and lymph-borne antigen to draining lymph nodes (dLNs). An important cell type migrating through lymphatic vessels are dendritic cells (DCs). DCs reside in peripheral tissues like the skin, where they take up antigen and transport it via the lymphatic vascular network to dLNs for subsequent presentation to T cells. As such, DCs play a key role in the induction of adaptive immune responses during infection and vaccination, but also for the maintenance of tolerance. Although the migratory pattern of DCs has been known for long time, interactions between DCs and lymphatic vessels are only now starting to be unraveled at the cellular level. In particular, new tools for visualizing lymphatic vessels in combination with time-lapse microscopy have recently generated valuable insights into the process of DC migration to dLNs. In this review we summarize and discuss current approaches for visualizing DCs and lymphatic vessels in tissues for imaging applications. Furthermore, we review the current state of knowledge about DC migration towards, into and within lymphatic vessels, particularly focusing on the cellular interactions that take place between DCs and the lymphatic endothelium. PMID:24044757

  18. 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.

  19. Progression of Inflammatory Bowel Disease to Cancer: Is the Patient Better Off without Lymphatic Vessels or Nodes (or Angiopoietin 2)?

    Science.gov (United States)

    2013-12-01

    various theories of progression have remained elusive. We proposed that a reduced number of functioning lymphatic vessels and impaired lymph drainage ...having a reduced number of functioning lymphatic vessels and impaired lymph drainage ( lymphatic vascular insufficiency) in the colon actually protects... Lymphatic Vessels or Nodes (or Angiopoietin 2)? PRINCIPAL INVESTIGATOR: Marlys H. Witte, MD CONTRACTING ORGANIZATION: University of Arizona, Tucson

  20. GIANT CYSTIC CERVICAL LYMPHATIC MALFORMATION

    OpenAIRE

    N. Danila; D. Andronic; Luca Beatrice; Popa, E.; A. Nistor; D. Ferariu

    2006-01-01

    The lymphatic malformations of the neck (LMN) are rare diseases, which increase progressively until very large size. The clinical symptoms are pressure signs, due to the compression to the respiratory, digestive and vascular structures of the neck. The authors are presenting the clinical case of a 77 yo male patient with history of simple diffuse goiter. During the evolution, the cervical mass increases progressively its sizes, but in the last 2-3 months before the admission in our clinic t...

  1. Experimental autologous substitute vascular graft for transplantation surgery

    NARCIS (Netherlands)

    Kobori, L; Dallos, G; Gouw, ASH; Nemeth, T; Nemes, B; Fehervari, I; Tegzess, Adam; Slooff, MJH; Perner, F; De Jong, KP

    2000-01-01

    Vascular complications in fiver transplantation are a major cause of graft failure and mortality. The aim of the study was to create autologous vascular graft without risk of rejection. Posterior rectus fascia sheath lined with peritoneum was used for iliac artery replacement in seven mongrel dogs.

  2. Calcium Dobesilate Prevents Neurodegeneration and Vascular Leakage in Experimental Diabetes.

    Science.gov (United States)

    Solà-Adell, Cristina; Bogdanov, Patricia; Hernández, Cristina; Sampedro, Joel; Valeri, Marta; Garcia-Ramirez, Marta; Pasquali, Christian; Simó, Rafael

    2017-09-01

    The mechanisms involved in the reported beneficial effects of Calcium dobesilate monohydrate (CaD) for the treatment of diabetic retinopathy (DR) remain to be elucidated. The main aim of the present study is to examine whether CaD prevents early events in the pathogenesis of DR such as neurodegeneration and vascular leakage. In addition, putative mediators of both neurodegeneration (glutamate/GLAST, ET-1/ETB receptor) and early microvascular impairment (ET-1/ETA receptor, oxidative stress, VEGF, and the PKC-delta-p38 MAPK pathway) have been examined. Diabetic (db/db) mice were randomly assigned to daily oral treatment with CaD (200 mg/Kg/day) (n = 12) or vehicle (n = 12) for 14 days. In addition, 12 non-diabetic (db/+) mice matched by age were used as the control group. Functional abnormalities were assessed by electroretinography. Neurodegeneration and microvascular abnormalities were evaluated by immunohistochemistry and Western blot. Glutamate was determined by HPLC. CaD significantly decreased glial activation and apoptosis and produced a significant improvement in the electroretinogram parameters. Mechanistically, CaD prevented the diabetes-induced up-regulation of ET-1 and its cognate receptors (ETA-R and ETB-R), which are involved in microvascular impairment and neurodegeneration, respectively. In addition, treatment with CaD downregulated GLAST, the main glutamate transporter, and accordingly prevented the increase in glutamate. Finally, CaD prevented oxidative stress, and the upregulation of VEGF and PKC delta-p38 MAPK pathway induced by diabetes, thus resulting in a significant reduction in vascular leakage. Our findings demonstrate for the first time that CaD exerts neuroprotection in an experimental model of DR. In addition, we provide first evidence that CaD prevents the overexpression of ET-1 and its receptors in the diabetic retina. These beneficial effects on the neurovascular unit could pave the way for clinical trials addressed to confirm the

  3. Blood flow reprograms lymphatic vessels to blood vessels.

    Science.gov (United States)

    Chen, Chiu-Yu; Bertozzi, Cara; Zou, Zhiying; Yuan, Lijun; Lee, John S; Lu, MinMin; Stachelek, Stan J; Srinivasan, Sathish; Guo, Lili; Vicente, Andres; Vincente, Andres; Mericko, Patricia; Levy, Robert J; Makinen, Taija; Oliver, Guillermo; Kahn, Mark L

    2012-06-01

    Human vascular malformations cause disease as a result of changes in blood flow and vascular hemodynamic forces. Although the genetic mutations that underlie the formation of many human vascular malformations are known, the extent to which abnormal blood flow can subsequently influence the vascular genetic program and natural history is not. Loss of the SH2 domain-containing leukocyte protein of 76 kDa (SLP76) resulted in a vascular malformation that directed blood flow through mesenteric lymphatic vessels after birth in mice. Mesenteric vessels in the position of the congenital lymphatic in mature Slp76-null mice lacked lymphatic identity and expressed a marker of blood vessel identity. Genetic lineage tracing demonstrated that this change in vessel identity was the result of lymphatic endothelial cell reprogramming rather than replacement by blood endothelial cells. Exposure of lymphatic vessels to blood in the absence of significant flow did not alter vessel identity in vivo, but lymphatic endothelial cells exposed to similar levels of shear stress ex vivo rapidly lost expression of PROX1, a lymphatic fate-specifying transcription factor. These findings reveal that blood flow can convert lymphatic vessels to blood vessels, demonstrating that hemodynamic forces may reprogram endothelial and vessel identity in cardiovascular diseases associated with abnormal flow.

  4. 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 been fully ... Material and methods: We studied the regeneration of lymphatic vessels in the rat skin incisional wounds (sutured ... lymphatic vessels sprouting in experimental rabbit ear wounds.9The ...

  5. Ginsenoside Rg1 enhances lymphatic transport of intrapulmonary silica via VEGF-C/VEGFR-3 signaling in silicotic rats.

    Science.gov (United States)

    Yu, Jie; Mao, Lijun; Guan, Li; Zhang, Yanlin; Zhao, Jinyuan

    2016-03-25

    Ginsenoside Rg1, extracted mainly from Panax ginseng, has been shown to exert strong pro-angiogenic activities in vivo. But it is unclear whether ginsenoside Rg1 could promote lung lymphangiogenesis to improve lymphatic transport of intrapulmonary silica in silicotic rats. Here we investigated the effect of ginsenoside Rg1 on lymphatic transport of silica during experimental silicosis, and found that ginsenoside Rg1 treatment significantly raised the silicon content in tracheobronchial lymph nodes and serum to reduce the silicon level in lung interstitium, meanwhile increased pulmonary lymphatic vessel density by enhancing the protein and mRNA expressions of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3). The stimulative effect of ginsenoside Rg1 on lymphatic transport of silica was actively correlated with its pro-lymphangiogenic identity. And VEGFR-3 inhibitor SAR131675 blocked these above effects of ginsenoside Rg1. These findings suggest that ginsenoside Rg1 exhibits good protective effect against lung burden of silica during experimental silicosis through improving lymphatic transport of intrapulmonary silica, which is potentially associated with the activation of VEGF-C/VEGFR-3 signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Program requirements for fellowship education in venous and lymphatic medicine.

    Science.gov (United States)

    Comerota, Anthony J; Min, Robert J; Rathbun, Suman W; Khilnani, Neil; Rooke, Thom; Wakefield, Thomas W; Carman, Teresa L; Lurie, Fedor; Vedantham, Suresh; Zimmet, Steven E

    2017-08-01

    Background In every field of medicine, comprehensive education should be delivered at the graduate level. Currently, no single specialty routinely provides a standardized comprehensive curriculum in venous and lymphatic disease. Method The American Board of Venous & Lymphatic Medicine formed a task force, made up of experts from the specialties of dermatology, family practice, interventional radiology, interventional cardiology, phlebology, vascular medicine, and vascular surgery, to develop a consensus document describing the program requirements for fellowship medical education in venous and lymphatic medicine. Result The Program Requirements for Fellowship Education in Venous and Lymphatic Medicine identify the knowledge and skills that physicians must master through the course of fellowship training in venous and lymphatic medicine. They also specify the requirements for venous and lymphatic training programs. The document is based on the Core Content for Training in Venous and Lymphatic Medicine and follows the ACGME format that all subspecialties in the United States use to specify the requirements for training program accreditation. The American Board of Venous & Lymphatic Medicine Board of Directors approved this document in May 2016. Conclusion The pathway to a vein practice is diverse, and there is no standardized format available for physician education and training. The Program Requirements for Fellowship Education in Venous and Lymphatic Medicine establishes educational standards for teaching programs in venous and lymphatic medicine and will facilitate graduation of physicians who have had comprehensive training in the field.

  7. α-Solanine reverses pulmonary vascular remodeling and vascular angiogenesis in experimental pulmonary artery hypertension.

    Science.gov (United States)

    Nie, Xiaowei; Dai, Youai; Tan, Jianxin; Chen, Yuan; Qin, Guowei; Mao, Wenjun; Zou, Jian; Chang, Yanhua; Wang, Qian; Chen, Jingyu

    2017-12-01

    Similar to cancer, pulmonary arterial hypertension (PAH) is characterized by vascular remodeling, which leads to obliteration of the small pulmonary arteriole, with marked proliferation of pulmonary artery smooth muscle cells (PASMC) and/or endothelial cells dysfunction. Aberrant expression of tumor suppressor genes is closely associated with susceptibility to PAH. We hypothesized that α-solanine, a glycoalkaloid found in members of the nightshade family known to have antitumor activity in different cancers, reverses experimental PAH by activating the tumor suppressor-axis inhibition protein 2 (AXIN2). We investigated the effects of α-solanine on PASMC proliferation and apoptosis by using 5-ethynyl-2'-deoxyuridine proliferation assay, proliferating cell nuclear antigen and Ki67 staining, TUNEL and Anexine V assays. Scratch wound healing and tube formation assays were also used to study migration of endothelial cells. In vitro, we demonstrated, using cultured human PASMC from PAH patients, that α-solanine reversed dysfunctional AXIN2, β-catenin and bone morphogenetic protein receptor type-2 signaling, whereas restored [Ca]i, IL-6 and IL-8, contributing to the decrease of PAH-PASMC proliferation and resistance to apoptosis. Meanwhile, α-solanine inhibits proliferation, migration and tube formation of PAH-pulmonary artery endothelial cells by inhibiting Akt/GSK-3α activation. In vivo, α-solanine administration decreases distal pulmonary arteries remodeling, mean pulmonary arteries pressure and right ventricular hypertrophy in both monocrotaline-induced and Sugen/hypoxia-induced PAH in mice. This study demonstrates that AXIN2/β-catenin axis and Akt pathway can be therapeutically targeted by α-solanine in PAH. α-Solanine could be used as a new therapeutic strategy for the treatment of PAH.

  8. Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation

    NARCIS (Netherlands)

    Karpanen, Terhi; Wirzenius, Maria; Mäkinen, Taija; Veikkola, Tanja; Haisma, Hidde J; Achen, Marc G; Stacker, Steven A; Pytowski, Bronislaw; Ylä-Herttuala, Seppo; Alitalo, Kari

    Lymphatic vessel plasticity and stability are of considerable importance when attempting to treat diseases associated with the lymphatic vasculature. Development of lymphatic vessels during embryogenesis is dependent on vascular endothelial growth factor (VEGF)-C but not VEGF-D. Using a recombinant

  9. Spleen and Lymphatic System

    Science.gov (United States)

    ... Stones Brain and Nervous System Spleen and Lymphatic System KidsHealth > For Teens > Spleen and Lymphatic System Print A A A What's in this article? ... El bazo y el sistema linfático The lymphatic system is an extensive drainage network that helps keep ...

  10. Rare lymphatic malformation in an extreme premature infant: answer

    National Research Council Canada - National Science Library

    Veronica Mugarab Samedi; Adel Elsharkawy

    2017-01-01

    .... No other anomalies were detected, genetic screening for infant was normal. Despite of size of lymphatic malformation at birth, it was an isolated finding with minimal vascularity, thus the prognosis for self-resolution was very good...

  11. Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography.

    Directory of Open Access Journals (Sweden)

    Sang Kyum Kim

    Full Text Available Human hepatocellular carcinoma (HCC has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability.In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin-Cre/WW45fl/fl, and H-ras12V genetically modified mouse models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography.H-ras12V transgenic mice (a HCC and hepatic adenoma model developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion, indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion.Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous closely simulated typical characteristics of human HCC vascular imaging.

  12. Lymphatic anatomy and biomechanics.

    Science.gov (United States)

    Negrini, Daniela; Moriondo, Andrea

    2011-06-15

    Lymph formation is driven by hydraulic pressure gradients developing between the interstitial tissue and the lumen of initial lymphatics. While in vessels equipped with lymphatic smooth muscle cells these gradients are determined by well-synchronized spontaneous contractions of vessel segments, initial lymphatics devoid of smooth muscles rely on tissue motion to form lymph and propel it along the network. Lymphatics supplying highly moving tissues, such as skeletal muscle, diaphragm or thoracic tissues, undergo cyclic compression and expansion of their lumen imposed by local stresses arising in the tissue as a consequence of cardiac and respiratory activities. Active muscle contraction and not passive tissue displacement is required to support an efficient lymphatic drainage, as suggested by the fact that the respiratory activity promotes lymph formation during spontaneous, but not mechanical ventilation. The mechanical properties of the lymphatic wall and of the surrounding tissue also play an important role in lymphatic function. Modelling of stress distribution in the lymphatic wall suggests that compliant vessels behave as reservoirs accommodating absorbed interstitial fluid, while lymphatics with stiffer walls, taking advantage of a more efficient transmission of tissue stresses to the lymphatic lumen, propel fluid through the lumen of the lymphatic circuit.

  13. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  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. Multiple adjustable vascular clamp prototype: feasibility study on an experimental model of end-to-side microsurgical vascular anastomosis.

    Science.gov (United States)

    Pereira, A; Ichihara, S; Collon, S; Bodin, F; Gay, A; Facca, S; Liverneaux, P

    2014-12-01

    The aim of this study was to establish the feasibility of microsurgical end-to-side vascular anastomosis with a multiclamp adjustable vascular clamp prototype in an inert experimental model. Our method consisted of performing an end-to-side microsurgical anastomosis with 10/0 suture on a 2-mm diameter segment. In group 1, the end-to-side segment was held in place by a double clamp and a single end clamp. In group 2, the segment was held in place with a single multiclamp adjustable clamp. The average time for performing the anastomosis was shorter in group 2. The average number of sutures was the same in both groups. No leak was found and permeability was always positive in both groups. Our results show that performing end-to-side anastomosis with a multiclamp adjustable vascular clamp is feasible in an inert experimental model. Feasibility in a live animal model has to be demonstrated before clinical use. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Neuroprotective effect of selective DPP-4 inhibitor in experimental vascular dementia.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2015-12-01

    Vascular risk factors are associated with a higher incidence of dementia. Diabetes mellitus is considered as a main risk factor for Alzheimer's disease and vascular dementia. Both forms of dementia are posing greater risk to the world population and are increasing at a faster rate. In the past we have reported the induction of vascular dementia by experimental diabetes. This study investigates the role of vildagliptin, a dipeptidyl peptidase-4 inhibitor in the pharmacological interdiction of pancreatectomy diabetes induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. Pancreatectomy diabetes rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with increase in brain inflammation, oxidative stress and calcium. Administration of vildagliptin has significantly attenuated pancreatectomy induced impairment of learning, memory, endothelial function, blood brain barrier permeability and biochemical parameters. It may be concluded that vildagliptin, a dipeptidyl peptidase-4 inhibitor may be considered as potential pharmacological agents for the management of pancreatectomy induced endothelial dysfunction and subsequent vascular dementia. The selective modulators of dipeptidyl peptidase-4 may further be explored for their possible benefits in vascular dementia. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Oral Carnosine Supplementation Prevents Vascular Damage in Experimental Diabetic Retinopathy

    NARCIS (Netherlands)

    Pfister, Frederick; Riedl, Eva; Wang, Qian; vom Hagen, Franziska; Deinzer, Martina; Harmsen, Martin Conrad; Molema, Grietje; Yard, Benito; Feng, Yuxi; Hammes, Hans-Peter

    2011-01-01

    Backgrounds/Aims: Pericyte loss, vasoregression and neuroglial activation are characteristic changes in incipient diabetic retinopathy. In this study, the effect of the antioxidant and antiglycating dipeptide carnosine was studied on the development of experimental diabetic retinopathy.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Bleomycin sclerotherapy for lymphatic malformation after unsuccessful surgical excision: case report.

    Science.gov (United States)

    Vlahovic, A; Gazikalovic, A; Adjic, O

    2015-10-01

    Lymphatic malformations (LMs) are benign cystic masses resulting from the abnormal development of lymphatic channels. Lymphatic malformations occur primarily in the head and neck region. Surgical excision of lymphatic malformation is followed by high rate of recurrence and a high risk of complications. Bleomycin is an established antineoplastic drug. It can be used as a sclerosing agent in vascular anomalies. We present a child who was unsuccessfully treated with four surgical resections, with peripheral palsy of facial nerve as complication. The lymphatic malformation was successfully treated in our institution with intralesional administration of bleomycin.

  20. Cardiac Lymphatic Vessels, Transport, and Healing of the Infarcted Heart

    Directory of Open Access Journals (Sweden)

    Li-Hao Huang, PhD

    2017-08-01

    Full Text Available The lymphatic vasculature plays a key role in regulating tissue fluid homeostasis, lipid transport, and immune surveillance throughout the body. Although it has been appreciated that the heart relies on lymphatic vessels to maintain fluid balance and that such balance must be tightly maintained to allow for normal cardiac output, it has only recently come to light that the lymphatic vasculature may serve as a therapeutic target with which to promote optimal healing following myocardial ischemia and infarction. This article reviews the subject of cardiac lymphatic vessels and highlights studies that imply targeting of lymphatic vessel development or transport using vascular endothelial growth factor-C therapy may serve as a promising avenue for future clinical application in the context of ischemic injury.

  1. Experimental examinations with a new percutaneously insertable, expandable vascular endoprosthesis

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, E.P.; Berg, G.; Weber, H.; Bohl, M.; Dietrich, B.

    1987-12-01

    Restenosis and occlusion are the most common reasons why transluminal balloon angioplasty may fail to provide long-term benefit. To prevent restonosis and occlusion of diseased arteries after angioplasty an arterial endoprosthesis has been developed which is positioned to the balloon of an angioplasty catheter and which consists of a stainless steel pliable and elastic tube. With the inflation of the balloon the endoprosthesis will dilate and give the arterial wall a new mechanical support. This new device has been implanted in 12 experimental dogs in arteries of different size and lumen. The longest patency rate of nine months was observed with the completely developed method.

  2. Obesity-induced lymphatic dysfunction is reversible with weight loss.

    Science.gov (United States)

    Nitti, Matthew D; Hespe, Geoffrey E; Kataru, Raghu P; García Nores, Gabriela D; Savetsky, Ira L; Torrisi, Jeremy S; Gardenier, Jason C; Dannenberg, Andrew J; Mehrara, Babak J

    2016-12-01

    Obesity induces lymphatic leakiness, decreases initial lymphatic vessel density, impairs collecting vessel pumping and decreases transport of macromolecules. Obesity results in perilymphatic inducible nitric oxide synthase (iNOS) expression and accumulation of T cells and macrophages. Deleterious effects of obesity on the lymphatic system correlate with weight gain. Weight loss restores lymphatic function in obese animals and decreases perilymphatic iNOS and inflammatory cell accumulation. Although clinical and experimental studies have shown that obesity results in lymphatic dysfunction, it remains unknown whether these changes are permanent or reversible with weight loss. In the current study, we used a mouse model of diet-induced obesity to identify putative cellular mechanisms of obesity-induced lymphatic dysfunction, determine whether there is a correlation between these deleterious effects and increasing weight gain, and finally examine whether lymphatic dysfunction is reversible with diet-induced weight loss. We report that obesity is negatively correlated with cutaneous lymphatic collecting vessel pumping rate (r = -0.9812, P weight gain and accumulation of perilymphatic inflammatory cells (r = 0.9872, P Weight loss resulting from conversion to a normal chow diet for 8 weeks resulted in more than a 25% decrease in body weight and normalized cutaneous lymphatic collecting vessel pumping rate, lymphatic vessel density, lymphatic leakiness, and lymphatic macromolecule clearance (all P weight loss markedly decreased perilymphatic inflammation and iNOS expression. Taken together, our findings show that obesity is linearly correlated with lymphatic dysfunction, perilymphatic inflammation and iNOS expression, and that weight loss via dietary modification effectively reverses these deleterious effects. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  3. A Model for Interstitial Drainage Through a Sliding Lymphatic Valve.

    Science.gov (United States)

    Heppell, Charles; Roose, Tiina; Richardson, Giles

    2015-06-01

    This study investigates fluid flow and elastic deformation in tissues that are drained by the primary lymphatic system. A model is formulated based on the Rossi hypothesis that states that the primary lymphatic valves, which are formed by overlapping endothelial cells around the circumferential lining of lymphatic capillaries, open in response to swelling of the surrounding tissue. Tissue deformation and interstitial fluid flow through the tissue are treated using the Biot equations of poroelasticity and, the fluid flux (into the interstitium) across the walls of the blood capillaries, is assumed to be linearly related to the pressure difference across the walls via a constant of proportionality (the vascular permeability). The resulting model is solved in a periodic domain containing one blood capillary and one lymphatic capillary starting from a configuration in which the tissue is undeformed. On imposition of a constant pressure difference between blood and lymphatic capillaries, the solutions are found to settle to a steady state. Given that the magnitude of pressure fluctuations in the lymphatic system is much smaller than this pressure difference between blood and lymph, it is postulated that the resulting steady-state solution gives a good representation of the state of the tissue under physiological conditions. The effects of changes to the Young's modulus of the tissue, the blood-lymphatic pressure difference, vascular permeability and valve dimensions on the steady state are investigated and discussed in terms of their effects on oedema in the context of age- and pregnancy-related changes to the body.

  4. Lymphatic vessels: new targets for the treatment of inflammatory diseases.

    Science.gov (United States)

    Dieterich, Lothar C; Seidel, Catharina D; Detmar, Michael

    2014-04-01

    The lymphatic system plays an important role in the physiological control of the tissue fluid balance and in the initiation of immune responses. Recent studies have shown that lymphangiogenesis, the growth of new lymphatic vessels and/or the expansion of existing lymphatic vessels, is a characteristic feature of acute inflammatory reactions and of chronic inflammatory diseases. In these conditions, lymphatic vessel expansion occurs at the tissue level but also within the draining lymph nodes. Surprisingly, activation of lymphatic vessel function by delivery of vascular endothelial growth factor-C exerts anti-inflammatory effects in several models of cutaneous and joint inflammation. These effects are likely mediated by enhanced drainage of extravasated fluid and inflammatory cells, but also by lymphatic vessel-mediated modulation of immune responses. Although some of the underlying mechanisms are just beginning to be identified, lymphatic vessels have emerged as important targets for the development of new therapeutic strategies to treat inflammatory conditions. In this context, it is of great interest that some of the currently used anti-inflammatory drugs also potently activate lymphatic vessels.

  5. Mechanobiology of lymphatic contractions.

    Science.gov (United States)

    Munn, Lance L

    2015-02-01

    The lymphatic system is responsible for controlling tissue fluid pressure by facilitating flow of lymph (i.e. the plasma and cells that enter the lymphatic system). Because lymph contains cells of the immune system, its transport is not only important for fluid homeostasis, but also immune function. Lymph drainage can occur via passive flow or active pumping, and much research has identified the key biochemical and mechanical factors that affect output. Although many studies and reviews have addressed how tissue properties and fluid mechanics (i.e. pressure gradients) affect lymph transport [1-3] there is less known about lymphatic mechanobiology. As opposed to passive mechanical properties, mechanobiology describes the active coupling of mechanical signals and biochemical pathways. Lymphatic vasomotion is the result of a fascinating system affected by mechanical forces exerted by the flowing lymph, including pressure-induced vessel stretch and flow-induced shear stresses. These forces can trigger or modulate biochemical pathways important for controlling the lymphatic contractions. Here, I review the current understanding of lymphatic vessel function, focusing on vessel mechanobiology, and summarize the prospects for a comprehensive understanding that integrates the mechanical and biomechanical control mechanisms in the lymphatic system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells

    Science.gov (United States)

    Jung, Wonhyuek; Seong, Young Jin; Park, Eunkyung; Bramos, Athanasios; Kim, Kyu Eui; Lee, Sunju; Daghlian, George; Seo, Jung In; Choi, Inho; Choi, In-Seon; Koh, Chester J.; Kobielak, Agnieszka; Ying, Qi-Long; Johnson, Maxwell; Gardner, Daniel; Wong, Alex K.; Choi, Dongwon; Hong, Young-Kwon

    2016-01-01

    Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research. PMID:27280889

  7. Effects of fatty acid synthase inhibitors on lymphatic vessels: an in vitro and in vivo study in a melanoma model.

    Science.gov (United States)

    Bastos, Débora C; Paupert, Jenny; Maillard, Catherine; Seguin, Fabiana; Carvalho, Marco A; Agostini, Michelle; Coletta, Ricardo D; Noël, Agnès; Graner, Edgard

    2017-02-01

    Fatty acid synthase (FASN) is responsible for the endogenous production of fatty acids from acetyl-CoA and malonyl-CoA. Its overexpression is associated with poor prognosis in human cancers including melanomas. Our group has previously shown that the inhibition of FASN with orlistat reduces spontaneous lymphatic metastasis in experimental B16-F10 melanomas, which is a consequence, at least in part, of the reduction of proliferation and induction of apoptosis. Here, we sought to investigate the effects of pharmacological FASN inhibition on lymphatic vessels by using cell culture and mouse models. The effects of FASN inhibitors cerulenin and orlistat on the proliferation, apoptosis, and migration of human lymphatic endothelial cells (HDLEC) were evaluated with in vitro models. The lymphatic outgrowth was evaluated by using a murine ex vivo assay. B16-F10 melanomas and surgical wounds were produced in the ears of C57Bl/6 and Balb-C mice, respectively, and their peripheral lymphatic vessels evaluated by fluorescent microlymphangiography. The secretion of vascular endothelial growth factor C and D (VEGF-C and -D) by melanoma cells was evaluated by ELISA and conditioned media used to study in vitro lymphangiogenesis. Here, we show that cerulenin and orlistat decrease the viability, proliferation, and migration of HDLEC cells. The volume of lymph node metastases from B16-F10 experimental melanomas was reduced by 39% in orlistat-treated animals as well as the expression of VEGF-C in these tissues. In addition, lymphatic vessels from orlistat-treated mice drained more efficiently the injected FITC-dextran. Orlistat and cerulenin reduced VEGF-C secretion and, increase production of VEGF-D by B16-F10 and SK-Mel-25 melanoma cells. Finally, reduced lymphatic cell extensions, were observed following the treatment with conditioned medium from cerulenin- and orlistat-treated B16-F10 cells. Altogether, our results show that FASN inhibitors have anti-metastatic effects by acting on

  8. The position- and lymphatic lumen-controlled tissue chambers to study live lymphatic vessels and surrounding tissues ex vivo.

    Science.gov (United States)

    Maejima, Daisuke; Nagai, Takashi; Bridenbaugh, Eric A; Cromer, Walter E; Gashev, Anatoliy A

    2014-09-01

    Until now, there has been no tool available to provide lymphatic researchers the ability to perform experiments in tissue explants containing lymphatic vessels under tissue position- and lymphatic lumen-controlled conditions. In this article we provide technical details and description of the method of using the newly developed and implemented the position- and lymphatic lumen-controlled tissue chambers to study live lymphatic vessels and surrounding tissues ex vivo. In this study, we, for the first time, performed detailed comparative analysis of the contractile and pumping activity of rat mesenteric lymphatic vessels (MLVs) situated within tissue explants mounted in new tissue chambers and isolated, cannulated, and pressurized rat MLVs maintained in isolated vessel setups. We found no significant differences of the effects of both transmural pressure- and wall shear stress sensitivities of MLVs in tissue chambers and isolated MLVs. We conclude that this new experimental tool, a position- and lymphatic lumen-controlled tissue chamber, allows precise investigation of lymphatic function of MLVs interacting with elements of the tissue microenvironment. This method provides an important new set of experimental tools to investigate lymphatic function.

  9. Vascular responses to radiotherapy and androgendeprivation therapy in experimental prostate cancer

    LENUS (Irish Health Repository)

    2012-05-23

    AbstractBackgroundRadiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC.MethodsUsing mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI.ResultsCompared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after

  10. Lymphatics and the breast

    Science.gov (United States)

    ... nodes are distributed at specific locations throughout the body. There is also an extensive network of lymphatic vessels in every woman's breast tissue, which is important in regulating the local fluid balance as well as in filtering out harmful substances. ...

  11. Role of Cox-2 in Vascular Inflammation: An Experimental Model of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Nicolás F. Renna

    2013-01-01

    Full Text Available The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n=8 each: control (W; W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR: WKY rats receiving 10% (w/v fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR: SHR receiving 10% (w/v fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases, VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

  12. 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.

  13. EXPERIMENTAL ACUTE NEPHRITIS: THE VASCULAR REACTIONS AND THE ELIMINATION OF NITROGEN

    Science.gov (United States)

    Pearce, Richard M.; Hill, Miner C.; Eisenbrey, Arthur B.

    1910-01-01

    By combining physiological and anatomical methods in the study of experimental nephritis it is possible to distinguish types of nephritis in which either tubular or vascular changes predominate, and are essentially characteristic of the lesion produced, but it is not possible to say that a given poison produces exclusively tubular or exclusively vascular lesions. The so-called epithelial poisons (potassium chromate, uranium nitrate and corrosive sublimate) present anatomical evidence of extensive tubular injury, and in the early stages show, on physiological study, no evidence of vascular injury other than exaggerated contraction and dilatation of the vessels and increased diuresis. On the other hand, the vascular poisons, arsenic and cantharidin, which produce but little injury to the tubules, tend to cause anuria and are characterized by minimal contraction and dilatation of the vessels and little or no flow of urine. From the physiological point of view these two types may be, for practical purposes, considered as examples of tubular and vascular nephritis. They are not, however, pure types; for the increased diuresis of the early tubular type is in itself evidence of vessel irritability and similar to the increased irritability caused by small doses of vascular poisons, and on the other hand, this essentially vascular lesion is accompanied by slight morphological changes in the tubular epithelium. Furthermore, the tubular lesions of chromium and uranium and corrosive sublimate pass into a stage closely resembling the vascular type, if not identical with it. Two forms of late tubular nephritis may be recognized. One of these, the anuric form, is accompanied by severe gastro-intestinal disturbance and evidence of approaching anuria; physiological tests show diminished power of dilatation of the vessels and corresponding inhibition of diuresis. The second form, the polyuric, is characterized by a condition of polyuria up to the moment of anesthesia; physiological

  14. Immunolocalization of lymphatic vessels in human fetal knee joint tissues.

    Science.gov (United States)

    Melrose, James; Little, Christopher B

    2010-08-01

    We immunolocalized lymphatic and vascular blood vessels in 12- and 14-week-old human fetal knee joint tissues using a polyclonal antibody to a lymphatic vascular endothelium specific hyaluronan receptor (LYVE-1) and a monoclonal antibody to podoplanin (mAb D2-40). A number of lymphatic vessels were identified in the stratified connective tissues surrounding the cartilaginous knee joint femoral and tibial rudiments. These tissues also contained small vascular vessels with entrapped red blood cells which were imaged using Nomarsky DIC microscopy. Neither vascular nor lymphatic vessels were present in the knee joint cartilaginous rudiments. The menisci in 12-week-old fetal knees were incompletely demarcated from the adjacent tibial and femoral cartilaginous rudiments which was consistent with the ongoing joint cavitation process at the femoral-tibial junction. At 14 weeks of age the menisci were independent structural entities; they contained a major central blood vessel containing red blood cells and numerous communicating vessels at the base of the menisci but no lymphatic vessels. In contrast to the 12-week-old menisci, the 14-week meniscal rudiments contained abundant CD-31 and CD-34 positive but no lymphatic vessels. Isolated 14-week-old meniscal cells also were stained with the CD-31 and CD 34 antibodies; CD-68 +ve cells, also abundant in the 14-week-old menisci, were detectable to a far lesser degree in the 12-week menisci and were totally absent from the femoral and tibial rudiments. The distribution of lymphatic vessels and tissue macrophages in the fetal joint tissues was consistent with their roles in the clearance of metabolic waste and extracellular matrix breakdown products arising from the rapidly remodelling knee joint tissues.

  15. The VEGF-C/VEGFR3 signaling pathway contributes to resolving chronic skin inflammation by activating lymphatic vessel function.

    Science.gov (United States)

    Hagura, Asami; Asai, Jun; Maruyama, Kazuichi; Takenaka, Hideya; Kinoshita, Shigeru; Katoh, Norito

    2014-02-01

    The functions of lymphatic vessels are to drain the protein-rich lymph from the extracellular space, to maintain normal tissue pressure, and to mediate the immune response, particularly in inflammatory conditions. To evaluate the function of the vascular endothelial growth factor (VEGF)-C/VEGF receptor (VEGFR)-3 signaling pathway in chronic skin inflammation. We used adenovirus-mediated VEGF-C or VEGFR3-immunoglobulin (Ig) production and investigated the effects of VEGF-C/VEGFR3 signaling on the resolution of inflammation using the experimental chronic contact hypersensitivity (CHS) reaction mouse model. VEGF-C gene transfer promoted significant reduction of ear swelling and ear weight in CHS reaction-induced skin inflammation. Although, there was no significant difference in the number of lymphatic vessels, the number of infiltrating CD11b-positive inflammatory cells was significantly reduced in the VEGF-C group, which suggested that VEGF-C upregulated the drainage of interstitial fluid and inflammatory cells via lymphatic vessels. Furthermore, blockade of VEGFR3 expression resulted in a significant delay in the recovery from CHS reaction-induced skin inflammation. Lymphatic vessel size was enlarged and a significant increase of infiltrating CD11b inflammatory cells was observed in mice with VEGFR3-Ig gene transfer compared to control mice. These results suggested that blockade of VEGFR3 inhibited the drainage function of the lymphatic system. This study provides evidence that VEGF-C/VEGFR3 signaling plays an important role in the resolution of skin inflammation; the regulation of lymphatic function may have a great therapeutic potential in inflammatory skin diseases. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Smooth muscle–endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation

    Science.gov (United States)

    Lutter, Sophie; Xie, Sherry; Tatin, Florence

    2012-01-01

    Active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly and lymphatic pumping are poorly understood. Here, we identify Reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as an important regulator of lymphatic vascular development. Reelin-deficient mice showed abnormal collecting lymphatic vessels, characterized by a reduced number of SMCs, abnormal expression of lymphatic capillary marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and impaired function. Furthermore, we show that SMC recruitment to lymphatic vessels stimulated release and proteolytic processing of endothelium-derived Reelin. Lymphatic endothelial cells in turn responded to Reelin by up-regulating monocyte chemotactic protein 1 (MCP1) expression, which suggests an autocrine mechanism for Reelin-mediated control of endothelial factor expression upstream of SMC recruitment. These results uncover a mechanism by which Reelin signaling is activated by communication between the two cell types of the collecting lymphatic vessels—smooth muscle and endothelial cells—and highlight a hitherto unrecognized and important function for SMCs in lymphatic vessel morphogenesis and function. PMID:22665518

  17. Lymphatic vessels in human eyelids: an immunohistological study in dermatochalasis and chalazion.

    Science.gov (United States)

    Aglianó, M; Lorenzoni, P; Volpi, N; Massai, L; Carbotti, P; Fruschelli, M; Muscettola, M; Alessandrini, C; Grasso, G

    2008-03-01

    We investigated lymphatic morphology and expression of endothelin (ET-1) axis molecules in human eyelids affected by an inflammatory state (chalazion) and an age-related degenerative condition (dermatochalasis). Lymphatics were immunohistologically detected by D2-40/LYVE-1 staining. Absorbing lymphatic vessels were localized in papillary dermis and around skin appendages with distinctive morphology. In chalazion, D2-40 reactive flattened lymphatic profiles were compressed by inflammatory infiltrate; in dermatochalasis, large fully opened lymphatics were observed, with a significantly wider total area (lymphatic lumina/200x field; p < 0.05). The lymphatic density (number/200x field) in the two groups was within the same range. Lymphatic dilation is possibly dependent on reduction and fragmentation of the dermal elastic network as well as of oxytalanic fibers in the papillary dermis of dermatochalasis, as shown by Weigert's reaction. Multifunctional peptide ET-1, involved in vasomotion, inflammation and connective proliferation, was faintly and discontinuously localized on lymphatics, as was its type A receptor. In contrast, the consistent expression of type B receptor indicates that lymphatic endothelium is a physiological target for ET-1, whose effects are modulated by multiple pathophysiological conditions. Thus, vasoactive factors play a role in the physiology of richly vascularized eyelids, and therefore, morphofunctional characterization of lymphatic vessels may be useful in suggesting treatment options.

  18. What Is the Lymphatic System?

    Science.gov (United States)

    ... 2017 NLN International Conference What is the Lymphatic System? To better understand lymphedema , we first must understand the normal lymphatic system (see diagram) . This system functions parallel to the ...

  19. Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals.

    Science.gov (United States)

    AlGhamdi, Khalid M; Kumar, Ashok; Ashour, Abdelkader E; Al-Rikabi, Ammar C; AlOmrani, Abdullah Hasan; Ahamed, Shaik Shaffi

    2017-01-01

    Varicose veins and the complications of venous disease are common disorders in humans. To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Relatively small number of experimental animals used. This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

  20. Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model.

    Science.gov (United States)

    Lokmic, Zerina; Mitchell, Geraldine M; Koh Wee Chong, Nicholas; Bastiaanse, Jacqueline; Gerrand, Yi-Wen; Zeng, Yiping; Williams, Elizabeth D; Penington, Anthony J

    2014-01-01

    Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34(Neg)CD31(Pos) LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34(Neg)CD31(Pos) lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (P lymphatic malformations.

  1. Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life

    Science.gov (United States)

    Hess, Paul R.; Rawnsley, David R.; Jakus, Zoltán; Yang, Yiqing; Sweet, Daniel T.; Fu, Jianxin; Herzog, Brett; Lu, MinMin; Nieswandt, Bernhard; Oliver, Guillermo; Makinen, Taija; Xia, Lijun; Kahn, Mark L.

    2013-01-01

    Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life. PMID:24292710

  2. Bone ingrowth and vascular supply in experimental spinal fusion with platelet-rich plasma.

    Science.gov (United States)

    Cinotti, Gianluca; Corsi, Alessandro; Sacchetti, Benedetto; Riminucci, Mara; Bianco, Paolo; Giannicola, Giuseppe

    2013-03-01

    Prospective investigation using a posterolateral spinal fusion (PLSF) model in rabbits. To assess the effects of platelet-rich plasma (PRP) alone, or with uncultured bone marrow, on bone ingrowth and angiogenesis in experimental PLSF. PRP is an autologous substance potentially beneficial to spinal fusion, because it includes several growth factors that may stimulate bone ingrowth and angiogenesis. However, the results of experimental and clinical investigations on the effectiveness of PRP in spinal fusion are controversial. This study was aimed at analyzing the influence of PRP on bone ingrowth and angiogenesis in experimental PLSF. Twenty White New Zealand rabbits underwent PLSF at L4-L5 level. The graft material included a ceramic carrier (Pro-Osteon 500R) loaded, in 7 rabbits, with PRP alone on the right side (group 1A) and with uncultured bone marrow in the left side (group 1B). In 7 rabbits, the ceramic carrier was used alone in the right side (group 2A), and with uncultured bone marrow in the left side (group 2B). Six rabbits (group 3) were sham operated on both right and left sides. Six months after surgery, the lumbar spine was harvested en bloc and evaluated by high-resolution radiographs (Faxitron, Wheeling, IL) and histology. The radiographical outcome showed a fusion rate of 86% in groups 1A, 1B, and 2B and a fusion rate of 71% in group 2A. No specimen showed a solid fusion in the sham group. Histological analysis revealed new bone formation in the periapophyseal area in groups 1 and 2, but a complete bony bridge between the transverse processes was not observed in any specimen. In all groups, vascular density was significantly greater in the peri- compared with the interapophyseal region. In the PRP group, there was no evidence of increased vascular density in the grafted material compared with the other groups. In experimental PLSF model in rabbits, PRP was not effective in promoting new bone formation and vascularization.

  3. Lymphatics in Human Lymphatic Filariasis: In Vitro Models of Parasite-Induced Lymphatic Remodeling

    OpenAIRE

    Bennuru, Sasisekhar; Thomas B Nutman

    2009-01-01

    Lymphatic filariasis characterized by the dysfunction of the lymphatics can lead to severe (and often) irreversible lymphedema and elephantiasis. Decades of research in the field shows that the establishment of the adult parasites in the lymphatics triggers a cascade of events that ultimately results in tissue scarring and fibrosis. In this minireview, we focus on the studies addressing the mechanisms underlying the parasite-induced lymphatic dilatation that suggests parasite-induced lymphati...

  4. 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.

  5. Lymphatic Vascular-Based Therapy for IBD

    Science.gov (United States)

    2012-07-01

    R.N.Van, H.Takenaka, P.A.D’Amore, J.Stein-Streilein, D.W.Losordo, J.W.Streilein, Inflammation-induced lymphangiogenesis in the cornea arises from...lymph node dissection and transplantation Nat.Med. 13, (2007) 1458-1466. [31] L.Kopfstein, T.Veikkola, V.G.Djonov, V.Baeriswyl, T.Schomber

  6. Myeloid Wnt ligands are required for normal development of dermal lymphatic vasculature.

    Directory of Open Access Journals (Sweden)

    Ajit Muley

    Full Text Available Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter Wntless we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics. As lymphatic progenitors are emigrating from the cardinal vein and intersomitic vessels, myeloid Wnt ligands regulate both their numbers and migration distance. Later in lymphatic development, myeloid Wnt ligands regulate proliferation of lymphatic endothelial cells (LEC and thus control lymphatic vessel caliber. Myeloid-specific deletion of WNT co-receptor Lrp5 or Wnt5a gain-of-function also produce elevated caliber in dermal lymphatic capillaries. These data thus suggest that myeloid cells produce Wnt ligands to regulate lymphatic development and use Wnt pathway co-receptors to regulate the balance of Wnt ligand activity during the macrophage-LEC interaction.

  7. Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes.

    Science.gov (United States)

    Bianchi, Roberta; Russo, Erica; Bachmann, Samia B; Proulx, Steven T; Sesartic, Marko; Smaadahl, Nora; Watson, Steve P; Buckley, Christopher D; Halin, Cornelia; Detmar, Michael

    2017-01-01

    The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels. We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn(ΔLEC)) and induced gene deletion postnatally. Pdpn(ΔLEC) mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn(ΔLEC) mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn(ΔLEC) mice. These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes. © 2016 American Heart Association, Inc.

  8. Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

    Science.gov (United States)

    Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

    2017-01-01

    This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

  9. Lymphatic Leukaemia* In Acute

    African Journals Online (AJOL)

    A case report of a patient who developed fatal pneumo- cystis pneumonia while in remission from acute lymphatic ... Chagas and CariniY This rare and usually fatal disease occurs in young babies;" or in individuals whose ... was then a month since his illness had started. On admission to our clinic we found the following: ...

  10. Pleural function and lymphatics.

    Science.gov (United States)

    Negrini, D; Moriondo, A

    2013-02-01

    The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung-chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co-operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  11. Progressive loss of lymphatic vessels in skin of patients with systemic sclerosis.

    Science.gov (United States)

    Manetti, Mirko; Milia, Anna Franca; Guiducci, Serena; Romano, Eloisa; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

    2011-02-01

    Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular and fibrotic changes in the skin and internal organs. The role of blood vessel dysfunction in the pathogenesis of SSc has been extensively investigated, but few studies have addressed the involvement of the lymphatic vascular system. Our aim was to evaluate dermal lymphatic vessels in patients with SSc according to different phases of skin involvement. Skin biopsies were obtained from the forearm of 25 SSc patients (10 early/15 late-stage disease) and 13 healthy controls. Skin sections were immunostained for podoplanin (D2-40), which is selectively expressed in lymphatic endothelial cells, and examined by confocal laser scanning microscopy. Lymphatic vessels were counted in the papillary and reticular dermis. Data were analyzed using Student's t test. The number of lymphatic vessels was significantly reduced in the papillary and reticular dermis of SSc patients compared with controls. In early SSc, lymphatic vessel counts were not different from controls in the papillary dermis, and showed a trend toward a reduction in the reticular dermis. In late SSc, a significant reduction in lymphatic vessels compared with controls was found in both the papillary and reticular dermis. The number of lymphatic vessels in the papillary dermis of late SSc was significantly lower than in early SSc. In SSc, lymphatic microangiopathy is linked to the progression of skin involvement. The progressive disappearance of lymphatic vessels may have a critical pathogenetic role in the progression of SSc from an early edematous phase to overt fibrosis.

  12. Polyhydroxybutyrate/valerate/polycaprolactone small-diameter vascular graft: Experimental study of integration into organism

    Science.gov (United States)

    Antonova, L. V.; Burago, A. Yu.; Mironov, A. V.; Matveeva, V. G.; Velikanova, E. A.; Mukhamadiyarov, R. A.; Glushkova, T. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S.

    2015-10-01

    We prepared polyhydroxybutyrate/valerate (PHBV)/polylcaprolactone (PCL) small-diameter vascular grafts using electrospinning. Surface structure was assessed by scanning electron microscopy whilst physicomechanical properties were investigated by longitudinal uniaxial tension testing. Patency of grafts implanted into the rat abdominal aorta was evaluated using a Doppler ultrasonography at 2 week, 1 month and 12 month postimplantation. In addition, we assessed local histological features, along with IL-1β, IL-2, IL-4, IL-10, TNFa, TGF-β1, and VEGF serum levels. We revealed that only 2 (25%) grafts were not thrombosed at 2 week and 1 month postimplantation. However, at 12 month postimplantation a satisfactory histological pattern was observed in 50% of all cases, and we detected a monolayer of endothelial cells on the inner graft surface in half the cases. Regarding other grafts, we revealed minor connective tissue hyperplasia in 41.7% of the grafts and an inflammatory infiltrate in the part of the arterial wall in 8.3% of the grafts. We found that the IL-1β serum level was 3.5-fold higher in the group of experimental rats at 12 month postimplantation (p IL-10 serum level at 1 and 12 month postimplantation was more than 100-fold higher in comparison with 2 week postimplantation and control rats (p < 0.001). Serum VEGF was detected only at 12 month postimplantation. All in all, we created a biocompatible PHBV/PCL small-diameter vascular graft with a high surface area to volume ratio. A long-term patency of biodegradable vascular grafts after implantation into the rat abdominal aorta and the absence of a considerable immune response confirmed a high biocompatibility of such construct and the possibility of its use as a vascular graft.

  13. 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...... methods for use with commercially available quantum dots and discuss common difficulties....

  14. Lymphatics in human lymphatic filariasis: in vitro models of parasite-induced lymphatic remodeling.

    Science.gov (United States)

    Bennuru, Sasisekhar; Nutman, Thomas B

    2009-12-01

    Lymphatic filariasis characterized by the dysfunction of the lymphatics can lead to severe (and often) irreversible lymphedema and elephantiasis. Decades of research in the field shows that the establishment of the adult parasites in the lymphatics triggers a cascade of events that ultimately results in tissue scarring and fibrosis. In this minireview, we focus on the studies addressing the mechanisms underlying the parasite-induced lymphatic dilatation that suggests parasite-induced lymphatic remodeling and lymphangiogenesis may be the prelude towards developing chronic and irreversible filarial pathology.

  15. Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals*

    Science.gov (United States)

    AlGhamdi, Khalid M; Kumar, Ashok; Ashour, Abdelkader E.; AL-Rikabi, Ammar C.; AlOmrani, Abdullah Hasan; Ahamed, Shaik Shaffi

    2017-01-01

    Background Varicose veins and the complications of venous disease are common disorders in humans. Objective To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Methods Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Results Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Study limitations Relatively small number of experimental animals used. Conclusions This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent. PMID:28954096

  16. Intercellular ultrafast Ca2+ wave in vascular smooth muscle cells: numerical and experimental study

    Science.gov (United States)

    Quijano, J. C.; Raynaud, F.; Nguyen, D.; Piacentini, N.; Meister, J. J.

    2016-08-01

    Vascular smooth muscle cells exhibit intercellular Ca2+ waves in response to local mechanical or KCl stimulation. Recently, a new type of intercellular Ca2+ wave was observed in vitro in a linear arrangement of smooth muscle cells. The intercellular wave was denominated ultrafast Ca2+ wave and it was suggested to be the result of the interplay between membrane potential and Ca2+ dynamics which depended on influx of extracellular Ca2+, cell membrane depolarization and its intercel- lular propagation. In the present study we measured experimentally the conduction velocity of the membrane depolarization and performed simulations of the ultrafast Ca2+ wave along coupled smooth muscle cells. Numerical results reproduced a wide spectrum of experimental observations, including Ca2+ wave velocity, electrotonic membrane depolarization along the network, effects of inhibitors and independence of the Ca2+ wave speed on the intracellular stores. The numerical data also provided new physiological insights suggesting ranges of crucial model parameters that may be altered experimentally and that could significantly affect wave kinetics allowing the modulation of the wave characteristics experimentally. Numerical and experimental results supported the hypothesis that the propagation of membrane depolarization acts as an intercellular messenger mediating intercellular ultrafast Ca2+ waves in smooth muscle cells.

  17. Development and plasticity of meningeal lymphatic vessels.

    Science.gov (United States)

    Antila, Salli; Karaman, Sinem; Nurmi, Harri; Airavaara, Mikko; Voutilainen, Merja H; Mathivet, Thomas; Chilov, Dmitri; Li, Zhilin; Koppinen, Tapani; Park, Jun-Hee; Fang, Shentong; Aspelund, Aleksanteri; Saarma, Mart; Eichmann, Anne; Thomas, Jean-Léon; Alitalo, Kari

    2017-11-15

    The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS. © 2017 Antila et al.

  18. [Mixed facial lymphatic malformation: case report].

    Science.gov (United States)

    Morovic I, Carmen Gloria; Vidal T, Claudia; Leiva V, Noemí; Véliz M, Sebastián

    2014-12-01

    Lymphangiomas are a common form of vascular malformation of the lymphatic vessels, mainly in the head and neck region. Most cases are progressive evolution and require a multidisciplinary approach. Currently, the first therapeutic option is sclerotherapy, leaving surgery for the treatment of remaining lesions. To present a case of facial lymphatic malformation (LM) treated with sclerotherapy, surgery and orthodontics in a 15-year follow up. A one-year-old female patient who consulted health professionals due to a progressive volume increase of the soft parts of her right cheek. The imaging study confirmed the diagnosis of microcystic lymphatic malformation. It was managed with OK-432 sclerotherapy and Bleomycin. At 2 years of age, the patient response was considered adequate; an intralesional submandibular surgical excision was then performed, with partial resection of the lesion. The biopsy confirmed the diagnosis of microcystic LM. Six months after, a re-resection was planned using the same approach and removing the remaining lesion, with favorable development until the age of 9 years when the patient required surgery and orthodontic management due to intraoral recurrence. No major developments until the age of 13 when a new orthodontic surgery and handling are planned to perform right oral commissure suspension. LM management by sclerotherapy, surgery, and orthodontics has shown the advantages of a multidisciplinary long-term treatment in this case.

  19. 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.

  20. Malformation lymphatic abdominal

    OpenAIRE

    Sebastião Ribeiro do Carmo Filho; Poliana de Paula Vieira Borges dos Reis Soares; Fabiano Souza Soares; Erivanea Garcia Ribeiro; Willy Pereira da Silva Filho; Rafael Naves Tomás; Yara Rocha Ximenes

    2015-01-01

    Abdominal lymphangiomas are benign malformations of the lymphatic system. The diagnosis is established due to patient's clinical manifestations associated with imaging. The clinical presentation of cystic lymphangiomas is much variable and depends on the symptoms, mostly caused by the abdominal mass, it´s size and location. It is accepted that the incidence of mesenteric cysts in the american population is somehow between 1:100.000 and 1:250.000, causing hospital admissions. Surgical treatmen...

  1. Lymphatic filariasis and onchocerciasis.

    Science.gov (United States)

    Taylor, Mark J; Hoerauf, Achim; Bockarie, Moses

    2010-10-02

    Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis. Most filarial species that infect people co-exist in mutualistic symbiosis with Wolbachia bacteria, which are essential for growth, development, and survival of their nematode hosts. These endosymbionts contribute to inflammatory disease pathogenesis and are a target for doxycycline therapy, which delivers macrofilaricidal activity, improves pathological outcomes, and is effective as monotherapy. Drugs to treat filariasis include diethylcarbamazine, ivermectin, and albendazole, which are used mostly in combination to reduce microfilariae in blood (lymphatic filariasis) and skin (onchocerciasis). Global programmes for control and elimination have been developed to provide sustained delivery of drugs to affected communities to interrupt transmission of disease and ultimately eliminate this burden on public health. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. [Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension].

    Science.gov (United States)

    Zhang, Shujuan; Zhao, Qingyan; Jiang, Xuejun; Yang, Bo; Dai, Zixuan; Wang, Xiaozhan; Wang, Xule; Guo, Zongwen; Yu, Shengbo; Tang, Yanhong; Hu, Wei; Huang, Congxin

    2015-04-14

    To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH). According to the random number table, 24 beagles were randomized into control, PAH and PAH+RSD groups (n=8 each). The levels of neurohormone, echocardiogram and dynamics parameters were measured. Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH+RSD groups) were injected. The PAH+RSD group underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. The values of right ventricular systolic pressure (RVSP) and pulmonary arterial systolic pressure (PASP) in PAH and PAH+RSD groups were both significantly higher than those in control group ((42.8±8.7), (30.8±6.8) vs (23.2±5.7) mmHg (1 mmHg=0.133 kPa) and (45.1±11.2), (32.6±7.9) vs (24.7±7.1) mmHg). Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH+RSD group (all PRSD group ((46±8) and (67±9) pg/ml) (all PRSD dogs. RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.

  3. Promotion of lymphatic integrity by angiopoietin-1/Tie2 signaling during inflammation.

    Science.gov (United States)

    Kajiya, Kentaro; Kidoya, Hiroyasu; Sawane, Mika; Matsumoto-Okazaki, Yuuko; Yamanishi, Haruyo; Furuse, Mikio; Takakura, Nobuyuki

    2012-03-01

    The cutaneous lymphatic system plays a major role in tissue fluid homeostasis and inflammation of the skin. Although several lymphangiogenic factors are known to be involved in the formation of lymphatic vessels, the molecular mechanisms that maintain lymphatic integrity and control the functional drainage of interstitial fluid and resolution of inflammation remain unknown. Here we show that angiopoietin-1 (Ang1) enhances lymphatic integrity and function during inflammation. Ang1 transgenic mice under the control of keratin-14 (K14-Ang1) showed attenuated edema formation and inflammation after UV B (UVB) exposure. After UVB irradiation, blood vascular permeability was inhibited in K14-Ang1 mice compared with wild-type (WT) mice. Moreover, lymphatic vessels of WT mice were markedly enlarged and leaky in inflamed skin, whereas K14-Ang1 mice showed relatively contracted lymphatic vessels together with enhanced lymphatic vascularization. Expression of endothelial-specific tight junction molecules claudin-5 and zonula occludens protein 1 (ZO-1) was strongly down-regulated in the inflamed lymphatic vessels of UVB-exposed WT mice, whereas down-regulation of both claudin-5 and ZO-1 was blocked in UVB-exposed K14-Ang1 mice. In vitro studies revealed that the stability of lymphatic endothelial cells was enhanced in the presence of Ang1, presumably via up-regulation of claudin-5, as well as ZO-1. Claudin-5 knockdown markedly increased the permeability of lymphatic endothelial cells. Overall, our data strongly support the idea that Ang1/Tie2 signaling promotes lymphatic integrity by modulating tight junction molecule expression during inflammation. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Photoacoustic imaging of lymphatic pumping

    Science.gov (United States)

    Forbrich, Alex; Heinmiller, Andrew; Zemp, Roger J.

    2017-10-01

    The lymphatic system is responsible for fluid homeostasis and immune cell trafficking and has been implicated in several diseases, including obesity, diabetes, and cancer metastasis. Despite its importance, the lack of suitable in vivo imaging techniques has hampered our understanding of the lymphatic system. This is, in part, due to the limited contrast of lymphatic fluids and structures. Photoacoustic imaging, in combination with optically absorbing dyes or nanoparticles, has great potential for noninvasively visualizing the lymphatic vessels deep in tissues. Multispectral photoacoustic imaging is capable of separating the components; however, the slow wavelength switching speed of most laser systems is inadequate for imaging lymphatic pumping without motion artifacts being introduced into the processed images. We investigate two approaches for visualizing lymphatic processes in vivo. First, single-wavelength differential photoacoustic imaging is used to visualize lymphatic pumping in the hindlimb of a mouse in real time. Second, a fast-switching multiwavelength photoacoustic imaging system was used to assess the propulsion profile of dyes through the lymphatics in real time. These approaches may have profound impacts in noninvasively characterizing and investigating the lymphatic system.

  5. Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension

    Science.gov (United States)

    Christou, Helen; Reslan, Ossama M.; Mam, Virak; Tanbe, Alain F.; Vitali, Sally H.; Touma, Marlin; Arons, Elena; Mitsialis, S. Alex; Kourembanas, Stella

    2012-01-01

    Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening

  6. Polyhydroxybutyrate/valerate/polycaprolactone small-diameter vascular graft: Experimental study of integration into organism

    Energy Technology Data Exchange (ETDEWEB)

    Antonova, L. V., E-mail: antonova.la@mail.ru; Burago, A. Yu.; Matveeva, V. G.; Velikanova, E. A.; Mukhamadiyarov, R. A.; Glushkova, T. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo (Russian Federation); Mironov, A. V. [Kemerovo Cardiology Dispensary, Kemerovo (Russian Federation)

    2015-10-27

    We prepared polyhydroxybutyrate/valerate (PHBV)/polylcaprolactone (PCL) small-diameter vascular grafts using electrospinning. Surface structure was assessed by scanning electron microscopy whilst physicomechanical properties were investigated by longitudinal uniaxial tension testing. Patency of grafts implanted into the rat abdominal aorta was evaluated using a Doppler ultrasonography at 2 week, 1 month and 12 month postimplantation. In addition, we assessed local histological features, along with IL-1β, IL-2, IL-4, IL-10, TNFa, TGF-β1, and VEGF serum levels. We revealed that only 2 (25%) grafts were not thrombosed at 2 week and 1 month postimplantation. However, at 12 month postimplantation a satisfactory histological pattern was observed in 50% of all cases, and we detected a monolayer of endothelial cells on the inner graft surface in half the cases. Regarding other grafts, we revealed minor connective tissue hyperplasia in 41.7% of the grafts and an inflammatory infiltrate in the part of the arterial wall in 8.3% of the grafts. We found that the IL-1β serum level was 3.5-fold higher in the group of experimental rats at 12 month postimplantation (p < 0.01). In addition, the IL-2 and IL-4 serum levels at 12 month postimplantation were 2- and 2.8-fold higher as compared to short-term implantation (2 weeks and 1 month) and control rats (p < 0.05) whilst the IL-10 serum level at 1 and 12 month postimplantation was more than 100-fold higher in comparison with 2 week postimplantation and control rats (p < 0.001). Serum VEGF was detected only at 12 month postimplantation. All in all, we created a biocompatible PHBV/PCL small-diameter vascular graft with a high surface area to volume ratio. A long-term patency of biodegradable vascular grafts after implantation into the rat abdominal aorta and the absence of a considerable immune response confirmed a high biocompatibility of such construct and the possibility of its use as a vascular graft.

  7. A Tale of Two Models: Mouse and Zebrafish as Complementary Models for Lymphatic Studies

    Science.gov (United States)

    Kim, Jun-Dae; Jin, Suk-Won

    2014-01-01

    Lymphatic vessels provide essential roles in maintaining fluid homeostasis and lipid absorption. Dysfunctions of the lymphatic vessels lead to debilitating pathological conditions, collectively known as lymphedema. In addition, lymphatic vessels are a critical moderator for the onset and progression of diverse human diseases including metastatic cancer and obesity. Despite their clinical importance, there is no currently effective pharmacological therapy to regulate functions of lymphatic vessels. Recent efforts to manipulate the Vascular Endothelial Growth Factor-C (VEGFC) pathway, which is arguably the most important signaling pathway regulating lymphatic endothelial cells, to alleviate lymphedema yielded largely mixed results, necessitating identification of new targetable signaling pathways for therapeutic intervention for lymphedema. Zebrafish, a relatively new model system to investigate lymphatic biology, appears to be an ideal model to identify novel therapeutic targets for lymphatic biology. In this review, we will provide an overview of our current understanding of the lymphatic vessels in vertebrates, and discuss zebrafish as a promising in vivo model to study lymphatic vessels. PMID:24854860

  8. Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Jain, Swati; Sharma, Bhupesh

    2016-10-01

    Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Update on osteopathic medical concepts and the lymphatic system.

    Science.gov (United States)

    Degenhardt, B F; Kuchera, M L

    1996-02-01

    The osteopathic medical profession has long recognized the importance of the lymphatic system in maintaining health. A review of scientific studies shows much information on the mechanisms and importance of lymph circulation. Many osteopathic manipulative techniques designed to treat patients with tissue congestion are based on early research recognizing that lymph flow is influenced by myofascial compression. Osteopathic manipulative treatment of the diaphragm was substantiated when pressure differentials created by the thoracic diaphragm were shown to influence lymph flow. Current research demonstrates that autonomically mediated, intrinsic lymphatic contractility plays a significant role in lymph propulsion, supporting the use of osteopathic manipulative techniques directed at influencing the autonomic nervous system to improve lymphatic circulation. Although research provides an explanation of how osteopathic manipulative techniques influence the lymphatic system, experimentation to test the direct influence of manipulation on lymph circulation is needed. Clinical outcomes studies are also necessary to substantiate the clinical efficacy of osteopathic manipulative techniques.

  10. Experimental investigation of the early interaction between cyanobacterial soil crusts and vascular plants

    Science.gov (United States)

    Klemens Zaplata, Markus; Veste, Maik; Pohle, Ina; Schümberg, Sabine; Abreu Schonert, Iballa; Hinz, Christoph

    2016-04-01

    While there are hints that biological soil crusts (BSCs) can constitute physical barriers for the emergence of vascular plants, a conceptual approach for the quantitative evaluation of these effects is still missing. Here we present an experimental design to test the emergence of seedlings in situ with (i) capping natural intact, (ii) destroyed and (iii) removed BSC. The selected field site is directly adjacent to the constructed Hühnerwasser catchment (Lusatia, Germany). This site exists since the end of 2008 and consists of loamy sand. Serving as proxy for seedling thrust, we inserted pre-germinated seeds of three confamiliar plant species with different seed masses (members of the Fabaceae family: Lotus corniculatus L., Ornithopus sativus Brot., and Glycine max (L.) Merr.). In each treatment as well as in the control group planting depths were 10 mm. We took care that experimental plots had identical crust thickness, slightly less than 4 mm, serving as proxy for mechanical resistance. A plot became established as follows: Firstly, the pristine crusted surface was vertically cut. To the windward side the BSC remained intact (i: "with BSC" stripe). To the downwind side soil material was temporarily excavated for laterally inserting the seeds beneath the surface of the first stripe. Then at the thereby disturbed second stripe pulverised BSC material became filled as a top layer (ii: "BSC mix" stripe). From the next stripe the BSC was removed (iii: "no BSC" stripe). Thus each plot had each experimental group in spatial contiguity (within 50 cm × 50 cm). The overall 50 plots were distributed across an area of 40 m × 12 m. When individuals of a species either emerged at all stripes, "× × ×", or at no stripe of a plot, "- - -", there was no reason to suppose any effect of a crust. The "- × ×" emergence pattern (depicting the appearance of seedlings in both stripes possessing manipulated surfaces) points towards hindrance more clearly than "- × -" or "- -

  11. Experimental results and clinical impact of using autologous rectus fascia sheath for vascular replacement

    NARCIS (Netherlands)

    Kobori, Laszlo; Nemeth, Tibor; Nagy, Peter; Dallos, Gabor; Sotonyi, Peter; Fehervari, Imre; Nemes, Balazs; Gorog, Denes; Patonai, Attila; Monostory, Katalin; Doros, Attila; Sarvary, Enikoe; Fazakas, Janos; Gerlei, Zsuzsanna; Benkoe, Tamas; Piros, Laszlo; Jaray, Jeno; De Jong, Koert P.

    Vascular complications are major causes of graft failure in liver transplantation. The use of different vascular grafts is common but the results are controversial. The aim of this study was to create an 'ideal' arterial interponate for vascular replacements in the clinical field. An autologous,

  12. Lymphatic vessels: an emerging actor in atherosclerotic plaque development.

    Science.gov (United States)

    Kutkut, Issa; Meens, Merlijn J; McKee, Thomas A; Bochaton-Piallat, Marie-Luce; Kwak, Brenda R

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is critical for processes that are intimately linked to atherogenesis such as the immune response and cholesterol metabolism. However, whether lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less clear despite increasing research efforts in this field. PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications. Current knowledge about lymphatic vessels in the arterial wall came from studies that examined the presence and location of such vessels in human atherosclerotic plaque specimens, as well as in a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs, rats and mice). Generally, three experimental approaches have been used to investigate the functional role of plaque-associated lymphatic vessels; experimental lymphostasis was used to investigate lymphatic drainage of the arterial wall, and more recently, studies with genetic interventions and/or surgical transplantation have been performed. Lymphatic vessels seem to be mostly present in the adventitial layer of the arterial walls of animals and humans. They are involved in reverse cholesterol transport from atherosclerotic lesions, and arteries with a dense lymphatic network seem naturally protected against atherosclerosis. Lymphangiogenesis is a process that is an important part of the inflammatory loop in atherosclerosis. However, how augmenting or impeding the distribution of lymphatic vessels impacts disease progression remains to be investigated in future studies. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Experimental diabetes induces structural, inflammatory and vascular changes of Achilles tendons.

    Directory of Open Access Journals (Sweden)

    Rodrigo R de Oliveira

    Full Text Available This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS and nitrate and nitrite level. The Achilles tendon thickness (µm/100g of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98 vessels/field when compared to the control group 0.89 (1.68 vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18 vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99 vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy.

  14. Malformation lymphatic abdominal

    Directory of Open Access Journals (Sweden)

    Sebastião Ribeiro do Carmo Filho

    2015-06-01

    Full Text Available Abdominal lymphangiomas are benign malformations of the lymphatic system. The diagnosis is established due to patient's clinical manifestations associated with imaging. The clinical presentation of cystic lymphangiomas is much variable and depends on the symptoms, mostly caused by the abdominal mass, it´s size and location. It is accepted that the incidence of mesenteric cysts in the american population is somehow between 1:100.000 and 1:250.000, causing hospital admissions. Surgical treatment, in most cases, has good prognosis. This procedure is followed by the necessary resection, biopsy and cytology of the mass.

  15. 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 this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP)....

  16. Vascularization of the kidney of the ground squirrel (Citellus citellus in comparison with other experimental animals

    Directory of Open Access Journals (Sweden)

    Blagojević Miloš

    2015-01-01

    Full Text Available Ground squirrel is the only representative of its genus in our country. As experimental animal is used in microbiology, parasitology, immunology and pharmacology. The aim of this study was to examine a part of ground squirrel cardiovascular system and thus help better understanding of anatomy of the body of this specific animal as well as to contribute to comparative anatomy. The studies were perfomed on six ground squirrels, both sexes, weight between 200- 300 g. In order to obtain the arterial vascularization of the kidney, contrast mass gelatin stained with painting tempera was injected into the abdominal aorta after bleeding out. After the injection, blood vessels were prepared and photographed. Corosive preparations of the vein blood vessels of the kidneys were obtained by injection of Byocril into the right azygos vein after bleeding out. After injection, the preparations were placed into 5% NaOH for 96 hours or 10% NaOH for 48 hours. After that the preparations were rinsed with hot water and photographed. A. renalis dextra arises from the lateral wall of the abdominal aorta, 3-4 mm caudal to A. mesenterica cranialis. In most cases, this vessel divides into two or three branches before entering the hilus of the right kidney. A. renalis sinistra arises from the lateral wall of the abdominal aorta, 7-9 mm caudal to the right renal artery. Often, instead of one left renal artery, there are two, rarely three. Based on the results of our study, we concluded that in ground squirrel there is one A. renalis dextra and often two, rarely three Aa. renales sinistrae. In renal venous vascularization, both right and left renal vein are involved. Before entering the kidney, both of them divide into cranial and caudal branch, undergoing renal hilus, enter the renal sinus and continues to branch out into smaller branches.

  17. Evaluation and management of peripheral venous and lymphatic malformations.

    Science.gov (United States)

    Nassiri, Naiem; Thomas, Jones; Cirillo-Penn, Nolan C

    2016-04-01

    The International Society for Study of Vascular Anomalies (ISSVA) broadly categorizes vascular anomalies as vascular tumors or vascular malformations. The latter are congenital lesions that are further categorized by their flow properties and include high-flow arteriovenous malformations, slow-flow venous and lymphatic malformations, and congenital mixed syndromes, which can include a combination of malformations. Unlike vascular tumors, vascular malformations never regress and can persist and grow for the duration of the patient's lifespan. As our understanding of the natural history, hemodynamics, and treatment outcomes of these lesions has expanded and evolved over the last few decades, certain fundamental diagnostic and therapeutic principles have been established and are considered standard of care. These overarching principles are crucial to adhere to in the overall management of these lesions and are highlighted and expanded on in this report, which focuses exclusively on peripheral slow-flow venous and lymphatic malformations. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  18. Dermal lymphatic dilation in a mouse model of alopecia areata

    Science.gov (United States)

    Sundberg, John P.; Pratt, C. Herbert; Silva, Kathleen A.; Kennedy, Victoria E.; Stearns, Timothy; Sundberg, Beth A.; King, Lloyd E.; HogenEsch, Harm

    2016-01-01

    Mouse models of various types of inflammatory skin disease are often accompanied by increased dermal angiogenesis. The C3H/HeJ inbred strain spontaneously develops alopecia areata (AA), a cell mediated autoimmune disorder that can be controllably expanded using full thickness skin grafts to young unaffected mice. This provides a reproducible and progressive model for AA in which the vascularization of the skin can be examined. Mice receiving skin grafts from AA or normal mice were evaluated at 5, 10, 15, and 20 weeks after engraftment. Lymphatics are often overlooked as they are small slit-like structures above the hair follicle that resemble artifact-like separation of collagen bundles with some fixatives. Lymphatics are easily detected using lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) by immunohistochemistry to label their endothelial cells. Using LYVE1, there were no changes in distribution or numbers of lymphatics although they were more prominent (dilated) in the mice with AA. Lyve1 transcripts were not significantly upregulated except at 10 weeks after skin grafting when clinical signs of AA first become apparent. Other genes involved with vascular growth and dilation or movement of immune cells were dysregulated, mostly upregulated. These findings emphasize aspects of AA not commonly considered and provide potential targets for therapeutic intervention. PMID:26960166

  19. Acquired microcystic lymphatic malformation of the distal upper extremity mimicking verrucae vulgaris.

    Science.gov (United States)

    Wang, Stephanie; Krulig, Eliana; Hernandez, Claudia

    2013-01-01

    An 18-year-old African American male with a history of congenital lymphedema of the right upper extremity presented for evaluation of multiple verrucous lesions on his right hand. Clusters of 2 to 4-mm dome-shaped vesicles were intermixed with scattered verrucous papules on the right forearm and the dorsal and palmar aspects of the hand. Histopathology of one the verrucous lesions showed well-circumscribed areas of dilated lymphatic vascular channels with lymph in the lumen. The patient was diagnosed with microcystic lymphatic malformation, verrucous type. This article reviews the literature regarding reports of this variant of microcystic lymphatic malformation in the pediatric population. © 2013 Wiley Periodicals, Inc.

  20. Visualisation of blood and lymphatic vessels with increasing exposure time of the detector

    Science.gov (United States)

    Kalchenko, V. V.; Kuznetsov, Yu L.; Meglinski, I. V.

    2013-07-01

    We describe the laser speckle contrast method for simultaneous noninvasive imaging of blood and lymphatic vessels of living organisms, based on increasing detector exposure time. In contrast to standard methods of fluorescent angiography, this technique of vascular bed imaging and lymphatic and blood vessel demarcation does not employ toxic fluorescent markers. The method is particularly promising with respect to the physiology of the cardiovascular system under in vivo conditions.

  1. Preferential lymphatic growth in bronchus-associated lymphoid tissue in sustained lung inflammation.

    Science.gov (United States)

    Baluk, Peter; Adams, Alicia; Phillips, Keeley; Feng, Jennifer; Hong, Young-Kwon; Brown, Mary B; McDonald, Donald M

    2014-05-01

    Lymphatics proliferate, become enlarged, or regress in multiple inflammatory lung diseases in humans. Lymphatic growth and remodeling is known to occur in the mouse trachea in sustained inflammation, but whether intrapulmonary lymphatics exhibit similar plasticity is unknown. We examined the time course, distribution, and dependence on vascular endothelial growth factor receptor (VEGFR)-2/VEGFR-3 signaling of lung lymphatics in sustained inflammation. Lymphatics in mouse lungs were examined under baseline conditions and 3 to 28 days after Mycoplasma pulmonis infection, using prospero heomeobox 1-enhanced green fluorescence protein and VEGFR-3 as markers. Sprouting lymphangiogenesis was evident at 7 days. Lymphatic growth was restricted to regions of bronchus-associated lymphoid tissue (BALT), where VEGF-C-producing cells were scattered in T-cell zones. Expansion of lung lymphatics after infection was reduced 68% by blocking VEGFR-2, 83% by blocking VEGFR-3, and 99% by blocking both receptors. Inhibition of VEGFR-2/VEGFR-3 did not prevent the formation of BALT. Treatment of established infection with oxytetracycline caused BALT, but not the lymphatics, to regress. We conclude that robust lymphangiogenesis occurs in mouse lungs after M. pulmonis infection through a mechanism involving signaling of both VEGFR-2 and VEGFR-3. Expansion of the lymphatic network is restricted to regions of BALT, but lymphatics do not regress when BALT regresses after antibiotic treatment. The lung lymphatic network can thus expand in sustained inflammation, but the expansion is not as reversible as the accompanying inflammation. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. 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

    2017-10-01

    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 its 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 the low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate the requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels, and suggest an ECM-controlled checkpoint that prevents SMC investment of capillaries, which is a common feature in lymphedematous skin. © 2017. Published by The Company of Biologists Ltd.

  3. 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

    2017-01-01

    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 its 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 the low presence of PDGFB-binding ECM components around lymphatic capillaries. These results demonstrate the requirement of LEC-autonomous PDGFB expression and retention for SMC recruitment to lymphatic vessels, and suggest an ECM-controlled checkpoint that prevents SMC investment of capillaries, which is a common feature in lymphedematous skin. PMID:28851707

  4. Lymphatic malformation is a common component of Klippel-Trenaunay syndrome.

    Science.gov (United States)

    Liu, Ning-Fei; Lu, Qing; Yan, Zhi-Xin

    2010-12-01

    Few previous studies have focused on the involvement of the lymphatic system in Klippel-Trenaunay syndrome (KTS), although some evidence suggests that lymphatic abnormalities are associated with the disease. The aim of the present study was to investigate the involvement of the lymphatic system in KTS. Magnetic resonance lymphangiography (MRL) with the use of gadobenate dimeglumine as the contrast was performed on 32 patients with KTS involving the extremities to evaluate lymphatic vessels, lymph nodes, and veins. Thirty-one of 32 patients exhibited lymphatic vessel and/or lymph node anomalies, including hyperplasia (11/31), hypoplasia or aplasia (20/31) of lymphatic vessels, and lymphedema (31/31) of the affected limbs. Twenty-two patients showed asymmetry of the inguinal nodes exhibiting either the absence, or an increase or a decrease in number and size of the inguinal nodes. Venous dysplasia was found in 31 patients in superficial and/or deep veins. The results showed a high concomitance of malformations of the lymphatic system and veins in the affected limbs of patients with KTS. Lymphatic system abnormalities as examined with MRL are commonly associated with KTS and are likely to play a significant role in the disorder. Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  5. Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

    Science.gov (United States)

    Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

    2017-01-01

    Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

  6. Core content for training in venous and lymphatic medicine.

    Science.gov (United States)

    Zimmet, Steven E; Min, Robert J; Comerota, Anthony J; Meissner, Mark H; Carman, Teresa L; Rathbun, Suman W; Jaff, Michael R; Wakefield, Thomas W; Feied, Craig F

    2014-10-01

    The major venous societies in the United States share a common mission to improve the standards of medical practitioners, the educational goals for teaching and training programs in venous disease, and the quality of patient care related to the treatment of venous disorders. With these important goals in mind, a task force made up of experts from the specialties of dermatology, interventional radiology, phlebology, vascular medicine, and vascular surgery was formed to develop a consensus document describing the Core Content for venous and lymphatic medicine and to develop a core educational content outline for training. This outline describes the areas of knowledge considered essential for practice in the field, which encompasses the study, diagnosis, and treatment of patients with acute and chronic venous and lymphatic disorders. The American Venous Forum and the American College of Phlebology have endorsed the Core Content. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. LYMPHATIC VESSELS IN HEALTH AND DISEASE

    Science.gov (United States)

    Kesler, Cristina T.; Liao, Shan; Munn, Lance L.; Padera, Timothy P.

    2012-01-01

    The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism and cancer metastasis. In adults, lymphatic vessel formation and remodeling occurs primarily during inflammation, development of the corpus luteum, wound healing, and tumor growth. Unlike the blood circulation, where unidirectional flow is sustained by the pumping actions of the heart, pumping actions intrinsic to the lymphatic vessels themselves are important drivers of lymphatic flow. This review summarizes critical components that control lymphatic physiology. PMID:23209022

  8. Urban lymphatic filariasis

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Mwakitalu, Mbutolwe E.

    2013-01-01

    Lymphatic filariasis (LF) is a disabling and disfiguring disease resulting from a mosquito-borne parasitic infection. It is a major public health problem in many countries with a warm climate. Research and control activities have mainly focused on LF in rural areas where it also has its major...... 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...... 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...

  9. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

    Science.gov (United States)

    The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

  10. Immunology of lymphatic filariasis.

    Science.gov (United States)

    Babu, S; Nutman, T B

    2014-08-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen-specific Th2 response and an expansion of IL-10 producing CD4(+) T cells that is accompanied by a muted Th1 response. This antigen-specific T-cell hyporesponsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4(+) T-cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T-cell hyporesponsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  11. Erythropoietin attenuates pulmonary vascular remodeling in experimental pulmonary arterial hypertension through interplay between endothelial progenitor cells and heme-oxygenase

    Directory of Open Access Journals (Sweden)

    Rosa L.E. Loon

    2015-08-01

    Full Text Available BackgroundPulmonary arterial hypertension (PAH is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs and activation of the cytoprotective enzyme heme oxygenase-1 (HO1.MethodsRats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity-inhibitor tin-mesoporphyrin (SnMP. HO-activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks.ResultsIn PAH-rats, circulating EPCs were decreased and HO-activity was increased compared to control. EPO-treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO-activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone.ConclusionsIn experimental PAH, EPO treatment restored the number of circulating EPC’s to control level, improved pulmonary vascular remodeling, and showed important interplay with HO-activity. Inhibition of increased HO-activity in PAH-rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored numbers of circulating EPC’s. We suggest that both EPO-induced HO1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH.

  12. Presence of lymphatics in a rat tendon lesion model.

    Science.gov (United States)

    Tempfer, Herbert; Kaser-Eichberger, Alexandra; Korntner, Stefanie; Lehner, Christine; Kunkel, Nadja; Traweger, Andreas; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Bruckner, Daniela; Krefft, Karolina; Heindl, Ludwig M; Reitsamer, Herbert A; Schrödl, Falk

    2015-04-01

    Tendons lack sufficient blood supply and represent a bradytroph tissue with prolonged healing time under pathological conditions. While the role of lymphatics in wound/defect healing in tissues with regular blood supply is well investigated, its involvement in tendon defects is not clear. We here try to identify the role of the lymphatic system in a tendon lesion model with morphological methods. A rat Achilles tendon lesion model (n = 5) was created via surgical intervention. Two weeks after surgery, animals were killed and lesioned site removed and prepared for polarization microscopy (picrosirius red) and immunohistochemistry using the lymphatic markers PROX1, VEGFR3, CCL21, LYVE-1, PDPN, and the vascular marker CD31. Additionally, DAPI was applied. Untreated tendons served as controls, confocal laser-scanning microscopy was used for documentation. At the lesion site, polarization microscopy revealed a structural reintegration while immunohistochemistry detected band-like profiles immunoreactive for PDPN, VEGFR3, CCL21, LYVE1, and CD31, surrounding DAPI-positive nuclei. PROX1-positive nuclei were detected within the lesion forming lines and opposed to each other. These PROX1-positive nuclei were surrounded by LYVE-1- or VEGFR3-positive surfaces. Few CD31-positive profiles contained PROX1-positive nuclei, while the majority of CD31-positive profiles lacked PROX1-positive nuclei. VEGFR3-, PDPN-, and LYVE-1-positive profiles were numerous within the lesion site, but absent in control tissue. Within 2 weeks, a structural rearrangement takes place in this lesion model, with dense lymphatic supply. The role of lymphatics in tendon wound healing is unclear, and proposed model represents a good possibility to study healing dynamics and lymphangiogenesis in a tissue almost completely lacking lymphatics in physiological conditions.

  13. Heterogeneous characteristics of lymphatic microvasculatures associated with pulmonary sarcoid granulomas.

    Science.gov (United States)

    Yamashita, Masahiro; Mouri, Takashi; Niisato, Miyuki; Kowada, Kouko; Kobayashi, Hitoshi; Chiba, Ryoji; Satoh, Takashi; Sugai, Tamotsu; Sawai, Takashi; Takahashi, Tohru; Yamauchi, Kohei

    2013-04-01

    Pulmonary sarcoidosis is a disorder characterized by noncaseating epithelioid granulomas that are anatomically distributed along lymphogenous routes. Currently, limited information is available about lymphangiogenesis in pulmonary sarcoidosis. To clarify the characteristics of lymphangiogenesis in pulmonary sarcoidosis. The concentrations of vascular endothelial growth factor (VEGF), VEGF-C, and VEGF-D in serum and bronchoalveolar lavage fluid from 65 patients with pulmonary sarcoidosis, 10 with idiopathic pulmonary fibrosis, and 29 healthy volunteers were measured by ELISA. Paraffin-embedded lung tissues obtained from 19 patients were used for immunohistochemical analyses, using primary antibodies against VEGF, VEGF-C, VEGF-D, podoplanin, VEGF receptor (VEGFR)-2, VEGFR-3, and CD73. The serum and bronchoalveolar lavage fluid concentrations of VEGF and VEGF-C were significantly increased in patients with pulmonary sarcoidosis. Immunohistochemical analysis showed that VEGF and VEGF-C were expressed in sarcoid granulomas. Immunostaining with anti-podoplanin antibody for the detection of lymphatic vasculatures showed the presence of usual lymphatics and atypical tubular structures around sarcoid granulomas. Atypical tubular structures were characterized by a thin membrane, with weak expression of podoplanin and a membrane deficit in a part of the borderline. The structures were observed in around 58.6% of the total of 193 granulomas, whereas usual lymphatics were limited in 15.6%. Atypical tubular structures were coexpressed with VEGFR-2, but not VEGFR-3, whereas VEGFR-3 was expressed in usual lymphatics. Part of the tubular structures was connected to CD73(+) afferent lymphatics. These results indicate the presence and the importance of heterogeneous lymphatic microvasculature around sarcoid granulomas in pulmonary sarcoidosis.

  14. 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...... with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania....

  15. Effects of allicin on hyperhomocysteinemia-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Liu, De-shan; Gao, Wei; Liang, Er-shun; Wang, Shu-li; Lin, Wei-wei; Zhang, Wei-dong; Jia, Qing; Guo, Rui-chen; Zhang, Ji-dong

    2013-08-15

    This study was designed to investigate the effect and mechanism of allicin on hyperhomocysteinemia-induced experimental vascular endothelial dysfunction in rats. Fifty male Wistar rats were randomly divided into five groups: the normal control rats (NC), the high-methionine-diet rats (Met), the high-methionine-diet rats treated with folic acid, vitaminB₆ and vitaminB₁₂ (Met+F), or with low-dose allicin (Met+L), or with high-dose allicin (Met+H). After 6 weeks, we collected blood samples of all groups to determine plasma endothelin (ET), serum homocysteine (Hcy), nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and detected the expression of basic fibroblast growth factors (bFGF), transforming growth factor beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in the aorta. The Hcy and the expression of TGF-β in both the Met+L and Met+H groups were significantly lower than the Met and Met+F groups. The ET, ET/NO ratio and the MDA levels of the Met+L and Met+H groups were significantly lower than the Met group. The SOD and NO levels and the expression of bFGF, TNF-α and ICAM-1 of the Met+L and Met+H groups were significantly higher than the Met group. Our data indicate that allicin inhibits lipid peroxidation induced by hyperhomocysteinemia and regulates the excretion and equilibrium of ET and NO, and suggest that allicin might be useful in the prevention of endothelial dysfunction caused by hyperhomocysteinemia. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Treprostinil in advanced experimental pulmonary hypertension : Beneficial outcome without reversed pulmonary vascular remodeling

    NARCIS (Netherlands)

    van Albada, Mirjam E.; van Veghel, Richard; Cromme-Dijkhuis, Adri H.; Schoemaker, Regien G.; Berger, Ro F. M. E.

    2006-01-01

    Introduction: Beneficial effects of treprostmil, a stable prostacyclin analogue, were demonstrated in patients with pulmonary arterial hypertension (PAH). Although regression of pulmonary vascular remodeling has been suggested as therapeutic mechanism, its mode of action remains unknown. Methods:

  17. 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.

  18. Mastering Lymphatic Microsurgery: A New Training Model in Living Tissue.

    Science.gov (United States)

    Campisi, Corrado Cesare; Jiga, Lucian P; Ryan, Melissa; di Summa, Pietro G; Campisi, Corradino; Ionac, Mihai

    2017-09-01

    Advanced microsurgical techniques have emerged as a promising approach for the treatment of lymphedema, but achieving international standards is limited by a scarcity of adequate training models. The purpose of this report is to describe our in vivo porcine training model for microsurgery. Five female common-breed pigs (Sus scrofa domesticus) weighing 20 to 28 kg were placed under general anesthesia, and blue patent violet dye was injected to highlight lymphatic structures and prepare the pigs for anatomical exploration and microsurgery. The number and type of patent anastomoses achieved and lymph node flaps created and any anatomical differences between porcine and human vessels were noted, in light of evaluating the use of pigs as a training model for microsurgery in living tissue. Multiple lymphatic-venous anastomoses were created at the site of a single incision made at the subinguinal region, running medial and parallel to the saphenous vessels. Ten multiple lymphatic-venous anastomoses were created in total, and all were demonstrated to be patent. Four lymph node flaps were prepared for lymph node transfer. The superficial lymphatic collector system in the caudal limb of the pig was identified and described with particular reference to the superficial, medial (dominant), and lateral branches along the saphenous vein and its accessory. The authors present a safe and adaptable in vivo experimental microsurgical porcine model that provides the opportunity to practice several advanced lymphatic microsurgical techniques in the same animal. The ideal lymph node transfer training model can be developed from this anatomical detail, giving the opportunity to use it for artery-to-artery anastomoses, vein-to-vein anastomoses, and lymphatic-to-lymphatic anastomoses.

  19. Lymphatic Stomata in the Adult Human Pulmonary Ligament.

    Science.gov (United States)

    Oshiro, Hisashi; Miura, Masahiro; Iobe, Hiroaki; Kudo, Tomoo; Shimazu, Yoshihito; Aoba, Takaaki; Okudela, Koji; Nagahama, Kiyotaka; Sakamaki, Kentaro; Yoshida, Maki; Nagao, Toshitaka; Nakaya, Takeo; Kurata, Atsushi; Ohtani, Osamu

    2015-06-01

    Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata. A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 μm in the left pulmonary ligaments and from 2.50 to 12.50 μm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm(2) in the left pulmonary ligaments and from 2 to 18 per mm(2) in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments. Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura.

  20. Essential Role of the Coxsackie - and Adenovirus Receptor (CAR) in Development of the Lymphatic System in Mice

    Science.gov (United States)

    Zaini, Mohamad Amr; Haiko, Paula; Tammela, Tuomas; Alitalo, Kari; Philipson, Lennart; Fuxe, Jonas; Sollerbrant, Kerstin

    2012-01-01

    The coxsackie- and adenovirus receptor (CAR) is a cell adhesion molecule predominantly associated with epithelial tight junctions in adult tissues. CAR is also expressed in cardiomyocytes and essential for heart development up to embryonic day 11.5, but not thereafter. CAR is not expressed in vascular endothelial cells but was recently detected in neonatal lymphatic vessels, suggesting that CAR could play a role in the development of the lymphatic system. To address this, we generated mice carrying a conditional deletion of the CAR gene (Cxadr) and knocked out CAR in the mouse embryo at different time points during post-cardiac development. Deletion of Cxadr from E12.5, but not from E13.5, resulted in subcutaneous edema, hemorrhage and embryonic death. Subcutaneous lymphatic vessels were dilated and structurally abnormal with gaps and holes present at lymphatic endothelial cell-cell junctions. Furthermore, lymphatic vessels were filled with erythrocytes showing a defect in the separation between the blood and lymphatic systems. Regionally, erythrocytes leaked out into the interstitium from leaky lymphatic vessels explaining the hemorrhage detected in CAR-deficient mouse embryos. The results show that CAR plays an essential role in development of the lymphatic vasculature in the mouse embryo by promoting appropriate formation of lymphatic endothelial cell-cell junctions. PMID:22624044

  1. The chemokine receptors ACKR2 and CCR2 reciprocally regulate lymphatic vessel density

    Science.gov (United States)

    Lee, Kit M; Danuser, Renzo; Stein, Jens V; Graham, Delyth; Nibbs, Robert JB; Graham, Gerard J

    2014-01-01

    Macrophages regulate lymphatic vasculature development; however, the molecular mechanisms regulating their recruitment to developing, and adult, lymphatic vascular sites are not known. Here, we report that resting mice deficient for the inflammatory chemokine-scavenging receptor, ACKR2, display increased lymphatic vessel density in a range of tissues under resting and regenerating conditions. This appears not to alter dendritic cell migration to draining lymph nodes but is associated with enhanced fluid drainage from peripheral tissues and thus with a hypotensive phenotype. Examination of embryonic skin revealed that this lymphatic vessel density phenotype is developmentally established. Further studies indicated that macrophages and the inflammatory CC-chemokine CCL2, which is scavenged by ACKR2, are associated with this phenotype. Accordingly, mice deficient for the CCL2 signalling receptor, CCR2, displayed a reciprocal phenotype of reduced lymphatic vessel density. Further examination revealed that proximity of pro-lymphangiogenic macrophages to developing lymphatic vessel surfaces is increased in ACKR2-deficient mice and reduced in CCR2-deficient mice. Therefore, these receptors regulate vessel density by reciprocally modulating pro-lymphangiogenic macrophage recruitment, and proximity, to developing, resting and regenerating lymphatic vessels. PMID:25271254

  2. The chemokine receptors ACKR2 and CCR2 reciprocally regulate lymphatic vessel density.

    Science.gov (United States)

    Lee, Kit M; Danuser, Renzo; Stein, Jens V; Graham, Delyth; Nibbs, Robert J B; Graham, Gerard J

    2014-11-03

    Macrophages regulate lymphatic vasculature development; however, the molecular mechanisms regulating their recruitment to developing, and adult, lymphatic vascular sites are not known. Here, we report that resting mice deficient for the inflammatory chemokine-scavenging receptor, ACKR2, display increased lymphatic vessel density in a range of tissues under resting and regenerating conditions. This appears not to alter dendritic cell migration to draining lymph nodes but is associated with enhanced fluid drainage from peripheral tissues and thus with a hypotensive phenotype. Examination of embryonic skin revealed that this lymphatic vessel density phenotype is developmentally established. Further studies indicated that macrophages and the inflammatory CC-chemokine CCL2, which is scavenged by ACKR2, are associated with this phenotype. Accordingly, mice deficient for the CCL2 signalling receptor, CCR2, displayed a reciprocal phenotype of reduced lymphatic vessel density. Further examination revealed that proximity of pro-lymphangiogenic macrophages to developing lymphatic vessel surfaces is increased in ACKR2-deficient mice and reduced in CCR2-deficient mice. Therefore, these receptors regulate vessel density by reciprocally modulating pro-lymphangiogenic macrophage recruitment, and proximity, to developing, resting and regenerating lymphatic vessels. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  3. Mechanisms of lymphatic regeneration after tissue transfer.

    Directory of Open Access Journals (Sweden)

    Alan Yan

    2011-02-01

    Full Text Available 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.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.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.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 and promote rapid lymphatic regeneration.

  4. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Absence of lymphatic vessels in the dog dental pulp: an immunohistochemical study.

    Science.gov (United States)

    Martin, Anna; Gasse, Hagen; Staszyk, Carsten

    2010-11-01

    In spite of numerous investigations it has not been precisely determined whether lymphatic vessels are present in the dental pulp of dogs. Therefore, this study attempted a specific immunohistochemical detection of lymphatic endothelium. The canine teeth of 19 healthy beagle dogs were dissected into three segments (apical, intermediate and occlusal). After decalcification, specimens were embedded in paraffin wax and histologic cross-sections were stained immunohistochemically using a reliable antibody (anti-Prox-1) against the homeobox transcription factor Prox-1, which is located within the nucleus of lymphatic endothelium. Anti-Prox-1 reacted positively with canine control tissues (lymph nodes, gingiva, nasal mucosa), but showed no staining in tissue sections of the dental pulp. The dog dental pulp contained no vascular structures lined with lymphatic endothelium. This suggests that drainage of interstitial fluid makes use of other routes, i.e. extravascular pathways. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.

  6. A reproducible in-vivo model of lymphatic malformation in rats.

    Science.gov (United States)

    Sun, Y; Jia, J; Zhang, W; Liu, B; Zhang, Z; Zhao, Y

    2011-11-01

    The aim of this study was to develop a reproducible rat model of lymphatic malformation. Different types of adjuvant, with and without vascular endothelial growth factor (VEGF)-C, was injected into the neck and floor of the mouth of rats. The rats were killed 2 months after the injection. Injected rats developed cystic lesions in the neck and floor of the mouth. Immunohistochemical examination revealed that the cysts were lined by endothelium, which expressed the lymphatic endothelial markers LYVE-1 and VEGF receptor-3. Raman spectra of the liquid contents of the cysts were similar in all injected rats. Transmission electron microscopy revealed that the endothelial cells had no basement membrane or surrounding pericytes. The cystic lesions were consistent with human lymphatic malformation. This animal model could be used to investigate pathogenesis of lymphatic malformation and its responses to candidate therapies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Extensive Fetal Congenital Subcutaneous Mixed Venous Lymphatic Lesion: Prenatal Diagnosis and Postnatal Management

    Directory of Open Access Journals (Sweden)

    I. N. Odibo

    2015-04-01

    Full Text Available Vascular lesions may be categorized as proliferative tumors, such as hemangiomas, or nonproliferative malformations that include capillary, lymphatic, venous, arterial, or mixed lesions. Lymphatic malformations are benign localized congenital malformations of the lymphatic system. They may be microcystic or macrocystic lesions or a combination of both. The lesions may also be uniseptate or multiseptate, and are more commonly located in the head and neck or axillary region. Prenatal diagnosis is based on ultrasound and magnetic resonance imaging. Postnatal management largely depends on the size and location of the lesion. This is the first case report of prenatally diagnosed extensive subcutaneous macrocystic venous lymphatic malformation involving the fetal thorax, back, pelvis, and lower extremities. Prenatal course and postnatal management are described. This report will aid other specialists in the field of prenatal diagnosis and postnatal surgery in the evaluation and management of these patients.

  8. Radiological analysis of disorder combined with lymphatic stasis: Part 1. Lymphatic stasis due to malignant metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, T. S.; Suh, J. S.; Lee, J. D.; Kim, G. E.; Park, C. Y.; Park, C. K. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1982-09-15

    The analysis of 35 cases who revealed lymphatic obstruction and lymphatic stasis due to malignant metastasis on bipedal lymphangiography, to evaluate the various radiological patterns of lymphatic obstruction and pathophysiologic mechanisms due to lymphatic obstruction, from Oct. 1975 to Apr. 1982 at YUMC Hospital was undertaken and the following results were obtained. 1. Of these, 12 had complete lymphatic obstruction and 22 partial lymphatic obstruction on lymphangiography. There was lymphatic collateral circulation in 14, extravasation of contrast media in 12, lymphatic dilatation in 9, dermal backflow in 6, and only lymphatic stasis in 10. 2. According to the level or location of lymphatic obstruction, there were 17 at external iliac lymph nodes, 10 below the inguinal lymph nodes, and 8 above the common iliac lymph nodes. 3. Lymphatic collateral circulation was developed mainly by neoformation of subcutaneous lymphatics below the inguinal lymph nodes obstruction, collateral flow into the internal iliac lymphatics at external iliac lymph nodes obstruction, collateral flow into the mesenteric and mediastinal lymphatics above the common iliac lymph nodes obstruction. 4. Pulmonary oil embolism was developed in 12 of 175 (7%) in control group, but in 14 of 35 (40%) in lymphatic obstruction group. Finally, the dynamic evaluation of lymphatic flow on lymphangiography is more important than the morphologic evaluation of lymph nodes in advanced malignant disease.

  9. Immunohistochemical investigation of lymphatic vessel formation control in mouse tooth development: lymphatic vessel-forming factors and receptors in tooth development in mice.

    Science.gov (United States)

    Takahashi, S; Ambe, K; Kon, H; Takada, S; Ohno, T; Watanabe, H

    2012-06-01

    The presence of lymphatic vessels in dental pulp has recently been controversial, and no conclusion has been reached. In this study, we investigated the control of lymphangiogenesis with dental pulp development in the mouse mandibular molar using VEGF-C, VEGF-D, and VEGFR-3 as indices of lymphatic vessel-controlling factors. In addition, to distinguish blood and lymphatic vascular epithelial cells, we performed immunohistochemical analysis using von Willebrand factor (vWF) and statistical analysis. In dental papilla in the bell-stage non-calcified period, mesenchymal cells positive for VEGF-C, VEGF-D, and VEGFR-3 increased and lumen-forming endothelial cells were noted, but vWF was negative, suggesting that these were actively forming lymphatic vessels. Positive undifferentiated mesenchymal cells, an increase in endothelial cells in dental pulp, and lumen expansion were noted early after birth. Positivity was also detected in the odontoblast layer and sheath of Hertwig after birth, suggesting that these factors also play important roles in odontoblast differentiation and maturation and periodontal ligament and tooth root formation. We embryologically clarified lymphatic vessel formation in dental pulp and a process of lymphatic vessel formation from blood vessels, suggesting involvement of the surrounding tissue, odontoblasts, and sheath of Hertwig in vessel formation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Fluid-solid modeling of lymphatic valves

    Science.gov (United States)

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

    2015-11-01

    The lymphatic system performs important physiological functions such as the return of interstitial fluid to the bloodstream to maintain tissue fluid balance, as well as the transport of immune cells in the body. It utilizes contractile lymphatic vessels, which contain valves that open and close to allow flow in only one direction, to directionally pump lymph against a pressure gradient. We develop a fluid-solid model of geometrically representative lymphatic valves. Our model uses a hybrid lattice-Boltzmann lattice spring method to capture fluid-solid interactions with two-way coupling between a viscous fluid and lymphatic valves in a lymphatic vessel. We use this model to investigate the opening and closing of lymphatic valves, and its effect on lymphatic pumping. This helps to broaden our understanding of the fluid dynamics of the lymphatic system.

  11. Acupuncture ameliorates cognitive impairment and hippocampus neuronal loss in experimental vascular dementia through Nrf2-mediated antioxidant response.

    Science.gov (United States)

    Wang, Xue-Rui; Shi, Guang-Xia; Yang, Jing-Wen; Yan, Chao-Qun; Lin, Li-Ting; Du, Si-Qi; Zhu, Wen; He, Tian; Zeng, Xiang-Hong; Xu, Qian; Liu, Cun-Zhi

    2015-12-01

    Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over-activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation. Copyright © 2015. Published by Elsevier Inc.

  12. 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.)

  13. Surgical anatomy of gastric lymphatic drainage

    OpenAIRE

    Lirosi, Maria Carmen; Biondi, Alberto; Ricci, Riccardo

    2017-01-01

    The lymphatic system of the stomach is a multidirectional and complex network composed of lymphatic nodes and vessels. Lymph node metastasis is the most important prognostic factor in curable gastric cancer and lymph node dissection is one of the main areas of surgical research in gastric cancer. Therefore the anatomical classification and embryological development of the gastric lymphatic system have been well described in the literature. The current description of the gastric lymphatic syst...

  14. Interplay between Inflammatory Responses and Lymphatic Vessels.

    Science.gov (United States)

    Shin, Kihyuk; Lee, Seung-Hyo

    2014-08-01

    Lymphatic vessels are routes for leukocyte migration and fluid drainage. In addition to their passive roles in migration of leukocytes, increasing evidence indicates their active roles in immune regulation. Tissue inflammation rapidly induces lymphatic endothelial cell proliferation and chemokine production, thereby resulting in lymphangiogenesis. Furthermore, lymphatic endothelial cells induce T cell tolerance through various mechanisms. In this review, we focus on the current knowledge on how inflammatory cytokines affect lymphangiogenesis and the roles of lymphatic vessels in modulating immune responses.

  15. Acute neonatal presentation of a lymphatic malformation

    OpenAIRE

    Tang, Chee Yan; Van Wijnen, M; van Sambeeck, S J; Halbertsma, F J J

    2013-01-01

    Oropharyngeal lymphatic malformations usually present with a mass either at birth or in the first 2 years of life. Rarely, lymphatic malformations present with extremely progressive respiratory problems shortly after birth, and usually occur in cases which have remained undetected in the absence of antenatal ultrasound. We report the case of a newborn that required tracheostomy and gastrostomy due to a rapidly expansive lymphatic malformation. MRI showed multilocular microcystic lymphatic mal...

  16. Experimental study of sutureless vascular anastomosis with use of glued prosthesis in rabbits.

    Science.gov (United States)

    Vokrri, Lulzim; Qavdarbasha, Arsim; Rudari, Hajriz; Ahmetaj, Halil; Manxhuka-Kërliu, Suzana; Hyseni, Nexhmi; Porcu, Paolo; Cinquin, Philippe; Sessa, Carmine

    2015-01-01

    The objective of this study is to explore the feasibility and efficacy of a new technique for sutureless vascular anastomosis, using glued prosthesis, as a sole anastomosis fixation method in rabbits. Ten rabbits were randomly selected to conduct the experiment. Five rabbits underwent direct anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other rabbits, reconstruction was done by sutured anastomosis. All animals were immediately examined by echo-Doppler for patency of anastomosis. The burst pressure of the glued anastomosis was measured and compared with that of a sutured artery. The animals were euthanized, and tissue samples were taken for histological examination immediately after the experiment. Compared to conventional anastomoses, sutureless vascular anastomoses required shorter time of creation and significantly reduced blood loss (Pprosthesis, examined by echo-Doppler, were patent at the anastomotic site, except one, which was stenosed immediately after surgery. In the control group, except one with stenosis, all conventional anastomoses were patent. Mean burst pressure at the anastomotic site for sutureless anastomoses was lower than in control group. Macroscopically, the BioGlue did not demonstrate any adhesion to the surrounding tissue as it was covered by the vascular prosthesis. Histological examination showed low-grade inflammatory reaction in glued anastomoses versus no inflammatory reaction at the sutured anastomoses. This technique may provide a feasible and successful alternative in vascular surgery. However, further long-term studies are necessary to elucidate the break pressure and degree of inflammation at the anastomotic site.

  17. Antiangiogenic activity of vitexicarpine in experimentally induced hepatocellular carcinoma: Impact on vascular endothelial growth factor pathway.

    Science.gov (United States)

    Hassoun, Shimaa M; Abdel-Rahman, Noha; Eladl, Entsar I; El-Shishtawy, Mamdouh M

    2017-06-01

    Angiogenesis plays important roles in progression of hepatocellular carcinoma. The antiangiogenic mechanisms of vitexicarpine are not fully defined. Therefore, we conducted the following study to evaluate the antiangiogenic mechanism and antitumor activity of vitexicarpine in vivo model of hepatocellular carcinoma through modulation of vascular endothelial growth factor signaling pathway. Hepatocellular carcinoma was induced in Sprague Dawley rats by thioacetamide. Hepatocellular carcinoma was assessed by measuring serum alpha-fetoprotein and investigating liver sections stained with hematoxylin/eosin. Hepatocellular carcinoma rats were injected with vitexicarpine (150 mg/kg) for 2 weeks. Hepatic vascular endothelial growth factor was measured by enzyme-linked immunosorbent assay. Protein and expression of hepatic phospho-Ser473-AKT (p-AKT) and phospho-Tyr419-Src (p-Src) were determined. The apoptotic pathway was evaluated by assessment of protein expression of caspase-3. Vitexicarpine increased rats' survival time and decreased serum alpha-fetoprotein as well as it ameliorated fibrosis and massive hepatic tissue breakdown. It attenuated hepatocellular carcinoma-induced protein and gene expression of vascular endothelial growth factor, p-AKT, p-Src, and caspase-3. In conclusion, this study suggests that vitexicarpine possesses both antiangiogenic and antitumor activities through inhibition of vascular endothelial growth factor, p-AKT/AKT, and p-Src with subsequent inhibition of apoptotic pathway.

  18. The Efficiency of Vascular Embolization Using Alginate Gel : An Experimental Study in Rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woo Baek; Kang, Yeong Han [Dept. of Diagnostic Radiology, Daegu Catholic University Hospital, Daegu (Korea, Republic of); Kim, Jong Ki [Dept. of Biomedical Engineering, Daegu Catholic University, Daegu (Korea, Republic of)

    2009-03-15

    The purpose of this study was to investigate the applicability of poly-L-guluronic alginate (PGA) gel in vascular embolization with angiography simulation. To prepare a gel-forming PGA from no guluronate-rich Laminaria japonica, a new acid hydrolysis method was employed with a lower HCL concentration (0.03 M) and a shorter treatment time (5 min). The obtained PGAs were selected based on gel stability and viscosity. Glass aneurysm model was used to simulate gel embolization in vitro. Then, finally, the PGA was used to embolize the renal vascular system by using a rabbit model and angiography. Glass aneurysm model was made to simulate gel embolization procedure. PGA solution was injected from pump through 2-way catheter. Subsequent injection of CaCl{sub 2} successfully formed gels inside aneurysm model that conforming to its inner contour. In rabbit model, first, renal artery and aorta leading to the right kidney were ligated to block blood flow, then conventional contrast agent was injected through aorta to check the arterial patency to the left kidney. In sequential artery injection method, PGA and CaCl{sub 2} were injected through renal artery sequentially via a single catheter. Re-injection of contrast agent after removing ligated aorta showed blood flow to the right kidney but no flow in the left kidney. This result demonstrated a complete blocking of blood flow due to gel formation in vascular bed of the left kidney. Instillation of calcium alginate into aneurysm model and arterial system in vivo produced an embolization that better fills and conforms to the contour of aneurysms or blocking vascular bed completely. Therefore, PGA was effective endovascular occlusion materials and provide an efficiency of vascular angiography.

  19. Lymphatic Malformation Architecture: Implications for Treatment With OK-432.

    Science.gov (United States)

    Malic, Claudia C; Guilfoyle, Regan; Courtemanche, Rebecca J M; Arneja, Jugpal S; Heran, Manraj K S; Courtemanche, Douglas J

    2017-10-01

    Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes. A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012. Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence. The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

  20. Rare lymphatic malformation in an extreme premature infant: answer

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    Veronica Mugarab Samedi

    2017-08-01

    Full Text Available We present a case of massive cystic lymph­angioma in an extreme preterm infant, which was initially diagnosed by prenatal ultrasound and confirmed by fetal MRI. Physical examination and postnatal ultrasound confirmed diagnosis of cystic lymphangioma. No other anomalies were detected, genetic screening for infant was normal. Despite of size of lymphatic malformation at birth, it was an isolated finding with minimal vascularity, thus the prognosis for self-resolution was very good. No surgical intervention was required other than skin care. The lesion started to decrease in size from day 5, and showed signs of gradual involution from the 2nd week of life.At 37 weeks of corrected gestational age lymphatic malformation underwent full resolution, with minimal pigmen­tation and scarring on the site of lesion.

  1. VEGFR-3 blocking deteriorates inflammation with impaired lymphatic function and different changes in lymphatic vessels in acute and chronic colitis.

    Science.gov (United States)

    Wang, Xiao-Lei; Zhao, Jing; Qin, Li; Cao, Jing-Li

    2016-01-01

    Recent studies show inflammation-associated lymphangiogenesis (IAL) induced by vascular endothelial growth factor receptor 3 (VEGFR-3) pathway has a close relationship with chronic intestinal inflammation, and antilymphatic signaling pathways may repress IAL. However, whether the biologic function of lymphatic vessel is the same in severe acute intestinal inflammation still remain unknown. C57BL/6 mice were administered with 5% of dextran sodium sulfate (DSS) in drinking water for 7 days to establish severe acute colitis (SAC) model. Chronic colitis (CC) model was established by three cycles of 2% DSS for 5 days following water for 5 days. Mice were treated with VEGFR-3 antibody once daily in SAC group, or once every 3 days in CC group. The colon inflammation, submucosal edema, lymphatic vessel (LV) density, LV size, lymph flow, cytokines and immune cells infiltration were detected. Both acute and chronic colitis resulted in a significant aggravation of colon inflammation in anti-VEGFR-3-treated mice, compared with PBS-treated colitis mice. Meanwhile, this was accompanied with decreased lymph drainage, increased submucosal edema, inflammatory cells infiltration and cytokines levels. In acute intestinal inflammation, significantly distorted and enlarged lymphatics were found but the LV number remained unchanged; not only significantly distorted and enlarged lymphatics but reduced LV number were found in chronic colitis. Blocking VEGFR-3 in acute and chronic colitis leads to deterioration of colon inflammation with impaired lymphatic function and different changes in LVs. In the therapy targeting VEGF-C/VEGFR-3 pathway for lymphangiogenesis, the phrase and severity of intestinal inflammation should be taken into account.

  2. Adipose derived stromal vascular fraction improves early tendon healing: an experimental study in rabbits

    Directory of Open Access Journals (Sweden)

    Mehdi Behfar

    2011-11-01

    Full Text Available Tendon never restores the complete biological and mechanical properties after healing. Bone marrow and recently adipose tissue have been used as the sources of mesenchymal stem cells, which have been proven to enhance tendon healing. Stromal vascular fraction (SVF, derived from adipose tissue by an enzymatic digestion, represents an alternative source of multipotent cells, which undergo differentiation into multiple lineages to be used in regenerative medicine. In the present study, we investigated potentials of this source on tendon healing. Twenty rabbits were divided into control and treatment groups. Five rabbits were used as donors of adipose tissue. The injury model was unilateral complete transection through the middle one third of deep digital flexor tendon. Immediately after suture repair, either fresh stromal vascular fraction from enzymatic digestion of adipose tissue or placebo was intratendinously injected into the suture site in treatments and controls, respectively. Cast immobilization was continued for two weeks after surgery. Animals were sacrificed at the third week and tendons underwent histological, immunohistochemical, and mechanical evaluations. By histology, improved fibrillar organization and remodeling of neotendon were observed in treatment group. Immunohistochemistry revealed an insignificant increase in collagen type III and I expression in treatments over controls. Mechanical testing showed significant increase in maximum load and energy absorption in SVF treated tendons. The present study showed that intratendinous injection of uncultured adipose derived stromal vascular fraction improved structural and mechanical properties of repaired tendon and it could be an effective modality for treating tendon laceration.

  3. A first vascularized skin equivalent as an alternative to animal experimentation.

    Science.gov (United States)

    Groeber, Florian; Engelhardt, Lisa; Lange, Julia; Kurdyn, Szymon; Schmid, Freia F; Rücker, Christoph; Mielke, Stephan; Walles, Heike; Hansmann, Jan

    2016-01-01

    Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.

  4. Immunopathogenesis of lymphatic filarial disease.

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    Babu, Subash; Nutman, Thomas B

    2012-11-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process-the first initiated by the parasite and host innate immune system and the second propagated mainly by the host's adaptive immune system and by other factors (including secondary infections).

  5. Functional imaging in tumor-associated lymphatics

    Science.gov (United States)

    Kwon, Sunkuk; Sevick-Muraca, Eva M.

    2011-03-01

    The lymphatic system plays an important role in cancer cell dissemination; however whether lymphatic drainage pathways and function change during tumor progression and metastasis remains to be elucidated. In this report, we employed a non-invasive, dynamic near-infrared (NIR) fluorescence imaging technique for functional lymphatic imaging. Indocyanine green (ICG) was intradermally injected into tumor-free mice and mice bearing C6/LacZ rat glioma tumors in the tail or hindlimb. Our imaging data showed abnormal lymphatic drainage pathways and reduction/loss of lymphatic contractile function in mice with lymph node (LN) metastasis, indicating that cancer metastasis to the draining LNs is accompanied by transient changes of the lymphatic architectural network and its function. Therefore, functional lymphatic imaging may provide a role in the clinical staging of cancer.

  6. Invasive lymphatic malformation (gorham-stout) of the pelvis with prominent skin involvement.

    Science.gov (United States)

    Leite, Inês; Hernández-Martín, Angela; Colmenero, Isabel; López-Gutiérrez, Juan C; Torrelo, Antonio

    2013-01-01

    Gorham-Stout syndrome is a rare disease characterized by progressive osteolysis leading to disappearance of the bone. Vascular proliferations have been implicated in the pathogenesis of this syndrome. The case of a 7-year-old girl with a prominent invasive lymphatic malformation on the lumbosacral area and massive osteolysis of the pelvic girdle is reported. © 2012 Wiley Periodicals, Inc.

  7. Magnetic Resonance Lymphangiography and Lymphatic Embolization in the Treatment of Pulmonary Complication of Lymphatic Malformation.

    Science.gov (United States)

    Itkin, Maxim

    2017-09-01

    Lymphatic malformations (LMs; especially those involving the central conducting lymphatic channels) are characterized by dysplastic and incompetent lymphatic channels in multiple tissues and organs. The major cause of mortality and morbidity in patients with thoracic LM is deterioration of pulmonary function due to chronic chylous effusions and progressive interstitial lung disease. The etiology of these pulmonary processes is unknown, although lymphatic involvement is certain. Understanding of the changes in the lymphatic anatomy in patients with LM has been hindered by difficulty of imaging of the lymphatic system. Recently developed dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) allows dynamic MR imaging of the lymphatic system by injecting gadolinium contrast agent in the groin lymph nodes. Using this technique, pathological lymphatic flow from the central lymphatic system and/or retroperitoneal and mediastinal masses into lung parenchyma ("pulmonary lymphatic perfusion syndrome") has been demonstrated in patients with LM. This abnormal lymphatic perfusion overflows pulmonary parenchyma and results in deterioration of pulmonary function due to interstitial process and/or compression effect of chylous effusions. Percutaneous thoracic duct embolization or lymphatic interstitial embolization of the lymphatic masses results in cessation of the pulmonary lymphatic overflow and significant improvement in pulmonary symptoms in these patients.

  8. Design principles for lymphatic drainage of fluid and solutes from collagen scaffolds.

    Science.gov (United States)

    Thompson, Rebecca L; Margolis, Emily A; Ryan, Tyler J; Coisman, Brent J; Price, Gavrielle M; Wong, Keith H K; Tien, Joe

    2018-01-01

    In vivo, tissues are drained of excess fluid and macromolecules by the lymphatic vascular system. How to engineer artificial lymphatics that can provide equivalent drainage in biomaterials remains an open question. This study elucidates design principles for engineered lymphatics, by comparing the rates of removal of fluid and solute through type I collagen gels that contain lymphatic vessels or unseeded channels, or through gels without channels. Surprisingly, no difference was found between the fluid drainage rates for gels that contained vessels or bare channels. Moreover, solute drainage rates were greater in collagen gels that contained lymphatic vessels than in those that had bare channels. The enhancement of solute drainage by lymphatic endothelium was more pronounced in longer scaffolds and with smaller solutes. Whole-scaffold imaging revealed that endothelialization aided in solute drainage by impeding solute reflux into the gel without hindering solute entry into the vessel lumen. These results were reproduced by computational models of drainage with a flow-dependent endothelial hydraulic conductivity. This study shows that endothelialization of bare channels does not impede the drainage of fluid from collagen gels and can increase the drainage of macromolecules by preventing solute transport back into the scaffold. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 106-114, 2018. © 2017 Wiley Periodicals, Inc.

  9. Absence of lymphatic vessels in human dental pulp: a morphological study.

    Science.gov (United States)

    Gerli, Renato; Secciani, Ilaria; Sozio, Francesca; Rossi, Antonella; Weber, Elisabetta; Lorenzini, Guido

    2010-04-01

    Few and controversial data are available in the literature regarding the presence of lymphatic vessels in the human dental pulp. The present study was designed to examine morphologically the existence of a lymph drainage system in human dental pulp. Human dental pulp and skin sections were immunohistochemically stained with specific antibodies for lymphatic endothelium (D2-40, LYVE-1, VEGFR-3 [vascular endothelial growth factor receptor-3], and Prox-1), with the pan-endothelial markers CD31 and von Willebrand factor (vWF), and with the blood-specific marker CD34. Several blood vessels were identified in human pulps and skin. Lymphatic vessels were found in all human skin samples but in none of the pulps examined. Western blotting performed on human dermis and on pulps treated with collagenase (to remove odontoblasts) confirmed these results. Transmission electron microscopy indicated that vessels which, by light microscopy, appeared to be initial lymphatic vessels had no anchoring filaments or discontinuous basement membrane, both of which are typical ultrastructural characteristics of lymphatic vessels. These results suggest that under normal conditions human dental pulp does not contain true lymphatic vessels. The various theories about dental pulp interstitial fluid circulation should be revised accordingly.

  10. Topical administration of Metamizole and its implications on vascular reactivity in Wistar rats- Experimental research

    Science.gov (United States)

    Coman, Ioana-Cristina; Paunescu, Horia; Stamate, Alina Cristina; Cherecheanu, Alina Popa; Ghita, Isabel; Barac, Cosmina; Vasile, Danut; Tudosescu, Ruxandra; Fulga, Ion

    2017-01-01

    Aim: The aim of this paper was to describe the possible implications of topical (ocular) administration of Metamizole on vascular reactivity of the iris in Wistar rats. No other study regarding its topical use was found. Methods: Male adult Wistar rats were anaesthetized with Ketamine 100 mg /kg body weight - injected intraperitoneally - while maintaining spontaneous respiration and the blink reflex. After selecting the area of interest (long posterior ciliary artery – LPCA), manual adjustments of the image magnitude, clarity, and brightness were made, and the experiment began. The image recording lasted 10 minutes. Results: Metamizole induced a slight vasoconstriction that started with the initial moment for all the doses used. After the topical administration of Metamizole, we did not observe an increase of the vascular diameter of LPCA in a dose dependent manner. The saline solution used as a negative control did not modify the vessel diameter. Conclusions: Metamizole (dipyrone) is a non-opioid drug, which is commonly used in human and veterinary medicine. It is the most popular first-line analgesic in various populations. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug. The high analgesic efficacy of metamizole, as well as its spasmolytic effect, makes it a very important pharmaceutical agent that could be used in the therapy of various eye disorders in humans and in animals. Abbreviations: COX = Cyclooxygenase; LPCA = Long Posterior Ciliary Artery; PRP = panretinal photocoagulation; PDR = proliferative diabetic retinopathy; Sec = second(s); VSPR = very severe non proliferative diabetic retinopathy

  11. Lymphangiogenesis and lymphatic function in periodontal disease.

    Science.gov (United States)

    Berggreen, E; Wiig, H

    2013-12-01

    Lymphatic vessels return extravasated fluid, proteins, and cells back into the circulation and are important in immune cell trafficking. In the gingiva, lymphatic vessels are located in the lamina propria and travel over the external surface of the alveolar bone. The gingival lymphatics are important for fluid drainage, since lack of lymphatics has been shown to increase interstitial fluid pressure and fluid volume. Maintenance of gingival lymphatic vessels requires continuous signaling by the growth factors VEGF-C and -D via their receptor VEGFR-3. The growth factors are expressed in the gingival epithelium and also in immune cells in the lamina propria. VEGF-C seems to be crucial for lymphangiogenesis induced during periodontal disease development. The lymphatic vessels protect against periodontitis in mice, probably by clearing bacteria and bacterial products and by promoting humoral immune responses. Down-regulation of CCL21, a ligand important for dendritic cell migration, has been demonstrated in lymphatics from patients with periodontitis. High enzymatic activity in the gingiva of these patients may also contribute to impaired lymphatic function, due to the loss of structural components in the interstitium influencing lymphatic function. So far, knowledge is limited in this field because of the dearth of studies on the role of lymphatic vessels in periodontal disease.

  12. C5a induces caspase-dependent apoptosis in brain vascular endothelial cells in experimental lupus.

    Science.gov (United States)

    Mahajan, Supriya D; Tutino, Vincent M; Redae, Yonas; Meng, Hui; Siddiqui, Adnan; Woodruff, Trent M; Jarvis, James N; Hennon, Teresa; Schwartz, Stanley; Quigg, Richard J; Alexander, Jessy J

    2016-08-01

    Blood-brain barrier (BBB) dysfunction complicates central nervous system lupus, an important aspect of systemic lupus erythematosus. To gain insight into the underlying mechanism, vascular corrosion casts of brain were generated from the lupus mouse model, MRL/lpr mice and the MRL/MpJ congenic controls. Scanning electron microscopy of the casts showed loss of vascular endothelial cells in lupus mice compared with controls. Immunostaining revealed a significant increase in caspase 3 expression in the brain vascular endothelial cells, which suggests that apoptosis could be an important mechanism causing cell loss, and thereby loss of BBB integrity. Complement activation occurs in lupus resulting in increased generation of circulating C5a, which caused the endothelial layer to become 'leaky'. In this study, we show that C5a and lupus serum induced apoptosis in cultured human brain microvascular endothelial cells (HBMVECs), whereas selective C5a receptor 1 (C5aR1) antagonist reduced apoptosis in these cells, demonstrating C5a/C5aR1-dependence. Gene expression of initiator caspases, caspase 1 and caspase 8, and pro-apoptotic proteins death-associated protein kinase 1, Fas-associated protein (FADD), cell death-inducing DNA fragmentation factor 45 000 MW subunit A-like effector B (CIDEB) and BCL2-associated X protein were increased in HBMVECs treated with lupus serum or C5a, indicating that both the intrinsic and extrinsic apoptotic pathways could be critical mediators of brain endothelial cell apoptosis in this setting. Overall, our findings suggest that C5a/C5aR1 signalling induces apoptosis through activation of FADD, caspase 8/3 and CIDEB in brain endothelial cells in lupus. Further elucidation of the underlying apoptotic mechanisms mediating the reduced endothelial cell number is important in establishing the potential therapeutic effectiveness of C5aR1 inhibition that could prevent and/or reduce BBB alterations and preserve the physiological function of BBB in

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

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    Hiroo Suami

    Full Text Available 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.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.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.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.

  14. Novel role of immature myeloid cells in formation of new lymphatic vessels associated with inflammation and tumors.

    Science.gov (United States)

    Ran, Sophia; Wilber, Andrew

    2017-08-01

    Inflammation triggers an immune cell-driven program committed to restoring homeostasis to injured tissue. Central to this process is vasculature restoration, which includes both blood and lymphatic networks. Generation of new vessels or remodeling of existing vessels are also important steps in metastasis-the major cause of death for cancer patients. Although roles of the lymphatic system in regulation of inflammation and cancer metastasis are firmly established, the mechanisms underlying the formation of new lymphatic vessels remain a subject of debate. Until recently, generation of new lymphatics in adults was thought to occur exclusively through sprouting of existing vessels without help from recruited progenitors. However, emerging findings from clinical and experimental studies show that lymphoendothelial progenitors, particularly those derived from immature myeloid cells, play an important role in this process. This review summarizes current evidence for the existence and significant roles of myeloid-derived lymphatic endothelial cell progenitors (M-LECPs) in generation of new lymphatics. We describe specific markers of M-LECPs and discuss their biologic behavior in culture and in vivo, as well as currently known molecular mechanisms of myeloid-lymphatic transition (MLT). We also discuss the implications of M-LECPs for promoting adaptive immunity, as well as cancer metastasis. We conclude that improved mechanistic understanding of M-LECP differentiation and its role in adult lymphangiogenesis may lead to new therapeutic approaches for correcting lymphatic insufficiency or excessive formation of lymphatic vessels in human disorders. © Society for Leukocyte Biology.

  15. The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine

    Science.gov (United States)

    Mahadevan, Aparna; Welsh, Ian C.; Sivakumar, Aravind; Gludish, David W.; Shilvock, Abigail R.; Noden, Drew M.; Kurpios, Natasza A.

    2015-01-01

    SUMMARY The dorsal mesentery (DM) is the major conduit for blood and lymphatic vessels in the gut. The mechanisms underlying their morphogenesis are challenging to study and remain unknown. Here we show that arteriogenesis in the DM begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12. Although competent Cxcr4-positive angioblasts are present on the right, they fail to form vessels and progressively emigrate. Surprisingly, gut lymphatics also initiate in the left DM and arise only after – and dependent on – arteriogenesis, implicating arteries as drivers of gut lymphangiogenesis. Our data begin to unravel the origin of two distinct vascular systems and demonstrate how early L-R molecular asymmetries are translated into organ-specific vascular patterns. We propose a dual origin of gut lymphangiogenesis, where prior arterial growth is required to initiate local lymphatics that only subsequently connect to the vascular system. PMID:25482882

  16. Effect of Oxysterol-Induced Apoptosis of Vascular Smooth Muscle Cells on Experimental Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Sonia Perales

    2009-01-01

    Full Text Available Smooth muscle cells (SMCs undergo changes related to proliferation and apoptosis in the physiological remodeling of vessels and in diseases such as atherosclerosis and restenosis. Recent studies also have demonstrated the vascular cell proliferation and programmed cell death contribute to changes in vascular architecture in normal development and in disease. The present study was designed to investigate the apoptotic pathways induced by 25-hydroxycholesterol in SMCs cultures, using an in vivo/in vitro cell model in which SMCs were isolated and culture from chicken exposed to an atherogenic cholesterol-rich diet (SMC-Ch and/or an antiatherogenic fish oil-rich diet (SMC-Ch-FO. Cells were exposed in vitro to 25-hydroxycholesterol to study levels of apoptosis and apoptotic proteins Bcl-2, Bcl-XL and Bax and the expression of bcl-2 and bcl-xL, genes. The quantitative real-time reverse transcriptase-polymerase chain reaction and the Immunoblotting western blot analysis showed that 25-hydroxycholesterol produces apoptosis in SMCs, mediated by a high increase in Bax protein and Bax gene expression. These changes were more marked in SMC-Ch than in SMC-Ch-FO, indicating that dietary cholesterol produces changes in SMCs that make them more susceptible to 25-hydroxycholesterol-mediated apoptosis. Our results suggest that the replacement of a cholesterol-rich diet with a fish oil-rich diet produces some reversal of cholesterol-induced changes in the apoptotic pathways induced by 25-hydroxycholesterol in SMCs cultures, making SMCs more resistant to apoptosis.

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Lymphatic drainage of the brain and the pathophysiology of neurological disease.

    Science.gov (United States)

    Weller, Roy O; Djuanda, Effie; Yow, Hong-Yeen; Carare, Roxana O

    2009-01-01

    There are no conventional lymphatics in the brain but physiological studies have revealed a substantial and immunologically significant lymphatic drainage from brain to cervical lymph nodes. Cerebrospinal fluid drains via the cribriform plate and nasal mucosa to cervical lymph nodes in rats and sheep and to a lesser extent in humans. More significant for a range of human neurological disorders is the lymphatic drainage of interstitial fluid (ISF) and solutes from brain parenchyma along capillary and artery walls. Tracers injected into grey matter, drain out of the brain along basement membranes in the walls of capillaries and cerebral arteries. Lymphatic drainage of antigens from the brain by this route may play a significant role in the immune response in virus infections, experimental autoimmune encephalomyelitis and multiple sclerosis. Neither antigen-presenting cells nor lymphocytes drain to lymph nodes by the perivascular route and this may be a factor in immunological privilege of the brain. Vessel pulsations appear to be the driving force for the lymphatic drainage along artery walls, and as vessels stiffen with age, amyloid peptides deposit in the drainage pathways as cerebral amyloid angiopathy (CAA). Blockage of lymphatic drainage of ISF and solutes from the brain by CAA may result in loss of homeostasis of the neuronal environment that may contribute to neuronal malfunction and dementia. Facilitating perivascular lymphatic drainage of amyloid-beta (Abeta) in the elderly may prevent the accumulation of Abeta in the brain, maintain homeostasis and provide a therapeutic strategy to help avert cognitive decline in Alzheimer's disease.

  20. Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms.

    Science.gov (United States)

    Becker, F; Yi, P; Al-Kofahi, M; Ganta, V C; Morris, J; Alexander, J S

    2014-03-01

    Alterations in the intestinal lymphatic network are well-established features of human and experimental inflammatory bowel disease (IBD). Such lymphangiogenic expansion might enhance classic intestinal lymphatic transport, eliminating excess accumulations of fluid, inflammatory cells and mediators, and could therefore be interpreted as an 'adaptive' response to acute and chronic inflammatory processes. However, whether these new lymphatic vessels are functional, unregulated or immature (and what factors may promote 'maturation' of these vessels) is currently an area under intense investigation. It is still controversial whether impaired lymphatic function in IBD is a direct consequence of the intestinal inflammation, or a preceding lymphangitis-like event. Current research has uncovered novel regulatory factors as well as new roles for familiar signaling pathways, which appear to be linked to inflammation-induced lymphatic alterations. The current review summarizes mechanisms amplifying lymphatic dysregulation and remodeling in intestinal inflammation at the organ, cell and molecular levels and discusses the influence of lymphangiogenesis and intestinal lymphatic transport function as they relate to IBD pathophysiology.

  1. Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage

    National Research Council Canada - National Science Library

    Iolyeva, Maria; Aebischer, David; Proulx, Steven T; Willrodt, Ann-Helen; Ecoiffier, Tatiana; Häner, Simone; Bouchaud, Grégory; Krieg, Carsten; Onder, Lucas; Ludewig, Burkhard; Santambrogio, Laura; Boyman, Onur; Chen, Lu; Finke, Daniela; Halin, Cornelia

    2013-01-01

    ...(-/-) mice, dermal lymphatic vessels (LVs) were abnormally organized and lymphatic drainage was compromised, transgenic overexpression of IL-7 in mice resulted in an expanded dermal LV network with increased drainage function...

  2. Gardening in the zone of death: an experimental assessment of the absolute elevation limit of vascular plants.

    Science.gov (United States)

    Dvorský, Miroslav; Chlumská, Zuzana; Altman, Jan; Čapková, Kateřina; Řeháková, Klára; Macek, Martin; Kopecký, Martin; Liancourt, Pierre; Doležal, Jiří

    2016-04-13

    Vascular plants in the western Tibetan Plateau reach 6000 m--the highest elevation on Earth. Due to the significant warming of the region, plant ranges are expected to shift upwards. However, factors governing maximum elevational limits of plant are unclear. To experimentally assess these factors, we transplanted 12 species from 5750 m to 5900 m (upper edge of vegetation) and 6100 m (beyond range) and monitored their survival for six years. In the first three years (2009-2012), there were plants surviving beyond the regional upper limit of vegetation. This supports the hypothesis of dispersal and/or recruitment limitation. Substantial warming, recorded in-situ during this period, very likely facilitated the survival. The survival was ecologically a non-random process, species better adapted to repeated soil freezing and thawing survived significantly better. No species have survived at 6100 m since 2013, probably due to the extreme snowfall in 2013. In conclusion, apart from the minimum heat requirements, our results show that episodic climatic events are decisive determinants of upper elevational limits of vascular plants.

  3. Does vitamin C deficiency increase lifestyle-associated vascular disease progression? Evidence based on experimental and clinical studies.

    Science.gov (United States)

    Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2013-12-10

    Despite continuous advances in the prevention of cardiovascular disease (CVD), critical issues associated with an unhealthy lifestyle remain an increasing cause of morbidity and mortality in industrialized countries. A growing body of literature supports a specific role for vitamin C in a number of reactions that are associated with vascular function and control including, for example, nitric oxide bioavailability, lipid metabolism, and vascular integrity. A large body of epidemiological evidence supports a relationship between poor vitamin C status and increased risk of developing CVD, and the prevalence of deficiency continues to be around 10%-20% of the general Western population although this problem could easily and cheaply be solved by supplementation. However, large intervention studies using vitamin C have not found a beneficial effect of supplementation. This review outlines the proposed mechanism by which vitamin C deficiency worsens CVD progression. In addition, it discusses problems with the currently available literature, including the discrepancies between the large intervention studies and the experimental and epidemiological literature. Increased insights into vitamin C deficiency-mediated CVD progression will enable the design of future randomized controlled trials that are better suited to test the efficacy of vitamin C in disease prevention as well as the identification of high-risk individuals which could possibly benefit from supplementation.

  4. The importance of lymphatic drainage in physiotherapy

    OpenAIRE

    VINKLEROVÁ, Miroslava

    2011-01-01

    The theoretical part summarizes all the theoretical knowledge on the topic. I am presenting a brief history of the discovery of the lymphatic vessels and the lymphatic drainage, the lymphatic system anatomy and its functions in the human body. Next, I have defined the concept of lymphoedema and divided it by its origin to primary and secondary lymphedema. The work includes the diagnosis of lymphedema , both conservative and surgical treatment options, indications and contraindications of lymp...

  5. Interplay between Inflammatory Responses and Lymphatic Vessels

    OpenAIRE

    Shin, Kihyuk; Lee, Seung-Hyo

    2014-01-01

    Lymphatic vessels are routes for leukocyte migration and fluid drainage. In addition to their passive roles in migration of leukocytes, increasing evidence indicates their active roles in immune regulation. Tissue inflammation rapidly induces lymphatic endothelial cell proliferation and chemokine production, thereby resulting in lymphangiogenesis. Furthermore, lymphatic endothelial cells induce T cell tolerance through various mechanisms. In this review, we focus on the current knowledge on h...

  6. 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

  7. 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.

  8. Lymphatic function and responses in periodontal disease.

    Science.gov (United States)

    Berggreen, Ellen; Wiig, Helge

    2014-07-15

    Extravasated fluid, proteins and cells are returned into the circulation by lymphatic vessels that are also important in immune cell trafficking. Lymphatic vessels in gingiva are located in lamina propria, and traverse the external surface of the alveolar bone. Lack of gingival lymphatics has been shown to increase the interstitial fluid pressure and fluid volume, thus showing that lymphatics are important for fluid drainage also in this tissue. Gingival lymphatic vessels require continuous signaling by the growth factors VEGF-C and D via their receptor VEGFR-3 for their maintenance, factors that are expressed in the gingival epithelium and also in immune cells in lamina propria. VEGF-C seems to be of critical importance for lymphangiogeneses induced during periodontal disease development. Mice are protected against periodontitis by lymphatics clearing bacteria and bacterial products and promoting humoral immune responses. CCL21, a ligand important for dendritic cell migration, has been found to be downregulated in lymphatics from patients with periodontitis. Such patients may have impaired gingival lymphatic function due to high enzymatic activity and thus loss of structural components in the interstitium. At present there are few studies on the role of lymphatic vessels in periodontal disease making this a rather unexplored field. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Acute neonatal presentation of a lymphatic malformation.

    Science.gov (United States)

    Tang, Chee Yan; Wijnen, M; Sambeeck van, S J; Halbertsma, F J J

    2013-08-01

    Oropharyngeal lymphatic malformations usually present with a mass either at birth or in the first 2 years of life. Rarely, lymphatic malformations present with extremely progressive respiratory problems shortly after birth, and usually occur in cases which have remained undetected in the absence of antenatal ultrasound. We report the case of a newborn that required tracheostomy and gastrostomy due to a rapidly expansive lymphatic malformation. MRI showed multilocular microcystic lymphatic malformation. Intralesional bleomycin injections proved to be successful in this patient. A short review of epidemiology, clinical manifestation and treatment is given.

  10. Plasmodium falciparum histidine-rich protein II causes vascular leakage and exacerbates experimental cerebral malaria in mice.

    Science.gov (United States)

    Pal, Priya; Balaban, Amanda E; Diamond, Michael S; Sinnis, Photini; Klein, Robyn S; Goldberg, Daniel E

    2017-01-01

    A devastating complication of Plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. P. falciparum produces a protein called histidine-rich protein II (HRPII) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. Using a human cerebral microvascular endothelial barrier model, we previously found that HRPII activates the endothelial cell inflammasome, resulting in decreased integrity of tight junctions and increased endothelial barrier permeability. Here, we report that intravenous administration of HRPII induced blood-brain barrier leakage in uninfected mice. Furthermore, HRPII infusion in P. berghei-infected mice increased early mortality from experimental cerebral malaria. These data support the hypothesis that HRPII is a virulence factor that contributes to cerebral malaria by compromising the integrity of the blood-brain barrier.

  11. Requirement for Tumor Necrosis Factor Receptor 2 Expression on Vascular Cells To Induce Experimental Cerebral Malaria

    OpenAIRE

    Stoelcker, Benjamin; Hehlgans, Thomas; Weigl, Karin; Bluethmann, Horst; Grau, Georges E.; Männel, Daniela N.

    2002-01-01

    Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating bone marrow chimeras which express TNFR2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria.

  12. Characterization of internodal collecting lymphatic vessel function after surgical removal of an axillary lymph node in mice

    Science.gov (United States)

    Kwon, Sunkuk; Price, Roger E.

    2016-01-01

    Secondary lymphedema is an acquired lymphatic disorder, which occurs because of damage to the lymphatic system from surgery and/or radiation therapy for cancer treatment. However, it remains unknown how post-nodal collecting lymphatic vessels (CLVs) draining to the surgical wound area change in response to lymphadenectomy. We investigated functional and architectural changes of inguinal-to-axillary internodal CLVs (ICLVs) in mice after a single axillary LN (ALN) dissection using near-infrared fluorescence imaging. Our data showed no lymph flow in the ICLVs draining from the inguinal LN (ILN) at 2 days post-surgery. External compression enabled visualization of a small segment of contractile fluorescent ICLVs, but not all the way to the axillary region. At day 6, abnormal lymphatic drainage patterns, including lateral and retrograde lymph flow via vessels branching off the ICLVs were observed, which started to disappear beginning 9 days after surgery. The administration of vascular endothelial growth factor (VEGF)-C into the wound increased resolution of altered lymphatic drainage. Lymphatic drainage from the base of the tail to the ILN did not significantly change over time. These results demonstrate that lymph flow in the CLVs is dramatically affected by a LN dissection and long-term interruption of lymph flow might cause CLV dysfunction and thus contribute to chronic lymphatic disorders. PMID:27446639

  13. Magnetic Particle Imaging (MPI): Experimental Quantification of Vascular Stenosis Using Stationary Stenosis Phantoms.

    Science.gov (United States)

    Vaalma, Sarah; Rahmer, Jürgen; Panagiotopoulos, Nikolaos; Duschka, Robert L; Borgert, Jörn; Barkhausen, Jörg; Vogt, Florian M; Haegele, Julian

    2017-01-01

    Magnetic Particle Imaging (MPI) is able to provide high temporal and good spatial resolution, high signal-to-noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs). Because of that, MPI is proposed to be a promising future method for cardiovascular imaging. Here, an interesting application may be the quantification of vascular pathologies like stenosis by utilizing the proportionality of the SPIO concentration and the MPI signal strength. In this study, the feasibility of MPI based stenosis quantification is evaluated based on this application scenario. Nine different stenosis phantoms with a normal diameter of 10 mm each and different stenoses of 1-9 mm and ten reference phantoms with a straight diameter of 1-10 mm were filled with a 1% Resovist dilution and measured in a preclinical MPI-demonstrator. The MPI signal intensities of the reference phantoms were compared to each other and the change of signal intensity within each stenosis phantom was used to calculate the degree of stenosis. These values were then compared to the known diameters of each phantom. As a second measurement, the 5 mm stenosis phantom was used for a serial dilution measurement down to a Resovist dilution of 1:3200 (0.031%), which is lower than a first pass blood concentration of a Resovist bolus in the peripheral arteries of an average adult human of at least about 1:1000. The correlation of the stenosis values based on MPI signal intensity measurements and based on the known diameters showed a very good agreement, proving the high precision of quantitative MPI in this regard.

  14. Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase

    NARCIS (Netherlands)

    van Loon, Rosa Laura E; Bartelds, Beatrijs; Wagener, Frank A D T G; Affara, Nada; Mohaupt, Saffloer; Wijnberg, Hans; Pennings, Sebastiaan W C; Takens, Janny; Berger, Rolf M F

    2015-01-01

    BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial

  15. Large facial lymphatic malformation treatment using sclerosing agent followed by surgical resection: clinical and pathology report.

    Science.gov (United States)

    Laviv, Amir; Maly, Alexander; Abu-Tair, Jawad

    2017-07-22

    Lymphatic malformations are rare slow-flow vascular malformations, with high tendency to appear in the head and neck region. The treatment of these lesions ranges from follow-up to sclerosing agent injection to surgical excision. The authors present a case of a new born with large extensive lingual and submandibular lymphatic malformation, for which the patient underwent tracheostomy and gastrostomy insertion. He was then treated successfully with sclerosing agent injections followed by surgical excision, with 7 years follow-up. The second case presented is a two and a half baby with large lingual lymphatic malformation, treated successfully with doxycycline injections followed by intraoral excision of the lesion. Pathology of the excised lesion is then demonstrated, which shows for the first time the different layers affected by the sclerosing agent.

  16. The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Lucchetta, Luca; Monge-Garcia, M Ignacio; Borges, Joao Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-03-01

    To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. Experimental study. Animal research laboratory. Ten pigs, 35 ± 5.2 kg. Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves. After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p mechanics compared with higher or lower positive end-expiratory pressure settings.

  17. Lymphatic pumping: mechanics, mechanisms and malfunction

    Science.gov (United States)

    Scallan, Joshua P.; Zawieja, Scott D.; Castorena‐Gonzalez, Jorge A.

    2016-01-01

    Abstract A combination of extrinsic (passive) and intrinsic (active) forces move lymph against a hydrostatic pressure gradient in most regions of the body. The effectiveness of the lymph pump system impacts not only interstitial fluid balance but other aspects of overall homeostasis. This review focuses on the mechanisms that regulate the intrinsic, active contractions of collecting lymphatic vessels in relation to their ability to actively transport lymph. Lymph propulsion requires not only robust contractions of lymphatic muscle cells, but contraction waves that are synchronized over the length of a lymphangion as well as properly functioning intraluminal valves. Normal lymphatic pump function is determined by the intrinsic properties of lymphatic muscle and the regulation of pumping by lymphatic preload, afterload, spontaneous contraction rate, contractility and neural influences. Lymphatic contractile dysfunction, barrier dysfunction and valve defects are common themes among pathologies that directly involve the lymphatic system, such as inherited and acquired forms of lymphoedema, and pathologies that indirectly involve the lymphatic system, such as inflammation, obesity and metabolic syndrome, and inflammatory bowel disease. PMID:27219461

  18. Lymphatic vessels in osteoarthritic human knees.

    Science.gov (United States)

    Walsh, D A; Verghese, P; Cook, G J; McWilliams, D F; Mapp, P I; Ashraf, S; Wilson, D

    2012-05-01

    The distribution and function of lymphatic vessels in normal and diseased human knees are understood incompletely. This study aimed to investigate whether lymphatic density is associated with clinical, histological or radiographic parameters in osteoarthritis (OA). Sections of synovium from 60 knees from patients with OA were compared with 60 post mortem control knees (from 37 individuals). Lymphatic vessels were identified using immunohistochemistry for podoplanin, and quantified as lymphatic vessel density (LVD) and lymphatic endothelial cell (LEC) fractional area. Effusion status was determined by clinical examination, radiographs were scored for OA changes, and inflammation grading used haematoxylin and eosin stained sections of synovium. Lymphatic vessels were present in synovia from both disease groups, but were not identified in subchondral bone. Synovial lymphatic densities were independent of radiological severity and age. Synovia from patients with OA displayed lower LVD (z=-3.4, P=0.001) and lower LEC fractional areas (z=-4.5, Plymphatics and OA/effusion appeared to be independent of other measured confounders. Lymphatic vessels are present in lower densities in OA synovia. Abnormalities of synovial fluid drainage may confound the value of effusion as a clinical sign of synovitis in OA. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. Acute neonatal presentation of a lymphatic malformation

    NARCIS (Netherlands)

    Tang, C.Y.; Wijnen, M.H.; Sambeeck, S.J. van; Halbertsma, F.J.

    2013-01-01

    Oropharyngeal lymphatic malformations usually present with a mass either at birth or in the first 2 years of life. Rarely, lymphatic malformations present with extremely progressive respiratory problems shortly after birth, and usually occur in cases which have remained undetected in the absence of

  20. Análise da remodelação vascular na isquemia pulmonar experimental, nas fases aguda e crônica Analysis of acute and chronic vascular remodeling in an experimental model of pulmonary ischemia

    Directory of Open Access Journals (Sweden)

    Wanderley M. Bernardo

    2005-02-01

    Full Text Available INTRODUÇÃO: Alterações estruturais da circulação pulmonar traduzem processo de remodelação vascular e têm relação provável com variações locais de fluxo e isquemia. OBJETIVO: Definir as alterações histológicas na circulação pulmonar após obstrução experimental da artéria pulmonar. Correlacioná-las com os padrões de redistribuição sangüínea e remodelação vascular. MÉTODO: Foram submetidos à toracotomia esquerda 48 ratos Wistar, alocados aleatoriamente em dois grupos, com ligadura da artéria pulmonar e controle, e sacrificados com 1, 7, 30 e 60 dias. Nos pulmões retirados avaliou-se presença de sinais de injúria no parênquima e mensurou-se diâmetro externo e espessura da parede das arteríolas de bronquíolos terminais, respiratórios e alveolares. Diâmetro interno e porcentagem de espessura da parede foram calculados. RESULTADOS: Só ocorreu infarto, necrose e hemorragia no pulmão isquêmico. No não isquêmico houve aumento mantido dos diâmetros externo e interno das arteríolas, com redução inicial da espessura no 1º dia e valores semelhantes aos do grupo controle no 60º dia. No pulmão isquêmico houve redução transitória nos diâmetros externo e interno das arteríolas de bronquíolos terminais e respiratórios, com aumento, inicial e transitório, na sua espessura. As arteríolas alveolares apresentaram aumento do diâmetro externo e espessura da parede, com redução do diâmetro interno, mantida e progressiva. CONCLUSÃO: Este modelo reproduz arteriopatia distal em pacientes com tromboembolismo pulmonar crônico. A resposta vascular no pulmão não isquêmico é compatível com padrão de remodelação de hiperfluxo; a no pulmão isquêmico com hipofluxo e isquemia. Nas arteríolas de bronquíolos terminais e respiratórios a resposta foi transitória. Nas alveolares foi progressiva e mantida, pela provável ocorrência tardia de hiperfluxo local.BACKGROUND: Structural alterations to the

  1. Expression of VEGF-D in epithelial ovarian cancer and its relationship to lymphatic metastasis.

    Science.gov (United States)

    He, Lixia; He, Junyong; Zhao, Xia

    2016-03-01

    To investigate the contribution of vascular endothelial growth factor (VEGF)-D to tumor progression, tumor lymphangiogenesis and lymphatic metastasis in epithelial ovarian cancer. The expression profiles of VEGF-D in 18 benign, 14 borderline and 87 malignant epithelial ovarian cancers were examined using immunohistochemical (IHC) staining. Lymphatic vessels were identified using IHC staining on lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), which is a lymph-specific receptor for hyaluronan in identifying lymphatic vessels. The potential correlation among VEGF-D, lymphatic vessel density (LVD) and clinico-pathological factors of the epithelial ovarian cancer was also analyzed. Positive IHC staining of VEGF-D was observed in 17% of benign, 21% of borderline and 80% of malignant epithelial ovarian tumors specimens. In the epithelial ovarian cancer specimens, the LVD was 3.41 ± 2.37 in the VEGF-D negative (17 patients), 5.42 ± 3.49 in the weak (26 patients), 7.22 ± 2.36 in the moderate (27 patients) and 7.35 ± 4.06 in the strong (17 patients) groups, respectively. Additionally, the expression of VEGF-D was positively correlated with LVD (r = 0.415, P ovarian cancer than in lymph node-negative patients (P = 0.009, P ovarian cancer. © 2013 Wiley Publishing Asia Pty Ltd.

  2. 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.

  3. Current Status, Pitfalls and Future Directions in the Diagnosis and Therapy of Lymphatic Malformation.

    Science.gov (United States)

    Sun, Ravi W; Tuchin, Valery V; Zharov, Vladimir P; Galanzha, Ekaterina I; Richter, Gresham T

    2017-08-29

    Lymphatic malformations (LM) are complex congenital vascular lesions composed of dilated, abnormal lymphatic channels of varying size that can result in significant aesthetic and physical impairment due to relentless growth. LMs comprised of micro-lymphatic channels (microcystic) integrate and infiltrate normal soft tissue, leading to a locally invasive mass. Ultrasonography (US) and magnetic resonance imaging (MRI) assist in the diagnosis but are unable to detect microvasculature present in microcystic LM. In this review, we examine existing tools and elaborate on alternative diagnostic methods in assessing LM. In particular, photoacoustics (PA), low-toxicity nanoparticles and optical clearing can overcome existing challenges in the examination of lymphatic channels in vivo. In combination with photothermal (PT) cytometry/flow cytometry (FC), PA may provide a versatile tool for lymphatic-related clinical applications, potentially leading to a single diagnostic and therapeutic platform to overcome limitations in current imaging techniques and permit targeted theranostics of microcystic LM. This article is protected by copyright. All rights reserved.

  4. Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats.

    Science.gov (United States)

    Minutoli, Letteria; Arena, Salvatore; Bonvissuto, Giulio; Bitto, Alessandra; Polito, Francesca; Irrera, Natasha; Arena, Francesco; Fragalà, Eugenia; Romeo, Carmelo; Nicotina, Piero Antonio; Fazzari, Carmine; Marini, Herbert; Implatini, Alessandra; Grimaldi, Silvia; Cantone, Noemi; Di Benedetto, Vincenzo; Squadrito, Francesco; Altavilla, Domenica; Morgia, Giuseppe

    2011-03-15

    In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Polydeoxyribonucleotide administration improves the intra-testicular vascularization in rat experimental varicocele.

    Science.gov (United States)

    Arena, Salvatore; Minutoli, Letteria; Arena, Francesco; Nicotina, Piero Antonio; Romeo, Carmelo; Squadrito, Francesco; Altavilla, Domenica; Morgia, Giuseppe; Magno, Carlo

    2012-01-01

    To study the effect of PDRN on angiogenesis in a model of varicocele in rats. After the creation of experimental varicocele, rats were randomized to one of the four treatments: vehicle, PDRN, DMPX, and PDRN plus DMPX. Twenty-one days after randomization, all animals were euthanized and the left testis was harvested. Academic hospital. Male Sprague-Dawley rats were used. A clamp was passed behind the left renal vein distally to the spermatic vein insertion. A silk ligature was placed around the left renal vein at this site and was tied over the top of a probe. The latter was then withdrawn and the vein was allowed to expand. In shams, a suture was placed but it was not tied. To assess testicular microvascular density using CD34 immunostaining. Microvascular density in the varicocele plus PDRN group was significantly higher than in other groups. PDRN could represent a novel therapeutic strategy for varicocele treatment in subfertile patients, improving the innate pathophysiologic mechanism of neoangiogenesis, through compensatory oxygen and metabolite supply to tubular and extratubular testicular compartments. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Hobnail hemangioma reclassified as superficial lymphatic malformation: a study of 52 cases.

    Science.gov (United States)

    Trindade, Felicidade; Kutzner, Heinz; Tellechea, Óscar; Requena, Luis; Colmenero, Isabel

    2012-01-01

    Hobnail hemangioma (HH) is currently classified as a benign vascular tumor, although it is not well understood whether this lesion differentiates toward blood or lymphatic endothelial cells. Immunostaining with the endothelial marker Wilms tumor 1 (WT1) helps distinguish between vascular neoplasms and malformations, being positive in the former and negative in the latter. We sought to investigate WT1, human herpesvirus 8 latent nuclear antigen, D2-40, and Ki-67 immunoprofile in HH, to gain further insight into its histogenesis. We evaluated 52 HHs collected in Dermatohistopathologische Gemeinschaftslabor, Friedrichshafen, Germany. Immunohistochemical expression of WT1 was performed in all cases. Ten of 52 lesions were also studied for D2-40 and Ki-67 staining and 12 lesions were stained for human herpesvirus 8 latent nuclear antigen. All 52 HHs were completely negative for WT1 immunostaining. Immunohistochemistry performed in 10 HHs showed diffuse and strong positive staining for D2-40 in 8 lesions and focal positivity in two. All cases tested showed negative staining for Ki-67 and human herpesvirus 8 latent nuclear antigen. There are no limitations. Although the exact histogenesis of HH is unknown, most of the performed immunohistochemical studies support a lymphatic line of differentiation. However, on the basis of the WT1 negativity, we believe that HH is better considered as a lymphatic malformation rather than a lymphatic neoplasm. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  7. [Morphogenesis, structure and properties of lymphatic vessels].

    Science.gov (United States)

    Ratajska, Anna; Jankowska-Steifer, Ewa; Czarnowska, Elżbieta; Flaht, Aleksandra; Radomska-Leśniewska, Dorota

    2012-11-19

    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 a source of growth

  8. Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction.

    Directory of Open Access Journals (Sweden)

    Nicola N Lynskey

    2015-09-01

    Full Text Available The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology.

  9. 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

    and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxic conditions, arterial-lymphatic conduits (ALCs) became highly dilated and linearized by NO...

  10. [Management of lymphatic malformations in oral and maxillofacial regions: the rationale according to the new classification].

    Science.gov (United States)

    Zheng, Jia-wei; Qin, Zhong-ping; Zhang, Zhi-yuan

    2005-12-01

    According to the classification of ISSVA, Waner and Suen, the traditionally called lymphangiomas are now referred to as lymphatic malformations, including both macrocystic and microcystic lesions. They are commonly seen vascular anomalies, and most frequently diagnosed at birth and most often occur in the head and neck area. The etiology of lymphatic malformations is still unknown, resulting in a variety of treatment modalities. This paper reviewed the recent literatures with respect to the indications, contraindications, advantages and disadvantages of surgical excision, sclerotherapy and laser ablation of lymphatic malformations of the head and neck, with detailed discussion of the advances in molecular biology and clinical treatment prospects. It is concluded that although lymphatic malformations are benign lesions, they seldom involute spontaneously. Of all vascular malformations, lymphatic malformations are the most difficult to be eradicated. Their infiltrating nature coupled with the difficulty in distinguishing involved important structures of the head and neck from adjacent normal tissues makes complete surgical extirpation even more difficult. The likelihood of postsurgical recurrence and complications is thus higher than other vascular lesions. Although many treatment protocols are available in clinic, indications, contraindications, advantages and disadvantages exist in each modality. The selection of treatment modalities should depend on the patients' status and techniques available. The treatment protocol should be individualized and comprehensive as well as sequential, in order to obtain the best treatment outcomes. In general, treatment will vary according to the depth and the extent of the lesions. Superficial mucosal microcystic lesions and cervicofacial macrocystic lesions are amenable to ablation with sclerotherapy using Bleomycin and OK-432 with the advantages of the absence of a surgical scar. The sclerosing agent OK-432 is effective for

  11. The discovery of the synovial lymphatic stomata and lymphatic reabsorption in knee effusion.

    Science.gov (United States)

    Ping, Zepeng; Jiang, Tingting; Wang, Chong; Chen, Zhongyi; Chen, Zhongliang; Wang, Jiaxiong; Wang, Li; Wang, Beibei; Xu, Dandan; Liu, Changming; Li, Zhongjie; Li, Ji-Cheng

    2015-06-01

    To illustrate the mechanism of lymphatic reabsorption in knee joint effusion. The current investigation employed transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques to reveal the ultrastructure of the knee synovial membrane in New Zealand rabbits and human. Ultrastructural changes of the synovial lymphatic stomata were observed by using trypan blue absorption and sodium hydroxide (NaOH) digestion methods, and the animal models of synovitis. New Zealand rabbits and human synovial membranes were composed of two types of synovial cells: type A and type B. No lymphatic stomata were found among type A synovial cells, whereas lymphatic stomata with the diameters ranging 0.74-3.26 µm were found in type B synovial cells, and some stomata were closed. After the NaOH digestion, a number of sieve pores, similar to lymphatic stomata in size and shape, were observed in the dense fibrous connective tissue underneath the type B synovial cells. After injecting trypan blue into the rabbit knee joint cavity, absorption of trypan blue through the lymphatic stomata was observed, suggesting the absorption function of the synovial lymphatic stomata. In the rabbit knee joint synovitis models, the synovial lymphatic stomata diameter enlarged. Some macrophages migrated from the lymphatic stomata, indicating that the synovial lymphatic stomata were involved in the joint effusion absorption and inflammatory response. Our study is the first to report the existence of synovial lymphatic stomata in the New Zealand rabbits and human knee joints. Lymphatic stomata may have an important role in the reabsorption of joint effusion. © 2015 Wiley Periodicals, Inc.

  12. Lymphatic malformation: risk of progression during childhood and adolescence.

    Science.gov (United States)

    Hassanein, Aladdin H; Mulliken, John B; Fishman, Steven J; Quatrano, Nicola A; Zurakowski, David; Greene, Arin K

    2012-01-01

    Lymphatic malformations (LMs) in soft tissues tend to enlarge over time, causing distortion, obstruction, and functional problems. The purpose of this study was to determine the natural progression of LMs to facilitate patient counseling, gain insight into pathophysiology, and guide therapy. Our Vascular Anomalies Center database was reviewed for patients with cutaneous and soft tissue LMs; combined or visceral lesions were excluded. Predictive variables were age, channel type (macrocystic, microcystic, combined), sex, lesion size (localized, diffuse), and location (head/neck, extremities, trunk). The outcome variable was natural progression of the malformation defined by expansion or the onset/worsening of signs and symptoms. The study included 441 patients: 234 females (53.1%) and 207 males (46.9%). Lymphatic malformations were located in the head/neck (61.2%), extremities (17.5%), trunk (16.1%), or multiple sites (5.2%). Children had a 42.2% risk of progression before adolescence, 84.7% before adulthood, and 95.3% during their lifetime. Progression was more likely in adolescence (63.8%) than in childhood (40.8%); the odds ratio was 2.6 (P=0.003). Diffuse LMs worsened more often than localized lesions (P=0.001), whereas channel type (P=0.63), sex (P=0.42), and location (P=0.28) did not influence progression.Lymphatic malformations have a greater risk of progression in adolescence than in childhood; pubertal hormones may contribute to expansion. Because of this high rate of progression, early treatment of asymptomatic LMs should be considered.

  13. Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphoedema model.

    Science.gov (United States)

    Pivetta, Eliana; Wassermann, Bruna; Del Bel Belluz, Lisa; Danussi, Carla; Modica, Teresa Maria Elisa; Maiorani, Orlando; Bosisio, Giulia; Boccardo, Francesco; Canzonieri, Vincenzo; Colombatti, Alfonso; Spessotto, Paola

    2016-07-01

    Lymphatic vasculature critically depends on the connections of lymphatic endothelial cells with the extracellular matrix (ECM), which are mediated by anchoring filaments (AFs). The ECM protein EMILIN1 is a component of AFs and is involved in the regulation of lymphatic vessel functions: accordingly, Emilin1(-/-) mice display lymphatic vascular morphological alterations, leading to functional defects such as mild lymphoedema, lymph leakage and compromised lymph drainage. In the present study, using a mouse post-surgical tail lymphoedema model, we show that the acute phase of acquired lymphoedema correlates with EMILIN1 degradation due to neutrophil elastase (NE) released by infiltrating neutrophils. As a consequence, the intercellular junctions of lymphatic endothelial cells are weakened and drainage to regional lymph nodes is severely affected. The local administration of sivelestat, a specific NE inhibitor, prevents EMILIN1 degradation and reduces lymphoedema, restoring a normal lymphatic functionality. The finding that, in human secondary lymphoedema samples, we also detected cleaved EMILIN1 with the typical bands of an NE-dependent pattern of fragmentation establishes a rationale for a powerful strategy that targets NE inhibition. In conclusion, the attempts to block EMILIN1 degradation locally represent the basis for a novel 'ECM' pharmacological approach to assessing new lymphoedema treatments. © 2016 The Author(s).

  14. Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

    Science.gov (United States)

    Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

    2016-01-01

    The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Lymphatic drainage of the external ear.

    Science.gov (United States)

    Pan, Wei-Ren; le Roux, Cara Michelle; Levy, Sidney M; Briggs, Christopher A

    2011-01-01

    Lymphoscintigraphy reveals inconsistencies in our knowledge of the lymphatic anatomy of the external ear. Fifteen external ears from 9 unembalmed human cadavers were studied. Six percent hydrogen peroxide was used to find the lymphatic vessels using a surgical microscope. They were injected with a radio-opaque mixture, dissected, photographed, and radiographed to demonstrate lymphatic vessels in the tissue. Final results were transferred to the computer for analysis. Four groups of lymph collecting vessels were found. The anterior branch, in all specimens, drained directly or indirectly (having merged with a vessel descending from the scalp) into the preauricular lymph nodes. The superior, middle, and inferior (lobule) branches drained to their multiple first tier lymph nodes. An accurate lymphatic map of the external ear is described to upgrade our anatomic knowledge. It will be of benefit for the clinical management of malignancies in this region. © 2010 Wiley Periodicals, Inc. Head Neck, 2011.

  16. Prenatally-detected giant lymphatic malformation.

    Science.gov (United States)

    Sværdborg, Mille; Keller, Johnny; Schrøder, Henrik; Petersen, Olav B; Stausbøl-Grøn, Brian; Engberg Damsgaard, Tine

    2011-12-01

    We present a case of a giant lymphatic malformation of the chest and abdominal wall that was diagnosed in the third trimester of pregnancy. It was treated by one stage excision with good functional and cosmetic outcomes.

  17. Lymphatic Filariasis: Frequently Asked Questions (FAQs)

    Science.gov (United States)

    ... FAQs) Vectors of Lymphatic Filariasis Epidemiology & Risk Factors Biology ... microscopic, thread-like worms. The adult worms only live in the human lymph system. The lymph system maintains the body's fluid balance ...

  18. Pneumocystis carinii Pneumonia in Acute Lymphatic Leukaemia ...

    African Journals Online (AJOL)

    A case report of a patient who developed fatal pneumocystis pneumonia while in remission from acute lymphatic leukaemia is presented. Clinical and aetiological aspects of this rare infection are discussed. Attention is drawn to diagnostic pitfalls encountered in leukaemia.

  19. Clinical epidemiology of lymphatic filariasis and community ...

    African Journals Online (AJOL)

    , this study employed the use of lymphatic filariasis–related clinical signs as rapid diagnostic features, immunochromatographic card test (ICT) to detect circulating filarial antigen (CFA) and questionnaire to investigate community perceptions ...

  20. Efficacy of bosentan, a dual ETA and ETB endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.

    Science.gov (United States)

    Singh, Gurpreet; Sharma, Bhupesh; Jaggi, Amteshwar Singh; Singh, Nirmal

    2014-09-01

    The study was designed to investigate the efficacy of bosentan a dual endothelin (ETA and ETB) receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia. Diabetes was induced in rats by administration of a single dose (50mg/kg, i.p.) of streptozotocin (STZ). Drug treatment was started after 1 month of STZ administration and treatment was continued until the end of the study. Morris water maze (MWM) test was employed for testing spatial learning and memory. Endothelial function was measured on isolated aortic rings using student physiograph. Serum glucose, body weight, serum nitrite/nitrate, brain thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH) levels, and brain acetylcholinesterase activity were also tested. STZ treatment resulted in significant development of cognitive and vascular endothelial deficits, manifested in the terms of endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate levels along with increase in serum glucose, brain acetylcholinesterase activity, TBARS, and decreased GSH levels. Treatment of bosentan attenuated diabetes induced impairment of learning, memory, endothelial function, and various biochemical parameters. It may be concluded that bosentan has shown efficacy in STZ induced cognitive and vascular endothelial deficits. Thus, endothelin receptors can be considered as a potential pharmacological target for the management of experimental diabetes induced vascular endothelial dysfunction and associated dementia. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Site-specific induction of lymphatic malformations in a rat model for image-guided therapy

    Energy Technology Data Exchange (ETDEWEB)

    Short, Robert F.; Shiels, William E. [Ohio State University College of Medicine and Public Health, Department of Radiology, The Children' s Radiological Institute, Children' s Hospital, Columbus, OH (United States); Sferra, Thomas J. [Ohio State University College of Medicine and Public Health, Department of Gastroenterology, The Columbus Children' s Research Institute, Children' s Hospital, Columbus, OH (United States); Nicol, Kathleen K. [Ohio State University College of Medicine and Public Health, Department of Pathology, Children' s Hospital, Columbus, OH (United States); Schofield, Minka; Wiet, Gregory J. [Ohio State University College of Medicine and Public Health, Department of Otolaryngology, Children' s Hospital, Columbus, OH (United States)

    2007-06-15

    Lymphatic malformation is a common benign mass in children and adults and is representative of a derangement in lymphangiogenesis. These lesions have high recurrence rates and significant morbidity associated with surgery. Several sclerotherapy regimens have been developed clinically to treat lymphatic malformations; however, an animal model has not been developed that is adequate to test the efficacy of image-guided therapeutic interventions. To develop an animal model suitable for evaluation of percutaneous treatments of lymphatic malformations. Male Harlan Sprague-Dawley rats (n = 9) received two US-guided injections of Incomplete Freund's Adjuvant (IFA) over a 2-week period. All nine rats were injected twice into the peritoneum (IP); a subgroup (n = 3) received additional injections into the neck. Three animals that received IP injections of saline were used as controls. The injection sites were monitored for the development of lesions by high-resolution ultrasonography at 2-week intervals for 100 days. High-resolution (4.7 Tesla) magnetic resonance imaging was then performed on two animals noted to have developed masses. The rats were sacrificed and histologic examination of the identified lesions was performed, including immunohistochemical staining for vascular (CD31) and lymphatic (Flt-4 and Prox-1) endothelium. All animals injected with IFA developed cystic lesions. The three animals injected at dual sites were noted to have both microcystic and macrocystic malformations in the neck and microcystic plaque-like lesions in the peritoneum. The macrocystic malformations ({>=}5 mm) in the neck were detected by ultrasonography and grossly later during necropsy. Histopathologic analysis revealed the cystic spaces to be lined by lymphatic endothelium supported by a connective tissue stroma. Control animals did not exhibit detectable lesions with either ultrasonography or necropsy. This model represents a promising tool for translational development of image

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels.

    Science.gov (United States)

    Rehal, Sonia; Blanckaert, Pauline; Roizes, Simon; von der Weid, Pierre-Yves

    2009-12-01

    Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

  5. A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.

    Science.gov (United States)

    Haloob, Nora; Pepper, Christopher; Hartley, Benjamin

    2015-12-01

    Otolaryngologists will most frequently encounter extra-cranial glial tissue within the nasal cavity, where it is known as a 'nasal glioma', and may communicate with the dura. However, glial tissue can also present extra-nasally in the form of a neck mass with no intracranial connection. In these rare cases, they can present soon after birth as an enlarging neck mass, causing compressive symptoms with airway obstruction and feeding difficulties. In this way, it is often initially misdiagnosed as a more common lesion such as a lymphatic malformation, teratoma, branchial anomaly or vascular malformation. As with many congenital head and neck masses, offering the most the appropriate management relies heavily on radiological imaging and, where possible, histopathology from a diagnostic biopsy. Once the diagnosis of extra-nasal glial heterotopia has been confirmed, the gold standard management is complete surgical excision. We review three cases of extra-nasal glial heterotopia presenting to our institution over an eleven year period as a large neck mass, which mimicked other congenital neck lumps, and discuss them in the context of those in the literature. We highlight how their clinical and radiological features can easily be confused with lymphatic malformations, and the potential implications of misdiagnosis. Raising awareness of this diagnostic confusion will highlight the need for management of these cases within an appropriate paediatric multidisciplinary setting. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Immunopathogenesis of lymphatic filarial disease1

    OpenAIRE

    Babu, Subash; Thomas B Nutman

    2012-01-01

    Although two-thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~ 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and t...

  7. 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

  8. Comparative and Developmental Anatomy of Cardiac Lymphatics

    Directory of Open Access Journals (Sweden)

    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.

  9. Safety, Healing, and Efficacy of Vascular Prostheses Coated with Hydroxypropyl-[beta]-cyclodextrin Polymer: Experimental In Vitro and Animal Studies

    National Research Council Canada - National Science Library

    Jean-Baptiste, E; Blanchemain, N; Martel, B; Neut, C; Hildebrand, H.F; Haulon, S

    2012-01-01

    Polyester vascular prostheses (PVPs) coated with a polymer of hydroxypropyl-[beta]-cyclodextrin (HP[beta]CD) have been designed to provide an in situ reservoir for the sustained delivery of one or more bioactive molecules...

  10. Safety, healing, and efficacy of vascular prostheses coated with hydroxypropyl-β-cyclodextrin polymer: experimental in vitro and animal studies

    National Research Council Canada - National Science Library

    Jean-Baptiste, E; Blanchemain, N; Martel, B; Neut, C; Hildebrand, H F; Haulon, S

    2012-01-01

    Polyester vascular prostheses (PVPs) coated with a polymer of hydroxypropyl-β-cyclodextrin (HPβCD) have been designed to provide an in situ reservoir for the sustained delivery of one or more bioactive molecules...

  11. Experimental and numerical investigation on the transient vascular thermal response to multi-pulse Nd:YAG laser.

    Science.gov (United States)

    Li, Dong; Li, Ruohui; Jia, Hao; Chen, Bin; Wu, Wenjuan; Ying, Zhaoxia

    2017-11-01

    Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. Laser therapy is currently the most effective way in clinical practice for PWS. A 1,064 nm Nd:YAG laser in the near-infrared band can achieve a deeper treatment depth compared to the current widely adopted pulsed dye laser. However, because of its relatively weak absorption by blood, single-pulse Nd:YAG laser requires high energy density to cause effective vessel damage, but may inflict undesirable burning to surrounding collagen. Multi-pulse laser has great potential in clinical treatment because it needs less energy density for each pulse. This paper presented an experimental and theoretical study of the transient thermal effects of low-energy multi-pulse Nd:YAG laser on blood vessels. In vivo experiments were performed on dorsal skin chamber. By using a high speed camera (up to 2,000 fps), the complete and dynamic thermal response of blood vessels during laser irradiation and between pulse intervals was obtained. In vitro experiment in capillary tubes and Numerical simulations by two-scale heat transfer model were also conducted to further explore the in vivo experimental findings. The complete and dynamic response of blood vessels were obtained, including vessel dilation, thrombus formation, partial vessel constriction, thread-like constriction, cavitation and bubbles, and hemorrhage. Thread-like constriction is the desirable treatment end point, which will only occur after thrombus completely occludes the vessel lumen. Cavitation can cause hemorrhage when thrombus fails to occlude the vessel lumen. In vitro experiment found that vessel constriction was due to the constriction of thrombus induced by laser irradiation. Theoretical investigation revealed that the mechanism for the effective reduction of energy density by multi-pulse Nd:YAG laser was due to enhanced light absorption of the blood with thrombus formation. For multi-pulse treatment, laser

  12. 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.

  13. Could MRI visualize the invisible? An Italian single center study comparing magnetic resonance lymphography (MRL), super microsurgery and histology in the identification of lymphatic vessels.

    Science.gov (United States)

    Gennaro, P; Borghini, A; Chisci, G; Mazzei, F G; Weber, E; Tedone Clemente, E; Guerrini, S; Gentili, F; Gabriele, G; Ungari, C; Mazzei, M A

    2017-02-01

    Aim of this study is to evaluate the possibility of limb magnetic resonance lymphography (MRL) to differentiate lymphatic vessels from pathological veins, collect a specimen of the identified lymphatic vessel during operations of super microsurgical lymphatic-venular anastomosis (s-LVA) and perform immunohistochemical stainings to confirm the nature of the collected vessels. Twenty patients presenting lymphedema were enrolled in this study. Five patients reported lower limb lymphedema and 15 patients reported upper limb lymphedema. All patients had the indication for s-LVA and underwent preoperative MRL imaging of the affected limb. A total of 57 lymphatic vessels were identified by MRL and used to guide s-LVA: all these vessels have also been used to perform an intraoperative biopsy for immunohistochemical evaluation. A total of 53/57 vascular structures resulted compatible with lymphatic vessels at the immunohistochemical study performed with D2-40 antibody; 3/57 specimen showed the absence of the D2-40 antibody. A significant association was found between preoperative MRL and immunohistochemical marker D2-40 on collected specimen. Most of the articles in the international literature report the concomitant presence of both lymphatic and venous vessels at MRL. However, no one in literature describes the possibility to differentiate venous vessels from lymphatic vessels, and this is a crucial issue for the correct evaluation of the lymphatic system in patients with limb lymphedema undergoing a future surgical correction. In the present study, MRL allowed to identify active lymphatic vessels. MRL was predictive to determine preoperatory lymphatic vessels and to perform successful s-LVA in lymphedema patients. This is the first study to prove the nature of the vessels identified at the preoperative MRL with immunohistochemical stainings.

  14. Lymphatic mapping and lymphedema surgery in the breast cancer patient

    Science.gov (United States)

    Manrique, Oscar; Sosin, Michael; Hashmi, Mahjabeen Aftab; Poysophon, Poysophon; Henderson, Robert

    2015-01-01

    Upper limb lymphedema can be an unfortunate sequela following the oncologic treatment of breast cancer. The surgical treatment of lymphedema has had a recent renewed clinical interest paralleling innovative descriptions of surgical techniques and imaging modalities. In addition, an improved understanding of the physiology and pathophysiology of lymphedema has allowed improved translation to the clinical condition. Various surgical options exist to decrease the symptom-burden of upper limb lymphedema, including vascularized lymph node (VLN) transfer, lymphovenous bypass (LVB), liposuction, lymphatic grafting, and excisional procedures. Modern imaging techniques help to improve the consistency and accuracy of these surgical treatment options. A multi-modal treatment plan utilizing non-operative and surgical therapies has the potential to improve various factors related to overall patient quality of life. This review details all of the current operative treatment strategies and modern imaging modalities used in the treatment of lymphedema. PMID:26161309

  15. Lymphatic endothelial cancerization in papillary thyroid carcinoma: hidden evidence of lymphatic invasion.

    Science.gov (United States)

    Mai, Kien T; Truong, Luan D; Ball, Christopher G; Olberg, Bernhard; Lai, Chi K; Purgina, Bibianna

    2015-05-01

    We hypothesize that cystic structures in metastatic papillary thyroid carcinoma (PTC) develop along the framework of lymphatic channels. To investigate this phenomenon, different categories of PTC were immunostained for D2-40 and TTF1. In this study, reactivity for D2-40 was considered as positive when there is membranous staining as often seen in lymphatic endothelial cells. Thirty cases of PTC with lymph node metastasis or with potential for lymphatic invasion and 20 cases metastatic PTC in lymph nodes were reviewed and found to show double/mosaic immunoreactivity for TTF1/D2-40 in 40-100% of cases. PTC metastasis in lymph nodes with cysts and some branching lymphatic-like channels lined by follicular cells with or without nuclear features of PTC were diffusely reactive to TTF1, and focally to D2-40. For primary and metastatic PTC, focal membranous D2-40 reactivity was also demonstrated in cysts or cleft linings. For25 thyroid neoplasms with no known potential for lymphatic invasion, there was no such immunoreactivity. The mosaic or double immunoreactivity for TTF1/D2-40 suggests lymphatic cancerization and possible endothelial mimicry of follicular cells. Mosaic/double immunoreactivity is helpful to detect the hidden pattern of lymphatic invasion masquerading as 'benign-appearing' follicles and supports our hypothesis of malignant cells developing along the lymphatic framework. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  16. Human brain arteriovenous malformations express lymphatic-associated genes.

    Science.gov (United States)

    Shoemaker, Lorelei D; Fuentes, Laurel F; Santiago, Shauna M; Allen, Breanna M; Cook, Douglas J; Steinberg, Gary K; Chang, Steven D

    2014-12-01

    Brain arteriovenous malformations (AVMs) are devastating, hemorrhage-prone, cerebrovascular lesions characterized by well-defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs) that comprise AVMs exhibit a loss of arterial and venous specification. Given the role of the transcription factor COUP-TFII in vascular development, EC specification, and pathological angiogenesis, we examined human AVM tissue to determine if COUP-FTII may have a role in AVM disease biology. We examined 40 human brain AVMs by immunohistochemistry (IHC) and qRT-PCR for the expression of COUP-TFII as well as other genes involved in venous and lymphatic development, maintenance, and signaling. We also examined proliferation and EC tube formation with human umbilical ECs (HUVEC) following COUP-TFII overexpression. We report that AVMs expressed COUP-TFII, SOX18, PROX1, NFATC1, FOXC2, TBX1, LYVE1, Podoplanin, and vascular endothelial growth factor (VEGF)-C, contained Ki67-positive cells and heterogeneously expressed genes involved in Hedgehog, Notch, Wnt, and VEGF signaling pathways. Overexpression of COUP-TFII alone in vitro resulted in increased EC proliferation and dilated tubes in an EC tube formation assay in HUVEC. This suggests AVM ECs are further losing their arterial/venous specificity and acquiring a partial lymphatic molecular phenotype. There was significant correlation of gene expression with presence of clinical edema and acute hemorrhage. While the precise role of these genes in the formation, stabilization, growth and risk of hemorrhage of AVMs remains unclear, these findings have potentially important implications for patient management and treatment choice, and opens new avenues for future work on AVM disease mechanisms.

  17. Lymphatic Vascularisation and Involvement of Lyve-1+ Macrophages in the Human Onchocerca Nodule

    Science.gov (United States)

    Attout, Tarik; Hoerauf, Achim; Dénécé, Gaëlle; Debrah, Alexander Yaw; Marfo-Debrekyei, Yeboah; Boussinesq, Michel; Wanji, Samuel; Martinez, Valérie; Mand, Sabine; Adjei, Ohene; Bain, Odile

    2009-01-01

    Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e.g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses. PMID:20011036

  18. Superficial lymphatic drainage of the lower extremity: anatomical study and clinical implications.

    Science.gov (United States)

    Pan, Wei-Ren; Wang, De-Guang; Levy, Sidney M; Chen, Yuan

    2013-09-01

    Knowledge of the lymphatic anatomy in the lower extremity is inadequate. A reevaluation is needed to assist in guiding clinical management. A total of five lower extremities from three unembalmed human cadavers were studied. Under a surgical microscope, 6% hydrogen peroxide was used to detect the lymphatic vessels commencing from the foot, the leg, and the thigh. A 30-gauge needle was inserted into the vessels and injected with a radiopaque lead oxide mixture. The vessels were traced, photographed, and radiographed to demonstrate the superficial lymphatic pathways of the lower extremity. The final results were transferred to the computer for image analysis. Numerous lymph collecting vessels were identified in the subcutaneous tissue and the superficial femoral vascular bundle of the lower extremity. They originated beneath the dermis of each side of the toes, the foot, and the lateral side of the thigh. The diameters of the vessels varied from 0.2 to 2.2 mm. The vessels traveled in the subcutaneous tissue of the lower limb toward the popliteal, femoral, superficial, and deep inguinal lymph nodes. During their tortuous course, some vessels branched, diverged, and converged; sometimes, they anastomosed with neighboring vessels or crossed them. Most vessels converged to form larger collectors and then diverged into small branches before entering the lymph nodes. Accurate lymphatic distribution within the lower extremity has been described. This information upgrades our anatomical knowledge, and the results will be of benefit for clinical management.

  19. VASCULAR DEMENTIA

    Directory of Open Access Journals (Sweden)

    Maria Alekseyevna Cherdak

    2010-01-01

    vascular cognitive disorders and vascular dementia (VD. The heterogeneity of vascular cognitive disorders, concurrence of vascular and neurodegenerative diseases are discussed. Data from studies of specific therapy for VD are given.

  20. HSV-1 targets lymphatic vessels in the eye and draining lymph node of mice leading to edema in the absence of a functional type I interferon response.

    Science.gov (United States)

    Bryant-Hudson, Katie M; Chucair-Elliott, Ana J; Conrady, Christopher D; Cohen, Alex; Zheng, Min; Carr, Daniel J J

    2013-10-01

    Herpes simplex virus type-1 (HSV-1) induces new lymphatic vessel growth (lymphangiogenesis) in the cornea via expression of vascular endothelial growth factor by virally infected epithelial cells. Here, we extend this observation to demonstrate the selective targeting of corneal lymphatics by HSV-1 in the absence of functional type I interferon (IFN) pathway. Specifically, we examined the impact of HSV-1 replication on angiogenesis using type I IFN receptor deficient (CD118(-/-)) mice. HSV-1-induced lymphatic and blood vessel growth into the cornea proper was time-dependent in immunocompetent animals. In contrast, there was an initial robust growth of lymphatic vessels into the cornea of HSV-1-infected CD118(-/-)mice, but such vessels disappeared by day 5 postinfection. The loss was selective as blood vessel integrity remained intact. Magnetic resonance imaging and confocal microscopy analysis of the draining lymph nodes of CD118(-/-) mice revealed extensive edema and loss of lymphatics compared with wild-type mice. In addition to a loss of lymphatic vessels in CD118(-/-) mice, HSV-1 infection resulted in epithelial thinning associated with geographic lesions and edema within the cornea, which is consistent with a loss of lymphatic vasculature. These results underscore the key role functional type I IFN pathway plays in the maintenance of structural integrity within the cornea in addition to the anti-viral characteristics often ascribed to the type I IFN cytokine family. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Effect of pneumatic compression therapy on lymph movement in lymphedema-affected extremities, as assessed by near-infrared fluorescence lymphatic imaging

    Directory of Open Access Journals (Sweden)

    Melissa B. Aldrich

    2017-03-01

    Full Text Available Previous studies have shown cost effectiveness and quality-of-life benefit of pneumatic compression therapy (PCT for lymphedema (LE. Insurers, such as the Centers for Medicare/Medicaid (CMS, however, desire visual proof that PCT moves lymph. Near-infrared fluorescence lymphatic imaging (NIRFLI was used to visualize lymphatic anatomy and function in four subjects with primary and cancer treatment-related LE of the lower extremities before, during, and after PCT. Optically transparent and windowed PCT garments allowed visualization of lymph movement during single, 1h PCT treatment sessions. Visualization revealed significant extravascular and lymphatic vascular movement of intradermally injected dye in all subjects. In one subject with sufficient patent lymphatic vessels to allow quantification of lymph pumping velocities and frequencies, these values were significantly increased during and after PCT as compared to pre-treatment values. Lymphatic contractile activity in patent lymphatic vessels occurred in concert with the sequential cycling of PCT. Direct visualization revealed increased lymphatic function, during and after PCT therapy, in all LE-affected extremities. Further studies are warranted to assess the effects of PCT pressure and sequences on lymph uptake and movement.

  2. Noninvasive vascular ultrasound elastography applied to the characterization of experimental aneurysms and follow-up after endovascular repair

    Energy Technology Data Exchange (ETDEWEB)

    Fromageau, Jeremie; Maurice, Roch Listz; Cloutier, Guy [Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center (CRCHUM), Montreal, Quebec, H2L 2W5 (Canada); Lerouge, Sophie [Laboratory of Endovascular Biomaterials, University of Montreal Hospital Research Center (CRCHUM), Montreal, Quebec, H2L 2W5 (Canada) and Department of Mechanical Engineering, Ecole de Technologie Superieure, Montreal, Quebec, H3C 1K3 (Canada); Soulez, Gilles [Department of Radiology, University of Montreal Hospital, Montreal, Quebec, H2L 4M1 (Canada)], E-mail: guy.cloutier@umontreal.ca

    2008-11-21

    Experimental and simulation studies were conducted to noninvasively characterize abdominal aneurysms with ultrasound (US) elastography before and after endovascular treatment. Twenty three dogs having bilateral aneurysms surgically created on iliac arteries with venous patches were investigated. In a first set of experiments, the feasibility of elastography to differentiate vascular wall elastic properties between the aneurismal neck (healthy region) and the venous patch (pathological region) was evaluated on six dogs. Lower strain values were found in venous patches (p < 0.001). In a second set of experiments, 17 dogs having endovascular repair (EVAR) by stent graft (SG) insertion were examined three months after SG implantation. Angiography, color Doppler US, examination of macroscopic sections and US elastography were used. The value of elastography was validated with the following end points by considering a solid thrombus of a healed aneurysm as a structure with small deformations and a soft thrombus associated with endoleaks as a more deformable tissue: (1) the correlation between the size of healed organized thrombi estimated by elastography and by macroscopic examinations; (2) the correlation between the strain amplitude measured within vessel wall elastograms and the leak size; and (3) agreement on the presence and size of endoleaks as determined by elastography and by combined reference imaging modalities (angiography + Doppler US). Mean surfaces of solid thrombi estimated with elastography were found correlated with those measured on macroscopic sections (r = 0.88, p < 0.001). Quantitative strain values measured within the vessel wall were poorly linked with the leak size (r = 0.12, p = 0.5). However, the qualitative evaluation of leak size in the aneurismal sac was very good, with a Kappa agreement coefficient of 0.79 between elastography and combined reference imaging modalities. In summary, complementing B-scan and color Doppler, noninvasive US

  3. Total fraction of mononuclear cell or stromal vascular fraction transplant associated with cellulosic membrane in experimental cutaneous wounds in rabbits

    Directory of Open Access Journals (Sweden)

    Tiago Luis Eilers Treichel

    2011-02-01

    Full Text Available A pele apresenta diversas funções importantes para o organismo. A manutenção de sua integridade é fundamental, entre outras, para impedir a penetração de microrganismos e a perda de líquidos essenciais à manutenção da vida. Por estar constantemente exposta ao meio ambiente, a pele é altamente susceptível a traumas que podem acarretar soluções de continuidade. A cicatrização da pele ferida deve ser rápida e diversas alternativas são buscadas, visando à redução do tempo de reparo a fim de garantir cicatriz funcional e esteticamente aceitável. Uma opção cada vez mais viável para reparar tecidos danificados é a terapia celular com células-tronco adultas. Os objetivos deste trabalho consistiram em avaliar o transplante da fração total de células mononucleares (FTCM da medula óssea (MO e da fração vascular estromal (FVE do tecido adiposo (TA, associado ao uso da membrana celulósica. Para realização deste experimento, 20 coelhos foram divididos aleatoriamente em quatro grupos com cinco animais cada. Após a indução da ferida cutânea experimental, o grupo A, não recebeu nenhum tratamento, o grupo B, recebeu apenas membrana celulósica e os grupos C e D, além de receberem a membrana, foram submetidos a transplante autólogo da FTCM, com valor total de células entre 6,92 x 10(6 a 4,91 x 10(7 e uma viabilidade de 82 a 97% ou da FVE, com valor total de células entre 9,6 x 10(5 e 6,5 x 10(6 e uma viabilidade de 66 a 87%, respectivamente. Ao final do período de avaliação, os três grupos tratados apresentaram diferença estatística significativa da área da ferida em relação ao grupo controle e o grupo que recebeu a FVE do tecido adiposo apresentou o menor tempo de cicatrização da ferida.

  4. 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.

  5. Lamb congenital lymphatic malformation - a case report

    Directory of Open Access Journals (Sweden)

    Neria Santos

    2014-01-01

    Full Text Available Lymphatic malformations have been rarely reported in literature either in humans or in animals. However, in recent years, concern about these malformations in humans has increased. A five-month-old Rasa Aragonesa male lamb was received at the Ovine Clinical Service of the Veterinary Faculty of Zaragoza, Spain, with a history of cervical protuberances coming from birth. The lamb showed three round swollen lumps (5–12 cm in diameter parallel to the trachea on the left side of the neck. Clinical examination, haematology, ultrasonography, fluid examination and histopathology were performed. No abnormalities were found in blood samples and ultrasound confirmed a multicystic lesion with internal separations. Histological evaluation of the tissue revealed dilated lymphatic vessels and channels in the dermis and hypodermis; some lymphatic vessels were filled with amorphous proteinaceous material and occasional lymphocytes and macrophages. These protuberances were diagnosed as congenital lymphatic malformations. Most of the gross and microscopical lesions were very similar to those described in humans. To the authors’ knowledge, this is the first time that a congenital lymphatic malformation is described in sheep.

  6. Lymphatic Vessels: The Next Frontier in Lung Transplant.

    Science.gov (United States)

    Cui, Ye; Liu, Kaifeng; Lamattina, Anthony Mark; Visner, Gary; El-Chemaly, Souheil

    2017-09-01

    Lymphatic vessels are essential for the uptake of fluid, immune cells, macromolecules, and lipids from the interstitial space. During lung transplant surgery, the pulmonary lymphatic vessel continuum is completely disrupted, and, as a result, lymphatic drainage function is severely compromised. After transplantation, the regeneration of an effective lymphatic drainage system plays a crucial role in maintaining interstitial fluid balance in the lung allograft. In the meantime, these newly formed lymphatic vessels are commonly held responsible for the development of immune responses leading to graft rejection, because they are potentially capable of transporting antigen-presenting cells loaded with allogeneic antigens to the draining lymph nodes. However, despite remarkable progress in the understanding of lymphatic biology, there is still a paucity of consistent evidence that demonstrates the exact impacts of lymphatic vessels on lung graft function. In this review, we examine the current literature related to roles of lymphatic vessels in the pathogenesis of lung transplant rejection.

  7. Interaction between the extracellular matrix and lymphatics - consequences for lymphangiogenesis and lymphatic function

    Science.gov (United States)

    Wiig, Helge; Keskin, Doruk; Kalluri, Raghu

    2014-01-01

    The lymphatic system is important for body fluid balance as well as immunological surveillance. Due to the identification of new molecular markers during the last decade, there has been a recent dramatic increase in our knowledge on the molecular mechanisms involved in lymphatic vessel growth (lymphangiogenesis) and lymphatic function. Here we review data showing that although it is often overlooked, the extracellular matrix plays an important role in the generation of new lymphatic vessels as a response to physiological and pathological stimuli. Extracellular matrix-lymphatic interactions as well as biophysical characteristics of the stroma have consequences for tumor formation, growth and metastasis. During the recent years, anti-lymphangiogenesis has emerged as an additional therapeutic modality to the clinically applied anti-angiogenesis strategy. Oppositely, enhancement of lymphangiogenesis in situations of lymph accumulation is seen as a promising strategy to a set of conditions where few therapeutic avenues are available. Knowledge on the interaction between the extracellular matrix and the lymphatics may enhance our understanding of the underlying mechanisms and may ultimately lead to better therapies for conditions where reduced or increased lymphatic function is the therapeutic target PMID:20727409

  8. Multiscale modeling of lymphatic drainage from tissues using homogenization theory

    OpenAIRE

    Roose Tiina; Swartz Melody A.

    2012-01-01

    Lymphatic capillary drainage of interstitial fluid under both steady state and inflammatory conditions is important for tissue fluid balance cancer metastasis and immunity. Lymphatic drainage function is critically coupled to the fluid mechanical properties of the interstitium yet this coupling is poorly understood. Here we sought to effectively model the lymphatic interstitial fluid coupling and ask why the lymphatic capillary network often appears with roughly a hexagonal architecture. We u...

  9. Nonimmune idiopathic hydrops fetalis and congenital lymphatic dysplasia

    NARCIS (Netherlands)

    Bellini, Carlo; Hennekam, Raoul C. M.; Boccardo, Francesco; Campisi, Corradino; Serra, Giovanni; Bonioli, Eugenio

    2006-01-01

    Six newborns that presented at birth with nonimmune hydrops fetalis and for whom no cause could be found were investigated for the presence of lymphatic dysplasia. Careful analysis led to findings of some degree of lymphatic dysplasia in all patients. This suggests that lymphatic dysplasia may

  10. Pitfalls in Cutaneous Melanoma Lymphatic Drainage.

    Science.gov (United States)

    Voinea, Silviu; Sandru, Angela; Gherghe, Mirela

    2016-01-01

    Sentinel node (SN) biopsy has become standard in staging of cutaneous melanoma. As skin lymphatic drainage is complex, preoperative empirical assessment of SN localization is virtually impossible. Therefore in order to identify all regional lymphatic basins corresponding to a specific primary tumor is mandatory to carry out preoperative lymphoscintigraphy. In this paper we present a clinical case that highlights the importance of identifying, biopsy and histological analysis of all SN in order to achieve a correct staging of the patient, followed by appropriate treatment according to the real clinical stage of the disease. Celsius.

  11. VIPAR, a quantitative approach to 3D histopathology applied to lymphatic malformations.

    Science.gov (United States)

    Hägerling, René; Drees, Dominik; Scherzinger, Aaron; Dierkes, Cathrin; Martin-Almedina, Silvia; Butz, Stefan; Gordon, Kristiana; Schäfers, Michael; Hinrichs, Klaus; Ostergaard, Pia; Vestweber, Dietmar; Goerge, Tobias; Mansour, Sahar; Jiang, Xiaoyi; Mortimer, Peter S; Kiefer, Friedemann

    2017-08-17

    Lack of investigatory and diagnostic tools has been a major contributing factor to the failure to mechanistically understand lymphedema and other lymphatic disorders in order to develop effective drug and surgical therapies. One difficulty has been understanding the true changes in lymph vessel pathology from standard 2D tissue sections. VIPAR (volume information-based histopathological analysis by 3D reconstruction and data extraction), a light-sheet microscopy-based approach for the analysis of tissue biopsies, is based on digital reconstruction and visualization of microscopic image stacks. VIPAR allows semiautomated segmentation of the vasculature and subsequent nonbiased extraction of characteristic vessel shape and connectivity parameters. We applied VIPAR to analyze biopsies from healthy lymphedematous and lymphangiomatous skin. Digital 3D reconstruction provided a directly visually interpretable, comprehensive representation of the lymphatic and blood vessels in the analyzed tissue volumes. The most conspicuous features were disrupted lymphatic vessels in lymphedematous skin and a hyperplasia (4.36-fold lymphatic vessel volume increase) in the lymphangiomatous skin. Both abnormalities were detected by the connectivity analysis based on extracted vessel shape and structure data. The quantitative evaluation of extracted data revealed a significant reduction of lymphatic segment length (51.3% and 54.2%) and straightness (89.2% and 83.7%) for lymphedematous and lymphangiomatous skin, respectively. Blood vessel length was significantly increased in the lymphangiomatous sample (239.3%). VIPAR is a volume-based tissue reconstruction data extraction and analysis approach that successfully distinguished healthy from lymphedematous and lymphangiomatous skin. Its application is not limited to the vascular systems or skin. Max Planck Society, DFG (SFB 656), and Cells-in-Motion Cluster of Excellence EXC 1003.

  12. 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.

  13. An investigation of the topography of the lymphatic system of the grey kangaroo (Macropus giganteus). 1. The superficial lymphatic system.

    OpenAIRE

    Hopwood, P R

    1988-01-01

    The superficial lymphatic system of the grey kangaroo, Macropus giganteus is described. The description is based on dissections of 130 eastern grey kangaroos. The most significant difference found between the superficial lymphatic drainage pattern of kangaroos and that of the domestic species was the existence of large inguino-axillary lymphatic trunks in the kangaroo. Thus in the kangaroo, instead of lymph passing from the inguinal lymphocentre to the lumbar lymphatic trunks as is the situat...

  14. 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.

  15. Visualization of experimental glioma C6 by MRI with magnetic nanoparticles conjugated with monoclonal antibodies to vascular endothelial growth factor.

    Science.gov (United States)

    Abakumov, M A; Shein, S A; Vishvasrao, H; Nukolova, N V; Sokol'ski-Papkov, M; Sandalova, T O; Gubskii, I L; Grinenko, N F; Kabanov, A V; Chekhonin, V P

    2012-12-01

    We developed a method for obtaining iron oxide nanoparticles and their conjugation with monoclonal antibodies to vascular endothelial growth factor. The resultant vector nanoparticles were low-toxic and the antibodies retained their immunochemical activity after conjugation. The study was carried out on rats with intracranial glioma C6 on day 14 after its implantation. The intravenously injected nanoparticles visualized the brain tumor in contrast to nanoparticles conjugated with nonspecific immunoglobulins that did not accumulate in the tumor.

  16. Neuroprotective and memory enhancing effects of auraptene in a rat model of vascular dementia: Experimental study and histopathological evaluation.

    Science.gov (United States)

    Ghanbarabadi, Mustafa; Iranshahi, Mehrdad; Amoueian, Sakineh; Mehri, Soghra; Motamedshariaty, Vahideh Sadat; Mohajeri, Seyed Ahmad

    2016-06-03

    Vascular dementia and Alzheimer disease are most common type of dementia. These diseases have been associated with cognitive decline and affected personal behavioral activities. Moreover, the pattern of cerebral blood flow in mild cognitive disorder has appeared as a predictive indication for the development into Alzheimer's disease. Permanent, bilateral occlusion of the common carotid arteries (2VO) is a standard animal model to study vascular dementia and chronic cerebral hypoperfusion. In present study neuroprotective and memory enhancing effects of auraptene (AUR), a citrus coumarin, were studied in 2VO rats. Different doses (25, 8 & 4mg/kg) of AUR were administered orally. The spatial memory performance was tested with Morris water maze after 2VO induction. Biochemical experiments and histopathological evaluations were also applied to investigate the neuroprotective effect of AUR in brain tissue. In comparison with 2VO group, AUR could significantly decrease the scape latency time in treated rats. Also AUR increased the percentage of time spent and traveled pathway in target quadrant on final trial test day. All behavioral results were confirmed by biochemical and histopathological data. Biochemical data indicated that AUR could decrease malondialdehyde (MDA), as lipid peroxidation indicator, and increase glutathione (GSH) content in cortex and hippocampus tissues. Histopathological data showed that AUR could protect cerebrocortical and hippocampus neurons against ischemia. This study demonstrated the memory enhancing effect and neuroprotective activity of AUR after induction of brain ischemia in a rat model of vascular dementia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Lymphatic muscle cells in rat mesenteric lymphatic vessels of various ages.

    Science.gov (United States)

    Bridenbaugh, Eric A; Nizamutdinova, Irina Tsoy; Jupiter, Daniel; Nagai, Takashi; Thangaswamy, Sangeetha; Chatterjee, Victor; Gashev, Anatoliy A

    2013-03-01

    Recent studies on aging-associated changes in mesenteric lymph flow in situ demonstrated predominance of the severe negative chronotropic effect of aging on the contractility of aged mesenteric lymphatic vessels (MLV). At the same time, contraction amplitude of the aged vessels was only slightly diminished by aging and can be rapidly stimulated within 5-15 minutes. However, the detailed quantitative evaluation of potential aging-associated changes in muscle cells investiture in MLV has never been performed. In this study we, for the first time, performed detailed evaluation of muscle cells investiture in MLV in reference to the position of lymphatic valve in different zones of lymphangion within various age groups (3-mo, 9-mo and 24-mo Fischer-344 rats). Using visual and quantitative analyses of the images of MLV immunohistochemically labeled for actin, we confirmed that the zones located close upstream (pre-valve zones) and above lymphatic valves (valve zones) possess the lowest investiture of lymphatic muscle cells. Most of the high muscle cells investiture zones exist downstream to the lymphatic valve (post-valve zones). The muscle cells investiture of these zones is not affected by aging, while pre-valve and valve zones demonstrate significant aging-associated decrease in muscle cells investiture. The low muscle cells investiture zones in lymphatic vessels consist of predominantly longitudinally oriented muscle cells which are positioned in pre-valve and valve zones and connect adjacent lymphangions. These cells may provide important functional impact on the biomechanics of the lymphatic valve gating and electrical coupling between lymphangions, while their aging-associated changes may delimit adaptive reserves of aged lymphatic vessels.

  18. Propranolol as an alternative treatment option for pediatric lymphatic malformation.

    Science.gov (United States)

    Ozeki, Michio; Kanda, Kaori; Kawamoto, Norio; Ohnishi, Hidenori; Fujino, Akihiro; Hirayama, Masahiro; Kato, Zenichiro; Azuma, Eiichi; Fukao, Toshiyuki; Kondo, Naomi

    2013-01-01

    Lymphatic malformation (LM), which was previously termed lymphangioma, is a rare congenital malformation of the lymphatic system and its treatment is still challenging. Propranolol (beta blocker) has been recently developed as a first-line treatment of infantile hemangioma. Our study aimed to assess the effect of propranolol on pediatric LM and the relationship between its effectiveness and vascular endothelial growth factor (VEGF) family members (VEGF-A, C and D). Six Japanese patients with LM (age range: 10 months-19 years old; 2 macrocystic, 2 microcystic and 2 combined type) were enrolled. Oral propranolol was administered at 2 mg/kg/day. The efficacy of propranolol for LM was evaluated by the rate of volume change as calculated from MRI imaging and by symptomatic improvement. In all patients, there were no significant side effects. Patients 3 and 5 were classified as objective responders with tumor volume reduction of 30.6% and 22.9%, respectively, at 24 weeks. Patient 1 showed 8% tumor volume reduction and patient 6 showed symptomatic improvement, hence, both were classified as minimal responders. The other two patients were classified as non-responders. Plasma VEGF-A, C, and D levels were significantly higher in the LM group than in the controls (all P < 0.01 by Mann-Whitney test). VEGF-A and D levels at 24 weeks were significantly lower than those at pre-treatment (P = 0.031, 0.047 by Wilcoxon matched pairs test). Though further trials with this treatment must be carried out, we propose that propranolol may be an alternative therapy option for intractable LM.

  19. 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.

  20. Sentinel surveillance of Lymphatic filariasis, Schistosomiasis, Soil ...

    African Journals Online (AJOL)

    Background: Baseline prevalence and knowledge, attitude and perception (KAP) survey is a prerequisite for mass drug administration for the control of Lymphatic filariasis (LF) and other neglected tropical diseases. Methods: In preparation for the first mass drug administration for LF elimination, a baseline survey was ...

  1. Immunopathogenesis of lymphatic filarial disease1

    Science.gov (United States)

    Babu, Subash; Nutman, Thomas B.

    2012-01-01

    Although two-thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ~ 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process - the first initiated by the parasite and host innate immune system and the second propagated mainly by the host’s adaptive immune system and by other factors (including secondary infections). PMID:23053393

  2. 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,

  3. Prevalence of lymphatic complications due to onchocerciasis ...

    African Journals Online (AJOL)

    The study was conducted to determine the prevalence of lymphatic complications due to onchocerciasis infection in 38 endemic rural communities in the Imo River Basin, Nigeria. Using standard parasitological and clinical methods of diagnosis, 7,144 consenting individuals aged 5 years and above were examined for ...

  4. Ivermectin-Albendazole Combination Therapy in Lymphatic ...

    African Journals Online (AJOL)

    The commonest manifestation of lymphatic filariasis is lymphoedema, which on progression leads on to elephantiasis. Even though lower limbs are commonly affected, upper limbs involvement is rarely reported in West Africa especially in females. In the present report a 19 year old female (BMI 20.49 kg/m2) in the ...

  5. Preliminary studies on human lymphatic filariasis transmission ...

    African Journals Online (AJOL)

    Preliminary studies on human lymphatic filariasis transmission control trials using Insecticide Treated Bednet (ITBN) in parts of Imo State, Nigeria. ... Two cohorts were used; ITBN-full coverage/wide scale use and ITBN-vulnerable coverage/ selective use. Endophilic mosquitoes caught twice a month by pyrethrum spray ...

  6. Embryonic development and malformation of lymphatic vessels.

    Science.gov (United States)

    Wilting, Jörg; Buttler, Kerstin; Rössler, Jochen; Norgall, Susanne; Schweigerer, Lothar; Weich, Herbert A; Papoutsi, Maria

    2007-01-01

    In the human, malformations of lymphatic vessels can be observed as lymphangiectasia, lymphangioma and lymphangiomatosis, with a prevalence of 1.2-2.8 per thousand. Their aetiology is unknown and a causal therapy does not exist. We investigated the origin of lymphatic endothelial cells (LECs) in avian and murine embryos, and compared the molecular profile of LECs from normal and malformed lymphatics of children. In avian embryos, Prox1+ lymphangioblasts are located in the confluence of the cranial and caudal cardinal veins, where the jugular lymph sac (JLS) forms. Cell lineage studies show that the JLS is of venous origin. In contrast, the lymphatics of the dermis are derived from mesenchymal lymphangioblasts located in the dermatomes, suggesting a dual origin of LECs in avian embryos. The same may hold true for murine embryos, where Lyve1+ LEC precursors are found in the cardinal veins, and in the mesenchyme. The mesenchymal cells express the pan-leukocyte marker CD45, indicating a cell type with lymphendothelial and leukocyte characteristics. In the human, such cells might give rise to Kaposi's sarcoma. Microarray analyses of LECs from lymphangiomas of children show a large number of regulated genes, such as VEGFR3. Our studies show that lymphvasculogenesis and lymphangiogenesis occur simultaneously in the embryo, and suggest a function for VEGFR3 in lymphangiomas.

  7. 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...

  8. Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic drainage.

    Science.gov (United States)

    Iolyeva, Maria; Aebischer, David; Proulx, Steven T; Willrodt, Ann-Helen; Ecoiffier, Tatiana; Häner, Simone; Bouchaud, Grégory; Krieg, Carsten; Onder, Lucas; Ludewig, Burkhard; Santambrogio, Laura; Boyman, Onur; Chen, Lu; Finke, Daniela; Halin, Cornelia

    2013-09-26

    The cytokine interleukin (IL)-7 exerts essential roles in lymph node (LN) organogenesis and lymphocyte development and homeostasis. Recent studies have identified lymphatic endothelial cells (LECs) as a major source of IL-7 in LNs. Here, we report that LECs not only produce IL-7, but also express the IL-7 receptor chains IL-7Rα and CD132. Stimulation with recombinant IL-7 enhanced LEC in vitro activity and induced lymphangiogenesis in the cornea of wild-type (WT) mice. Whereas in IL-7Rα(-/-) mice, dermal lymphatic vessels (LVs) were abnormally organized and lymphatic drainage was compromised, transgenic overexpression of IL-7 in mice resulted in an expanded dermal LV network with increased drainage function. Moreover, systemic treatment with recombinant IL-7 enhanced lymphatic drainage in the skin of WT mice and of mice devoid of lymphocytes. Experiments in IL-7Rα(-/-) bone marrow chimeras demonstrated that the drainage-enhancing activity of IL-7 was exclusively dependent on IL-7Rα expression in stromal but not in hematopoietic cells. Finally, near-infrared in vivo imaging performed in IL-7Rα(-/-) mice revealed that the pumping activity of collecting vessels was normal but fluid uptake into lymphatic capillaries was defective. Overall, our data point toward an unexpected new role for IL-7 as a potential autocrine mediator of lymphatic drainage.

  9. Multiscale modeling of lymphatic drainage from tissues using homogenization theory.

    Science.gov (United States)

    Roose, Tiina; Swartz, Melody A

    2012-01-03

    Lymphatic capillary drainage of interstitial fluid under both steady-state and inflammatory conditions is important for tissue fluid balance, cancer metastasis, and immunity. Lymphatic drainage function is critically coupled to the fluid mechanical properties of the interstitium, yet this coupling is poorly understood. Here we sought to effectively model the lymphatic-interstitial fluid coupling and ask why the lymphatic capillary network often appears with roughly a hexagonal architecture. We use homogenization method, which allows tissue-scale lymph flow to be integrated with the microstructural details of the lymphatic capillaries, thus gaining insight into the functionality of lymphatic anatomy. We first describe flow in lymphatic capillaries using the Navier-Stokes equations and flow through the interstitium using Darcy's law. We then use multiscale homogenization to derive macroscale equations describing lymphatic drainage, with the mouse tail skin as a basis. We find that the limiting resistance for fluid drainage is that from the interstitium into the capillaries rather than within the capillaries. We also find that between hexagonal, square, and parallel tube configurations of lymphatic capillary networks, the hexagonal structure is the most efficient architecture for coupled interstitial and capillary fluid transport; that is, it clears the most interstitial fluid for a given network density and baseline interstitial fluid pressure. Thus, using homogenization theory, one can assess how vessel microstructure influences the macroscale fluid drainage by the lymphatics and demonstrate why the hexagonal network of dermal lymphatic capillaries is optimal for interstitial tissue fluid clearance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Compression therapy for congenital low-flow vascular malformations of the extremities: A systematic review

    NARCIS (Netherlands)

    Langbroek, Ginger B.; Horbach, Sophie E. R.; van der Vleuten, Carine J. M.; Ubbink, Dirk T.; van der Horst, Chantal M. A. M.

    2018-01-01

    Introduction Low-flow vascular malformations are congenital abnormalities of the veins, capillaries or lymphatic vessels or a combination of the previous. Compressive garments are frequently used as a first-line treatment option for low-flow vascular malformations of the extremities with the purpose

  11. Intraoperative navigation in robotically assisted compartmental surgery of uterine cancer by visualisation of embryologically derived lymphatic networks with indocyanine-green (ICG).

    Science.gov (United States)

    Kimmig, Rainer; Aktas, Bahriye; Buderath, Paul; Rusch, Peter; Heubner, Martin

    2016-04-01

    To evaluate feasibility of intraoperative visualization of embryologically defined organ compartments and their drainage by ICG in uterine cancer. Total of 2.5 mg of ICG have been injected into cervix or corpus in uterine cancer patients immediately prior to surgery. Green fluorescence was intermittently detected during robotically assisted laparoscopic surgery (Firefly System®, Intuitve Surgical Inc.). Total of 36 patients with uterine cancer without macroscopically suspicious nodes were evaluated with respect to their compartmental lymphatic network, collecting lymphatic vessels, and the connection to the postponed lymph basins. Müllerian (sub) compartment and transport of lymph fluid along the lymphatic collectors and connecting vessels to the postponed lymph basins could be visualized invariably in all patients. Cervix drained along the ligamentous and caudal part of vascular mesometria, whereas midcorporal and fundal drainage occurred along the upper part of vascular mesometria and along the mesonephric pathway along the ovarian vessels. Visualization of lymphatic network and downstream flow of lymphatic fluid to the postponed lymph basins by ICG is feasible; it can be used to navigate along compartment boarders for education, intraoperative orientation, and quality control. It seems to confirm the compartmental order of pelvic organ systems and postponed lymph basins. J. Surg. Oncol. 2016;113:554-559. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Mesenchymal status of lymphatic endothelial cell: enlightening treatment of lymphatic malformation.

    Science.gov (United States)

    Cai, Xu; Zhang, Wei; Chen, Gang; Li, Rui-Fang; Sun, Yan-Fang; Zhao, Yi-Fang

    2015-01-01

    In contrast to blood capillaries, lymphatic capillaries in peripheral tissues are composed of a single-cell layer of lymphatic endothelial cells (LECs) without a covering of mural cells. However, in lymphatic malformations, the enlarged lymphatic vessels were covered with mural cells. This study aimed to understand the molecular mechanism of differences between human dermal lymphatic endothelial cells (HDLECs) and human umbilical vein endothelial cells (HUVECs) and to determine the changes of LECs in the pathological condition of lymphatic malformation. Results showed that HDLECs exhibited lower expression of endothelial proteins, including VE-cadherin and CD31, than HUVECs; HDLECs also showed higher expression of mesenchymal proteins, including α-SMA, SM22α, calponin, and epithelial mesenchymal transition-related transcription factor Slug, than HUVECs. Likewise, HDLECs displayed higher permeability and weaker recruitment of SMCs than HUVECs; HDLECs also exhibited low PDGF-BB expression. TGF-β2 treatment and FGF2 depletion enhanced mesenchymal marker expression with increased permeability and reduced SMC recruitment. By contrast, Slug depletion in HDLECs enhanced VE-cadherin expression, inhibited α-SMA expression, decreased permeability, and enhanced PDGF-BB expression. These results suggested that HDLECs were in a mesenchymal status, which contributed to their functions and might determine their identities. Our data also revealed that miR143/145 was implicated in the mesenchymal status of HDLECs. In lymphatic malformations (LMs) treated with OK-432 sclerotherapy, immunohistochemistry results showed that Prox1 expression was reduced and mural cell investment was increased; these results indicated that LECs lost their mesenchymal status after OK-432 treatment was administered. The decreased mesenchymal status of LECs in LMs may induce dilated vessel constriction, which could be the mechanism of OK-432 sclerotherapy.

  13. Nano-sized drug delivery systems for lymphatic delivery.

    Science.gov (United States)

    Cho, Hea-Young; Lee, Yong-Bok

    2014-01-01

    The lymphatic system plays important roles for immune responses, spreading cancer cells or viruses and disseminating infections. Thus, targeting drugs, such as anticancer, immunotherapeutic and lymphoid contrast agents, to both tumors and the lymphatics, has several advantages such as reduced systemic side effects and increased efficacy. For these reasons, much interest has been focused on the nature of the lymphatics and various studies on the lymphatic delivery of drugs have been carried out. Because the lymphatics consist of a single layer endothelium and have higher permeability compared with that of blood capillaries, studies using nano-sized carriers have been performed. Polymeric nanoparticles, liposomes, and lipid-based vehicles have been adopted as lymphatic delivery carriers. This review will focus on the clinical use of such nano-sized carriers that have been developed for imaging and drug delivery to the lymphatic system. Lymphatic delivery of drugs, such as anticancer, immunotherapeutic and lymphoid contrast agents, using nano-sized carriers has much more improved ability compared with that of conventional dosage forms, but it has not shown the specific lymphatic targeting ability yet. Finally, the challenges for the future are suggested in terms of the mechanisms governing the lymphatic delivery of nano-sized carriers.

  14. Comparison of approaches for microscopic imaging of skin lymphatic vessels.

    Science.gov (United States)

    Wu, Xiufeng; Yu, Zheyuan; Liu, Ningfei

    2012-01-01

    Assessment of skin lymphatic vessels is of great significance in understanding their roles in many pathological conditions. Our aim was to identify the optimal approach for investigation of cutaneous lymphatic system. We performed comparative studies on skin lymphatic vessels using immunohistochemistry of tissue sections, computer graphic reconstruction method together with immunohistochemically stained serial sections and whole mount fluorescence in human lower limb. Lymphatic vessels were identified with podoplanin antibody. The relative merits and drawbacks of each method in evaluation of structure, spatial organization, and distribution of cutaneous lymphatic vessels were described. Immunohistology of tissue sections enabled the investigation of the structure and distribution of the whole cutaneous lymphatic system in two-dimensional slices, whereas three-dimensional morphology of only the most superficial lymph capillary network immediately under the epidermis could be evaluated with the whole mount technique. Meanwhile, only little segmentation of skin lymphatic vessel from five immunohistochemically stained serial sections was reconstructed and evaluated due to expense and special skills required using computer graphic three-dimensional reconstruction. Furthermore, a great number of artifacts and special skills required in its processes leaded to less accurate structure of skin lymphatic vessels. Our findings demonstrated that the use of either of the proposed techniques alone could not allow a comprehensive analysis of the skin lymphatic system due to their relative drawbacks. Combination of immunohistology of tissue sections and three-dimensional whole-mount preparations appears to be the best candidate for comprehensive evaluation of skin lymphatic system. © Wiley Periodicals, Inc.

  15. Lymphatic System: An Active Pathway for Immune Protection

    Science.gov (United States)

    Liao, Shan; von der Weid, Pierre-Yves

    2015-01-01

    Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases. PMID:25534659

  16. Fluorescence imaging of lymphatic outflow of cerebrospinal fluid in mice.

    Science.gov (United States)

    Kwon, Sunkuk; Janssen, Christopher F; Velasquez, Fred Christian; Sevick-Muraca, Eva M

    2017-10-01

    Cerebrospinal fluid (CSF) is known to be reabsorbed by the lymphatic vessels and drain into the lymph nodes (LNs) through peripheral lymphatic vessels. In the peripheral lymphatics, the contractile pumping action of lymphangions mediates lymph drainage; yet it is unknown whether lymphatic vessels draining cranial and spinal CSF show similar function. Herein, we used non-invasive near-infrared fluorescence imaging (NIRFI) to image (i) indocyanine green (ICG) distribution along the neuraxis and (ii) routes of ICG-laden CSF outflow into the lymphatics following intrathecal lumbar administration. We demonstrate lymphatic contractile function in peripheral lymphatics draining from the nasal lymphatics to the mandibular LNs. In addition, we observed afferent sciatic lymphatic vessels, which also show contractile activity and transport spinal CSF into the sciatic LNs. This drainage pattern was also visualized by NIRFI following intrathecal thoracic injection. In situ intravital imaging following intrathecal lumbar injection of blue dye shows similar distributions to that seen in vivo with ICG. NIRFI could be used as a tool to probe CSF pathology including neurological disorders by imaging CSF outflow dynamics to lymphatics. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. ExoU-induced vascular hyperpermeability and platelet activation in the course of experimental Pseudomonas aeruginosa pneumosepsis.

    Science.gov (United States)

    Machado, Gloria-Beatriz S; de Assis, Maria-Cristina; Leão, Robson; Saliba, Alessandra M; Silva, Mauricio C A; Suassuna, Jose H; de Oliveira, Albanita V; Plotkowski, Maria-Cristina

    2010-03-01

    To address the question whether ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, can induce hemostatic abnormalities during the course of pneumosepsis, mice were instilled i.t. with the ExoU-producing PA103 P. aeruginosa or with a mutant obtained by deletion of the exoU gene. Control animals were instilled with sterile vehicle. To assess the role of ExoU in animal survival, mice were evaluated for 72 h. In all the other experiments, animals were studied at 24 h after infection. PA103-infected mice showed significantly higher mortality rate, lower blood leukocyte concentration, and higher platelet concentration and hematocrit than animals infected with the bacterial mutant, as well as evidences of increased vascular permeability and plasma leakage, which were confirmed by our finding of higher protein concentration in bronchoalveolar lavage fluids and by the Evans blue dye assay. Platelets from PA103-infected mice demonstrated features of activation, assessed by the flow cytometric detection of higher percentage of P-selectin expression and of platelet-derived microparticles as well as by the enzyme immunoassay detection of increased thromboxane A2 concentration in animal plasma. Histopathology of lung and kidney sections from PA103-infected mice exhibited evidences of thrombus formation that were not detected in sections of animals from the other groups. Our results demonstrate the ability of ExoU to induce vascular hyperpermeability, platelet activation, and thrombus formation during P. aeruginosa pneumosepsis, and we speculate that this ability may contribute to the reported poor outcome of patients with severe infection by ExoU-producing P. aeruginosa.

  18. Improvement of vascular function by acute and chronic treatment with the GPR30 agonist G1 in experimental diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Zi-lin Li

    Full Text Available The G-protein coupled estrogen receptor 30 (GPR30 is a seven-transmembrane domain receptor that mediates rapid estrogen responses in a wide variety of cell types. This receptor is highly expressed in the cardiovascular system, and exerts vasodilatory effects. The objective of the present study was to investigate the effects of GPR30 on vascular responsiveness in diabetic ovariectomized (OVX rats and elucidate the possible mechanism involved. The roles of GPR30 were evaluated in the thoracic aorta and cultured endothelial cells. The GPR30 agonist G1 induced a dose-dependent vasodilation in the thoracic aorta of the diabetic OVX rats, which was partially attenuated by the nitric oxide synthase (NOS inhibitor, nitro-L-arginine methylester (L-NAME and the GPR30-selective antagonist G15. Dose-dependent vasoconstrictive responses to phenylephrine were attenuated significantly in the rings of the thoracic aorta following the acute G1 administration in the diabetic OVX rats. This effect of G1 was abolished partially by L-NAME and G15. The acute administration of G1 increased significantly the eNOS activity and the concentration of NO in the endothelial cells exposed to high glucose. G1 treatment induced an enhanced endothelium-dependent relaxation to acetylcholine (Ach in the diabetic OVX rats. Further examination revealed that G1 induced vasodilation in the diabetic OVX rats by increasing the phosphorylation of eNOS. These findings provide preliminary evidence that GPR30 activation leads to eNOS activation, as well as vasodilation, to a certain degree and has beneficial effects on vascular function in diabetic OVX rats.

  19. Characterisation of the vascular pathology in Sigmodon hispidus (Rodentia: Cricetidae following experimental infection with Angiostrongylus costaricensis (Nematoda: Metastrongylidae

    Directory of Open Access Journals (Sweden)

    Danielle Ingrid Bezerra de Vasconcelos

    Full Text Available BACKGROUND Angiostrongylus costaricensis is a nematode that causes human abdominal angiostrongyliasis, a disease found mainly in Latin American countries and particularly in Brazil and Costa Rica. Its life cycle involves exploitation of both invertebrate and vertebrate hosts. Its natural reservoir is a vertebrate host, the cotton rat Sigmodon hispidus. The adult worms live in the ileo-colic branches of the upper mesenteric artery of S. hispidus, causing periarteritis. However, there is a lack of data on the development of vasculitis in the course of infection. OBJECTIVE To describe the histopathology of vascular lesions in S. hispidus following infection with A. costaricensis. METHODS Twenty-one S. hispidus were euthanised at 30, 50, 90 and 114 days post-infection (dpi, and guts and mesentery (including the cecal artery were collected. Tissues were fixed in Carson’s Millonig formalin, histologically processed for paraffin embedding, sectioned with a rotary microtome, and stained with hematoxylin-eosin, resorcin-fuchsin, Perls, Sirius Red (pH = 10.2, Congo Red, and Azan trichrome for brightfield microscopy analysis. FINDINGS At 30 and 50 dpi, live eggs and larvae were present inside the vasa vasorum of the cecal artery, leading to eosinophil infiltrates throughout the vessel adventitia and promoting centripetal vasculitis with disruption of the elastic layers. Disease severity increased at 90 and 114 dpi, when many worms had died and the intensity of the vascular lesions was greatest, with intimal alterations, thrombus formation, iron accumulation, and atherosclerosis. CONCLUSION In addition to abdominal angiostrongyliasis, our data suggest that this model could be very useful for autoimune vasculitis and atherosclerosis studies.

  20. Infantile myofibroma or lymphatic malformation: differential diagnosis of neonatal cystic cervicofacial lesions.

    Science.gov (United States)

    Merrell, Stephen C; Rahbar, Reza; Alomari, Ahmad I; Padua, Horacio M; Vargas, Sara O; Neufeld, Ellis J; Dearden, Jennifer L; Mulliken, John B; Greene, Arin K

    2010-03-01

    A 5-day-old male neonate was referred to our vascular anomalies center with a large cystic submandibular mass. History and physical examination and ultrasonographic results indicated the diagnosis to be macrocystic lymphatic malformation. Consequently, the child was treated with sclerotherapy and subtotal excision. The histopathological examination result showed that the lesion was infantile myofibroma. This diagnostic error was attributed to atypical features of infantile myofibroma in this child: unusually large cysts, rapid enlargement, and coagulopathy. This report expands the clinical spectrum of infantile myofibromatosis and suggests its consideration in the differential diagnosis of neonatal cystic cervicofacial lesions.

  1. Development of a unique mouse model for pancreatic cancer lymphatic metastasis.

    Science.gov (United States)

    Long, Jiang; Luo, Guopei; Liu, Chen; Cui, Xiaobo; Satoh, Kei; Xiao, Zhiwen; Zhang, Bo; Xu, Jin; Ni, Quanxing; Li, Min; Yu, Xianjun

    2012-11-01

    Lymphatic metastasis of pancreatic cancer is a predictor of poor prognosis. However, the molecular mechanisms are largely unknown, thus, making the development of appropriate cell lines and experimental models critically important for future investigations. The purpose of the present study was to establish a 'pancreatic cancer cell and mouse model with high lymphatic metastasis potential' for in-depth study of the underlying mechanisms. The BxPC-3-LN subline, derived from the BxPC-3 human pancreatic cancer cell line, was established through serial passages in nude mice via footpad injections. The subline was able to develop notable lymphatic metastases in 100% of the recipient mice 8 weeks after tumor cell implantation. Compared with the parental BxPC-3 cells, BxPC-3-LN cells were more aggressive, displaying invasive ultrastructure, increased migration and invasion ability, and chemoresistance. Metastasis-related gene alteration including upregulation of MMP14, MMP24, MIF and ADRM1, and downregulation of TGFB2 and ROBO1 were also observed in BxPC-3-LN cells by cDNA microarrays. Thus, the newly selected BxPC-3-LN subline can serve as a unique model for further study of lymphatic metastasis of pancreatic cancer.

  2. Effect of pioglitazone, quercetin, and hydroxy citric acid on vascular endothelial growth factor messenger RNA (VEGF mRNA) expression in experimentally induced nonalcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Surapaneni, Krishna Mohan; Vishnu Priya, Veeraraghavan; Mallika, Jainu

    2015-01-01

    Vascular endothelial growth factor (VEGF) is associated with various ischemic and inflammatory diseases, and plays an important role in the development of liver fibrosis and hepatocarcinogenesis in nonalcoholic steatohepatitis (NASH). In this study, the comparative effect of pioglitazone, quercetin, and hydroxy citric acid on VEGF mRNA in experimentally induced NASH was investigated. The experimental protocol consisted of five groups: control, NASH, NASH + pioglitazone, NASH + quercetin, and NASH + hydroxy citric acid. The VEGF mRNA expression was evaluated by reverse transcription polymerase chain reaction (RT- PCR) analysis for all experimental groups, and the levels of VEGF mRNA were quantitatively measured by densitometry. A higher expression of VEGF mRNA was found in the hepatic cells of rats with experimentally induced NASH compared to the control group. A very mild increase in VEGF mRNA expression was observed in the rats treated with quercetin. In contrast, a mild increase in the expression of VEGF mRNA was observed in the rats treated with pioglitazone and hydroxy citric acid. Quercetin exhibited an effective inhibition of VEGF mRNA expression, while a lower inhibition of the VEGF mRNA level was observed in the hydroxy citric acid- and the pioglitazone-treated rats.

  3. Lymphatic endothelium forms integrin-engaging 3D structures during DC transit across inflamed lymphatic vessels.

    Science.gov (United States)

    Teijeira, Alvaro; Garasa, Saray; Peláez, Rafael; Azpilikueta, Arantza; Ochoa, Carmen; Marré, Diego; Rodrigues, Magda; Alfaro, Carlos; Aubá, Cristina; Valitutti, Salvatore; Melero, Ignacio; Rouzaut, Ana

    2013-09-01

    Dendritic cell (DC) transmigration across the lymphatic endothelium is critical for the initiation and sustenance of immune responses. Under noninflammatory conditions, DC transit across the lymphatic endothelial cell (LEC) has been shown to be integrin independent. In contrast, there is increasing evidence for the participation of integrins and their ligands in DC transit across lymphatic endothelium under inflammation. In this sense, we describe the formation of ICAM-1 (CD54)-enriched three-dimensional structures on LEC/DC contacts, as these DCs adhere to inflamed skin lymphatic vessels and transmigrate into them. In vitro imaging revealed that under inflammation ICAM-1 accumulated on microvilli projections surrounding 60% of adhered DCs. In contrast, these structures were scarcely formed in noninflammatory conditions. Furthermore, ICAM-1-enriched microvilli were important in promoting DC transendothelial migration and DC crawling over the LEC surface. Microvilli formation was dependent on the presence of β-integrins on the DC side and on integrin conformational affinity to ligand. Finally, we observed that LEC microvilli structures appeared in close vicinity of CCL21 depots and that their assembly was partially inhibited by CCL21-neutralizing antibodies. Therefore, under inflammatory conditions, integrin ligands form three-dimensional membrane projections around DCs. These structures offer docking sites for DC transit from the tissue toward the lymphatic vessel lumen.

  4. Thoraco-abdominal high-pitch dual-source CT angiography: Experimental evaluation of injection protocols with an anatomical human vascular phantom

    Energy Technology Data Exchange (ETDEWEB)

    Puippe, Gilbert D., E-mail: gilbert.puippe@usz.ch [Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Switzerland Raemistrasse 100, CH-8091 Zurich (Switzerland); Winklehner, Anna [Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Switzerland Raemistrasse 100, CH-8091 Zurich (Switzerland); Hasenclever, Peter; Plass, André [Division of Cardiac and Vascular Surgery, University Hospital Zurich, Switzerland Raemistrasse 100, CH-8091 Zurich (Switzerland); Frauenfelder, Thomas; Baumueller, Stephan [Institute for Diagnostic and Interventional Radiology, University Hospital Zurich, Switzerland Raemistrasse 100, CH-8091 Zurich (Switzerland)

    2012-10-15

    Objective: To experimentally evaluate three different contrast injection protocols at thoraco-abdominal high-pitch dual-source computed tomography angiography (CTA), with regard to level and homogeneity of vascular enhancement at different cardiac outputs. Materials and methods: A uniphasic, a biphasic as well as an individually tailored contrast protocol were tested using a human vascular phantom. Each protocol was scanned at 5 different cardiac outputs (3–5 L/min, steps of 0.5 L/min) using an extracorporeal cardiac pump. Vascular enhancement of the thoraco-abdominal aorta was measured every 5 cm. Overall mean enhancement of each protocol and mean enhancement for each cardiac output within each protocol were calculated. Enhancement homogeneity along the z-axis was evaluated for each cardiac output and protocol. Results: Overall mean enhancement was significantly higher in the uniphasic than in the other two protocols (all p < .05), whereas the difference between the biphasic and tailored protocol was not significant (p = .76). Mean enhancement among each of the 5 cardiac outputs within each protocol was significantly different (all p < .05). Only within the tailored protocol mean enhancement differed not significantly at cardiac outputs of 3.5 L/min vs. 5 L/min (484 ± 25 HU vs. 476 ± 19 HU, p = .14) and 4 vs. 5 L/min (443 ± 49 HU vs. 476 ± 19 HU, p = .05). Both, uniphasic and tailored protocol yielded homogenous enhancement at all cardiac outputs, whereas the biphasic protocol failed to achieve homogenous enhancement. Conclusion: This phantom study suggests that diagnostic and homogenous enhancement at thoraco-abdominal high-pitch dual-source CTA is feasible with either a uniphasic or an individually tailored contrast protocol.

  5. Lymphatic opacification in the prosthetic hip

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, R.A.; Gheorghiu, D. (Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Radiology); Krausz, Y. (Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Nuclear Medicine)

    1991-01-01

    A retrospective analysis of 52 patients with hip pain following total hip replacement was made. Each of them was evaluated by plain radiographs, technetium 99m pyrophosphate scans, arthrography with plain film substraction technique, and culture of joint fluid. In 30 cases there was evidence of prosthetic loosening, and in 21 of these lymphangeal opacification during arthrography was seen. In 15 cases with lymphongeal opacification the daignosis of prosthetic loosening was subsequently confirmed by prosthetic revision. In none of the 22 cases in which no evidence of prosthetic loosening was seen was there lymphatic opacification. It is concluded that lymphatic opacification during arthrography for pain following total hip prosthesis is a valuable ancillary sign of loosening. (orig.).

  6. Lymphatic injury at sacrocolpopexy: an unusual complication.

    Science.gov (United States)

    Suen, Michael W H; Geoffrion, Roxana

    2014-04-01

    Lymphorrhea is a rare condition with a paucity of reports in the gynaecologic literature. The most frequent causes are invasive procedures and surgical interventions. A multiparous woman underwent a total abdominal hysterectomy with prophylactic bilateral salpingectomy and abdominal sacrocolpopexy for pelvic organ prolapse. During retroperitoneal dissection, clear fluid discharge was encountered. Ureteric injury was subsequently ruled out. A sample of the fluid was taken to confirm lymphatic injury. Ligation suture and closing the peritoneum slowed fluid drainage. To our knowledge, this is the first reported lymphatic injury in association with a urogynaecologic procedure. Gynaecologists should be aware of this potential complication and should have an approach to diagnosis and management. This case highlights the importance of intraoperative consultation.

  7. Spontaneous activity in peripheral diaphragmatic lymphatic loops.

    Science.gov (United States)

    Moriondo, Andrea; Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela

    2013-10-01

    The spontaneous contractility of FITC-dextran-filled lymphatics at the periphery of the pleural diaphragm was documented for the first time "in vivo" in anesthetized Wistar rats. We found that lymphatic segments could be divided into four phenotypes: 1) active, displaying rhythmic spontaneous contractions (51.8% of 197 analyzed sites); 2) stretch-activated, whose contraction was triggered by passive distension of the vessel lumen (4.1%); 3) passive, which displayed a completely passive distension (4.5%); and 4) inert, whose diameter never changed over time (39.6%). Smooth muscle actin was detected by immunofluorescence and confocal microscopy in the vessel walls of active but also of inert sites, albeit with a very different structure within the vessel wall. Indeed, while in active segments, actin was arranged in a dense mesh completely surrounding the lumen, in inert segments actin decorated the vessels wall in sparse longitudinal strips. When located nearby along the same lymphatic loop, active, stretch-activated, and passive sites were always recruited in temporal sequence starting from the active contraction. The time delay was ∼0.35 s between active and stretch-activated and 0.54 s between stretch-activated and passive segments, promoting a uniform lymph flux of ∼150/200 pl/min. We conclude that, unlike more central diaphragmatic lymphatic vessels, loops located at the extreme diaphragmatic periphery do require an intrinsic pumping mechanism to propel lymph centripetally, and that such an active lymph propulsion is attained by means of a complex interplay among sites whose properties differ but are indeed able to organize lymph flux in an ordered fashion.

  8. Lymphatic vessels arise from specialized angioblasts within a venous niche.

    Science.gov (United States)

    Nicenboim, J; Malkinson, G; Lupo, T; Asaf, L; Sela, Y; Mayseless, O; Gibbs-Bar, L; Senderovich, N; Hashimshony, T; Shin, M; Jerafi-Vider, A; Avraham-Davidi, I; Krupalnik, V; Hofi, R; Almog, G; Astin, J W; Golani, O; Ben-Dor, S; Crosier, P S; Herzog, W; Lawson, N D; Hanna, J H; Yanai, I; Yaniv, K

    2015-06-04

    How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the ‘angioblast-to-lymphatic’ transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

  9. Non-endemic cases of lymphatic filariasis.

    Science.gov (United States)

    Jones, Robert T

    2014-11-01

    Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history. © 2014 John Wiley & Sons Ltd.

  10. 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.

  11. A Case of Abnormal Lymphatic-Like Differentiation and Endothelial Progenitor Cell Activation in Neovascularization Associated with Hemi-Retinal Vein Occlusion

    Directory of Open Access Journals (Sweden)

    Sirpa Loukovaara

    2015-07-01

    Full Text Available Purpose: Pathological vascular differentiation in retinal vein occlusion (RVO-related neovessel formation remains poorly characterized. The role of intraocular lymphatic-like differentiation or endothelial progenitor cell activity has not been studied in this disease. Methods: Vitrectomy was performed in an eye with hemi-RVO; the neovessel membrane located at the optic nerve head was removed and subjected to immunohistochemistry. Characterization of the neovascular tissue was performed using hematoxylin and eosin, α-smooth muscle actin, and the pan-endothelial cell (EC adhesion molecule CD31. The expression of lymphatic EC markers was studied by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1, podoplanin (PDPN, and prospero-related homeobox protein 1 (Prox-1. Potential vascular stem/progenitor cells were identified by active cellular proliferation (Ki67 and expression of the stem cell marker CD117. Results: The specimen contained blood vessels lined by ECs and surrounded by pericytes. Immunoreactivity for LYVE-1 and Prox-1 was detected, with Prox-1 being more widely expressed in the active Ki67-positive lumen-lining cells. PDPN expression was instead found in the cells residing in the extravascular tissue. Expression of the stem cell markers CD117 and Ki67 suggested vascular endothelial progenitor cell activity. Conclusions: Intraocular lymphatic-like differentiation coupled with progenitor cell activation may be involved in the pathology of neovessel formation in ischemia-induced human hemi-RVO.

  12. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-11-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  13. Insights into the Pathogenesis of Disease in Human Lymphatic Filariasis

    OpenAIRE

    Thomas B Nutman

    2013-01-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce lymphatic dilatation. Progressive lymphatic damage and pathology results primarily from...

  14. Corneal Lymphatic Valve Formation in Relation to Lymphangiogenesis

    Science.gov (United States)

    Truong, Tan; Huang, Eric; Yuen, Don; Chen, Lu

    2014-01-01

    Purpose. We have recently provided evidence showing that luminal lymphatic valves are formed right after the onset of corneal inflammatory lymphangiogenesis (LG). The purpose of this study was to further characterize the long-term time course, spatial distribution, directional orientation, and functional implications of the valve formation in relation to corneal LG. Methods. Corneal LG was induced in normal adult BALB/c mice by a modified suture placement model with equal distribution in the nasal and temporal side. Whole-mount corneas were harvested every 2 weeks for up to 8 weeks post suturing for immunofluorescent microscopic assays. Quantitative analysis on both lymphatic vessels and valves was performed by using National Institutes of Health ImageJ software. Corneal lymphatic live imaging was performed to show functional drainage of the valves. Results. Lymphatic vessel invasion areas at 4, 6, and 8 weeks were significantly less than the peak at 2 weeks post corneal suturing. In contrast, the ratio of lymphatic valves to vessel invasion area was at its lowest at 2 weeks with a peak approximately at 6 weeks post suturing. Lymphatic valves were more localized in the nasal quadrant at all time points studied, and most of the well-formed valves were directionally oriented toward the limbus. The lymphatic valves function to guide lymphatic drainage outside the cornea. Conclusions. This study presents new insights into corneal lymphatic valve formation and function in inflammatory LG. Further investigation on lymphatic valves may provide novel strategies to interfere with lymphatic maturation and function and to treat lymphatic-related disorders. PMID:24595382

  15. Functional lymphatic imaging in tumor-bearing mice

    OpenAIRE

    Kwon, Sunkuk; Eva M. Sevick-Muraca

    2010-01-01

    The lymphatic system provides a route for dissemination of metastatic cancer cells. Yet to date transient changes in lymphatic drainage pathways and function as a result of tumor growth and metastasis has not been completely elucidated. Herein, we non-invasively imaged functional and architectural lymphatic changes in mice with regional, palpable lymph node (LN) involvement using dynamic near-infrared (NIR) fluorescence imaging with intradermal injection of indocyanine green (ICG) to both tum...

  16. Corneal lymphatic valve formation in relation to lymphangiogenesis.

    Science.gov (United States)

    Truong, Tan; Huang, Eric; Yuen, Don; Chen, Lu

    2014-03-25

    We have recently provided evidence showing that luminal lymphatic valves are formed right after the onset of corneal inflammatory lymphangiogenesis (LG). The purpose of this study was to further characterize the long-term time course, spatial distribution, directional orientation, and functional implications of the valve formation in relation to corneal LG. Corneal LG was induced in normal adult BALB/c mice by a modified suture placement model with equal distribution in the nasal and temporal side. Whole-mount corneas were harvested every 2 weeks for up to 8 weeks post suturing for immunofluorescent microscopic assays. Quantitative analysis on both lymphatic vessels and valves was performed by using National Institutes of Health ImageJ software. Corneal lymphatic live imaging was performed to show functional drainage of the valves. Lymphatic vessel invasion areas at 4, 6, and 8 weeks were significantly less than the peak at 2 weeks post corneal suturing. In contrast, the ratio of lymphatic valves to vessel invasion area was at its lowest at 2 weeks with a peak approximately at 6 weeks post suturing. Lymphatic valves were more localized in the nasal quadrant at all time points studied, and most of the well-formed valves were directionally oriented toward the limbus. The lymphatic valves function to guide lymphatic drainage outside the cornea. This study presents new insights into corneal lymphatic valve formation and function in inflammatory LG. Further investigation on lymphatic valves may provide novel strategies to interfere with lymphatic maturation and function and to treat lymphatic-related disorders.

  17. Lymphatic malformations: A dilemma in diagnosis and management

    Directory of Open Access Journals (Sweden)

    Ramashankar

    2014-01-01

    Full Text Available Lymphatic malformations of the head and neck, also known as lymphangiomas or cystic hygromas, are a diverse group of lesions. Lymphangiomas represent benign hamartomatous tumors of lymphatic vessels with a marked predilection for the head, neck and oral cavity. These lesions, like most of the swellings occurring in the neck, frequently pose a dilemma in diagnosis and treatment. This is a case report of a lymphatic malformation which presented as a painless mass in the lower border of mandible.

  18. A case of lymphatic malformation/lymphangioma of the scrotum

    OpenAIRE

    Gensuke Akaike; Taiki Nozaki; Akari Makidono; Yukihisa Saida; Takeshi Hirabayashi; Koyu Suzuki

    2012-01-01

    Lymphatic malformation/lymphangioma of the scrotum is rare. It is caused by lymphatic abnormalities and the most common sites are the neck and axilla. The scrotum is one of the most uncommon sites. We report the case of a 12-year-old boy with pathologically confirmed cystic lymphangioma/lymphatic malformation in the scrotum. The diagnosis was suspected from ultrasonography and magnetic resonance imaging. The most common cause of a cystic mass in the scrotum is scrotal hydrocele, but cystic ly...

  19. Involvement of neurons and retinoic acid in lymphatic development: new insights in increased nuchal translucency

    NARCIS (Netherlands)

    Burger, N.B.; Stuurman, K.E.; Kok, E.; Konijn, T.; Schooneman, D.; Niederreither, K.; Coles, M.; Agace, W.W.; Christoffels, V.M.; Mebius, R.E.; Pavert, S.A. van de; Bekker, M.N.

    2014-01-01

    OBJECTIVE: Increased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the

  20. Insights into the pathogenesis of disease in human lymphatic filariasis.

    Science.gov (United States)

    Nutman, Thomas B

    2013-09-01

    Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce lymphatic dilatation. Progressive lymphatic damage and pathology results primarily from the host inflammatory response to the parasites but also perhaps from the host inflammatory response to the parasite's Wolbachia endosymbiont and as a consequence of superimposed bacterial or fungal infections. This review will attempt to shed light on disease pathogenesis in lymphatic filariasis.

  1. A model for fluid drainage by the lymphatic system.

    Science.gov (United States)

    Heppell, Charles; Richardson, Giles; Roose, Tiina

    2013-01-01

    This study investigates the fluid flow through tissues where lymphatic drainage occurs. Lymphatic drainage requires the use of two valve systems, primary and secondary. Primary valves are located in the initial lymphatics. Overlapping endothelial cells around the circumferential lining of lymphatic capillaries are presumed to act as a unidirectional valve system. Secondary valves are located in the lumen of the collecting lymphatics and act as another unidirectional valve system; these are well studied in contrast to primary valves. We propose a model for the drainage of fluid by the lymphatic system that includes the primary valve system. The analysis in this work incorporates the mechanics of the primary lymphatic valves as well as the fluid flow through the interstitium and that through the walls of the blood capillaries. The model predicts a piecewise linear relation between the drainage flux and the pressure difference between the blood and lymphatic capillaries. The model describes a permeable membrane around a blood capillary, an elastic primary lymphatic valve and the interstitium lying between the two.

  2. A case of lymphatic malformation/lymphangioma of the scrotum

    Directory of Open Access Journals (Sweden)

    Gensuke Akaike

    2012-04-01

    Full Text Available Lymphatic malformation/lymphangioma of the scrotum is rare. It is caused by lymphatic abnormalities and the most common sites are the neck and axilla. The scrotum is one of the most uncommon sites. We report the case of a 12-year-old boy with pathologically confirmed cystic lymphangioma/lymphatic malformation in the scrotum. The diagnosis was suspected from ultrasonography and magnetic resonance imaging. The most common cause of a cystic mass in the scrotum is scrotal hydrocele, but cystic lymphangioma/lymphatic malformation should be considered as a differential diagnosis for multicystic scrotal mass.

  3. A case of lymphatic malformation/lymphangioma of the scrotum.

    Science.gov (United States)

    Akaike, Gensuke; Nozaki, Taiki; Makidono, Akari; Saida, Yukihisa; Hirabayashi, Takeshi; Suzuki, Koyu

    2012-01-01

    Lymphatic malformation/lymphangioma of the scrotum is rare. It is caused by lymphatic abnormalities and the most common sites are the neck and axilla. The scrotum is one of the most uncommon sites. We report the case of a 12-year-old boy with pathologically confirmed cystic lymphangioma/lymphatic malformation in the scrotum. The diagnosis was suspected from ultrasonography and magnetic resonance imaging. The most common cause of a cystic mass in the scrotum is scrotal hydrocele, but cystic lymphangioma/lymphatic malformation should be considered as a differential diagnosis for multicystic scrotal mass.

  4. Dual-energy CT based vascular iodine analysis improves sensitivity for peripheral pulmonary artery thrombus detection: An experimental study in canines

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun Xiang [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Zhang, Long Jiang, E-mail: kevinzhlj@163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Han, Zong Hong; Zhou, Chang Sheng [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Krazinski, Aleksander W.; Silverman, Justin R. [Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China); Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Lu, Guang Ming, E-mail: cjr.luguangming@vip.163.com [Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu 210002 (China)

    2013-12-01

    Purpose: To evaluate the performance of dual-energy CT (DECT) based vascular iodine analysis for the detection of acute peripheral pulmonary thrombus (PE) in a canine model with histopathological findings as the reference standard. Materials and methods: The study protocol was approved by our institutional animal committee. Thrombi (n = 12) or saline (n = 4) were intravenously injected via right femoral vein in sixteen dogs, respectively. CT pulmonary angiography (CTPA) in DECT mode was performed and conventional CTPA images and DECT based vascular iodine studies using Lung Vessels application were reconstructed. Two radiologists visually evaluated the number and location of PEs using conventional CTPA and DECT series on a per-animal and a per-clot basis. Detailed histopathological examination of lung specimens and catheter angiography served as reference standard. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of DECT and CTPA were calculated on a segmental and subsegmental or more distal pulmonary artery basis. Weighted κ values were computed to evaluate inter-modality and inter-reader agreement. Results: Thirteen dogs were enrolled for final image analysis (experimental group = 9, control group = 4). Histopathological results revealed 237 emboli in 45 lung lobes in 9 experimental dogs, 11 emboli in segmental pulmonary arteries, 49 in subsegmental pulmonary arteries, 177 in fifth-order or more distal pulmonary arteries. Overall sensitivity, specificity, accuracy, PPV, and NPV for CTPA plus DECT were 93.1%, 76.9%, 87.8%, 89.4%, and 84.2% for the detection of pulmonary emboli. With CTPA versus DECT, sensitivities, specificities, accuracies, PPVs, and NPVs are all 100% for the detection of pulmonary emboli on a segmental pulmonary artery basis, 88.9%, 100%, 96.0%, 100%, and 94.1% for CTPA and 90.4%, 93.0%, 92.0%, 88.7%, and 94.1% for DECT on a subsegmental pulmonary artery basis; 23.8%, 96.4%, 50.4%, 93

  5. Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart Disease.

    Science.gov (United States)

    Dori, Yoav; Keller, Marc S; Rome, Jonathan J; Gillespie, Matthew J; Glatz, Andrew C; Dodds, Kathryn; Goldberg, David J; Goldfarb, Samuel; Rychik, Jack; Itkin, Maxim

    2016-03-22

    Plastic bronchitis is a potentially fatal disorder occurring in children with single-ventricle physiology, and other diseases, as well, such as asthma. In this study, we report findings of abnormal pulmonary lymphatic flow, demonstrated by MRI lymphatic imaging, in patients with plastic bronchitis and percutaneous lymphatic intervention as a treatment for these patients. This is a retrospective case series of 18 patients with surgically corrected congenital heart disease and plastic bronchitis who presented for lymphatic imaging and intervention. Lymphatic imaging included heavy T2-weighted MRI and dynamic contrast-enhanced magnetic resonance lymphangiogram. All patients underwent bilateral intranodal lymphangiogram, and most patients underwent percutaneous lymphatic intervention. In 16 of 18 patients, MRI or lymphangiogram or both demonstrated retrograde lymphatic flow from the thoracic duct toward lung parenchyma. Intranodal lymphangiogram and thoracic duct catheterization was successful in all patients. Seventeen of 18 patients underwent either lymphatic embolization procedures or thoracic duct stenting with covered stents to exclude retrograde flow into the lungs. One of the 2 patients who did not have retrograde lymphatic flow did not undergo a lymphatic interventional procedure. A total of 15 of 17(88%) patients who underwent an intervention had significant symptomatic improvement at a median follow-up of 315 days (range, 45-770 days). The most common complication observed was nonspecific transient abdominal pain and transient hypotension. In this study, we demonstrated abnormal pulmonary lymphatic perfusion in most patients with plastic bronchitis. Interruption of the lymphatic flow resulted in significant improvement of symptoms in these patients and, in some cases, at least temporary resolution of cast formation. © 2016 American Heart Association, Inc.

  6. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers.

    Science.gov (United States)

    Belgrado, Jean-Paul; Vandermeeren, Liesbeth; Vankerckhove, Sophie; Valsamis, Jean-Baptiste; Malloizel-Delaunay, Julie; Moraine, Jean-Jacques; Liebens, Fabienne

    2016-06-01

    There are very little scientific data on occlusion pressure for superficial lymphatic collectors. Given its importance in determining the transport capacity of lymphatic vessels, it is crucial to know its value. The novel method of near-infrared fluorescence lymphatic imaging (NIRFLI) can be used to visualize lymphatic flow in real time. The goal of this study was to see if this method could be used to measure the lymphatic occlusion pressure. We observed and recorded lymph flow in the upper limb of healthy volunteers through a transparent cuff using near-infrared fluorescence lymphatic imaging. After obtaining a baseline of the lymph flow without pressure inside the cuff, the cuff was inflated by increments of 10 mm Hg starting at 30 mm Hg. A NIRFLI guided manual lymphatic drainage technique named "Fill & Flush Drainage Method" was performed during the measurement to promote lymph flow. Lymphatic occlusion pressure was determined by observing when lymph flow stopped under the cuff. We measured the lymphatic occlusion pressure on 30 healthy volunteers (11 men and 19 women). Mean lymphatic occlusion pressure in the upper limb was 86 mm Hg (CI ±3.7 mm Hg, α = 0.5%). No significant differences were found between age groups (p = 0.18), gender (p = 0.12), or limb side (p = 0.85). NIRFLI, a transparent sphygmomanometer cuff and the "Fill and Flush" manual lymphatic drainage method were used to measure the lymphatic occlusion pressure in 30 healthy humans. That combination of these techniques allows the visualization of the lymph flow in real time, while ensuring the continuous filling of the lymph collectors during the measurement session, reducing false negative observations. The measured occlusion pressures are much higher than previously described in the medical literature.

  7. [Experimental study on effect of allicin in inhibiting insulin-induced vascular smooth muscle cell proliferation and migration].

    Science.gov (United States)

    Li, Ting; Xia, Yong

    2014-10-01

    To investigate the effect of allicin in inhibiting insulin-induced vascular smooth muscle cell (VSMC) proliferation and migration. The tissue explant method was adopted to culture rat's aVSMCs, and the immunofluorescence method was used to identify α-SMA. Cells from the third to fifth generations were selected in the experiment The insulin-induced VSMC model was established. The experiment was carried out in five groups: the control group, the insulin group, the allicin group, the ERK inhibitors PD98059 group (20 μmol · L(-1)) and the PD98059 + allicin group. VSMCs' proliferation was determined by CCK8 colorimetric method, while its migration was detected by cell counting; The western blotting was used to detect total ERK, Phospho-ERK, PCNA protein's expression. Primary cultured VSMCs grew well in the spindle shape under the lightmicroscope, with peak and valley. α-SMA immunofluorescence results showed that the cultured cells had typical VSMCs' features. Insulin could stimulate VSMCs' proliferation and migration, with the best effect at the concentration of 100 nmol · L(-1). The pretreatment with allicin could significantly inhibit VSMCs' proliferation and migration induced by insulin in a dose-dependent manner. The pretreatment with PD98059 and allicin + PD98059 could inhibit VSMCs' proliferation and migration induced by insulin remarkably as well. Insulin could significantly accelerate VSMCs' expression of such proteins as p-ERK, PCNA. Contrarily, allicin could notably inhibit VSMCs' expression of such proteins as p-ERK, PCNA in a dose-dependent manner. Allicin could significantly inhibit VSMCs' proliferation and migration induced by insulin, which may be related to the inhibition of the activation of ERK signal path.

  8. Cervicofacial Lymphatic Malformations: A Retrospective Review of 40 Cases

    Directory of Open Access Journals (Sweden)

    Byung Chae Cho

    2016-01-01

    Full Text Available BackgroundLymphatic malformation (LM is a form of congenital vascular malformation with a low incidence. Although LM has been studied, no consensus has emerged regarding its cause or treatment.MethodsIn this study, we retrospectively evaluated 40 patients who visited our vascular anomalies center for the treatment of cervicofacial LM, which is a common manifestation of LM. The medical records of patients over a period of 12 years were reviewed and analyzed for commonalities regarding the diagnosis and the results of treatment.ResultsSuspected cervicofacial LM was confirmed through imaging studies. No difference in incidence was observed according to sex, and 73% of patients first presented with symptoms before the age of two years. The left side and the V2–V3 area were most commonly affected. No significant differences in incidence were observed among the macrocystic, microcystic, and combined types of LM. A total of 28 out of 36 patients received sclerotherapy as the first choice of treatment, regardless of the type of lesion. Complete resolution was achieved in only 25% of patients.ConclusionsLM is important to confirm the diagnosis early and to choose an appropriate treatment strategy according to the stage of the disease and each individual patient's symptoms. When treatment is delayed or an incorrect treatment is administered, patient discomfort increases as the lesion gradually spreads. Therefore, more so than is the case for most other diseases, a team approach on a case-by-case basis is important for the accurate and appropriate treatment of LM.

  9. 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

    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...... 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....

  10. Vascular Cures

    Science.gov (United States)

    ... is the first national program to bring the power of the patient to vascular research and care. ... Our recent national Vascular Research Summit brought together leaders from 31 institutions to generate collaborative projects for ...

  11. Adipose Tissue-Derived Stromal Vascular Fraction Increases Osteogenesis in an Experimental Design Zygomatic Bone Defect Model.

    Science.gov (United States)

    Toplu, Gaye; Ozcelik, Derya; Serin, Merdan; Erdem, Havva; Topacoglu, Arzu Turkseven

    2017-11-01

    Facial bone defects are frequently encountered problems in clinical practice. Bone grafts, flaps, and alloplastic materials are often used in their treatment. This leads to donor site morbidity and prolongation of the operation. The authors have planned this study to examine whether adipose tissue derived stromal vascular fraction (SVF) has an osteogenic effect in the critical sized membranous bone defect of the zygomatic bone. Twenty male Wistar Albino rats were used. Bilateral zygomatic arches were opened with lateral incisions. A standard 3-mm bone defect was created bilaterally on the zygomatic arches of the rats. In the experiment side, the stem cell-rich SVF that was obtained by applying centrifugal process to the adipose tissue derived from the inguinal fat pad was injected into the site of the right zygomatic arch bone defect. In the control side, left zygomatic arch was left for secondary bone healing without any treatment after a 3-mm critical bone defect was created. In the postoperative 10th (n:5) and 20th weeks (n:13), the healing areas of bone defects were assessed by a 3-dimensional tomography, and then, the rats were sacrificed and bone healing was examined histologically. There were no statistically significant differences on the 10th week results. At the 20th week new bone formation amount calculated from the 3-dimensional computed tomography results was significantly higher in the experiment side (P = 0.033). In the histological examination at the 20th week, there was significantly more callus formation in the experiment side (P = 0.0112). Stem cells can increase the rate of bone healing by differentiating into certain tissues. It is predicted that adipose tissue-derived SVF rich with mesenchymal stem cells can increase bone healing in facial bone defects and this application could replace the use of bone grafts and flaps in clinical practice. As a result, it is concluded that adipose tissue-derived stem cells can potentiate osteogenesis

  12. 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.

  13. BMP-SMAD signalling output is highly regionalized in cardiovascular and lymphatic endothelial networks.

    Science.gov (United States)

    Beets, Karen; Staring, Michael W; Criem, Nathan; Maas, Elke; Schellinx, Niels; de Sousa Lopes, Susana M Chuva; Umans, Lieve; Zwijsen, An

    2016-10-10

    Bone morphogenetic protein (BMP) signalling has emerged as a fundamental pathway in endothelial cell biology and deregulation of this pathway is implicated in several vascular disorders. BMP signalling output in endothelial cells is highly context- and dose-dependent. Phosphorylation of the BMP intracellular effectors, SMAD1/5/9, is routinely used to monitor BMP signalling activity. To better understand the in vivo context-dependency of BMP-SMAD signalling, we investigated differences in BMP-SMAD transcriptional activity in different vascular beds during mouse embryonic and postnatal stages. For this, we used the BRE::gfp BMP signalling reporter mouse in which the BMP response element (BRE) from the ID1-promotor, a SMAD1/5/9 target gene, drives the expression of GFP. A mosaic pattern of GFP was present in various angiogenic sprouting plexuses and in endocardium of cardiac cushions and trabeculae in the heart. High calibre veins seemed to be more BRE::gfp transcriptionally active than arteries, and ubiquitous activity was present in embryonic lymphatic vasculature. Postnatal lymphatic vessels showed however only discrete micro-domains of transcriptional activity. Dynamic shifts in transcriptional activity were also observed in the endocardium of the developing heart, with a general decrease in activity over time. Surprisingly, proliferative endothelial cells were almost never GFP-positive. Patches of transcriptional activity seemed to correlate with vasculature undergoing hemodynamic alterations. The BRE::gfp mouse allows to investigate selective context-dependent aspects of BMP-SMAD signalling. Our data reveals the highly dynamic nature of BMP-SMAD mediated transcriptional regulation in time and space throughout the vascular tree, supporting that BMP-SMAD signalling can be a source of phenotypic diversity in some, but not all, healthy endothelium. This knowledge can provide insight in vascular bed or organ-specific diseases and phenotypic heterogeneity within an

  14. Venous Thromboembolism in Pediatric Vascular Anomalies

    Directory of Open Access Journals (Sweden)

    Taizo A. Nakano

    2017-07-01

    Full Text Available The presence of a vascular anomaly suggests that capillaries, veins, arteries, and/or lymphatic vessels have demonstrated abnormal development and growth. Often dilated and misshaped, these vessels augment normal flow of blood and lymphatic fluids that increases the overall risk to develop intralesional thrombosis. Abnormal endothelial and lymphoendothelial cells activate hemostasis and hyperfibrinolytic pathways through poorly understood mechanisms, which contribute to the development of localized intravascular coagulopathy. Vascular malformations, tumors, and complex combined syndromes demonstrate varying degrees of prothrombotic activity and consumptive coagulopathy depending on the vessels involved and the pattern and extent of abnormal growth. The clinical impact of venous thromboembolism in pediatric vascular anomalies varies from painful syndromes that disrupt quality of life to life-threatening embolic disease. There remains little literature on the study, evaluation, and treatment of thrombosis in pediatric vascular anomalies. However, there have been great advances in our ability to image complex lesions, to surgically and interventionally augment disease, and to provide enhanced supportive care including patient education, compression therapy, and strategic use of anticoagulation.

  15. Lymphatic Leak Occurring After Surgical Lymph Node Dissection: A Preliminary Study Assessing the Feasibility and Outcome of Lymphatic Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yoolim; Won, Je Hwan [Ajou University School of Medicine, Department of Radiology, Ajou University Hospital (Korea, Republic of); Kong, Tae-Wook; Paek, Jiheum; Chang, Suk-Joon; Ryu, Hee-Sug [Ajou University School of Medicine, Department of Obstetrics and Gynecology, Gynecologic Cancer Center (Korea, Republic of); Kim, Jinoo, E-mail: jinoomail@gmail.com [Ajou University School of Medicine, Department of Radiology, Ajou University Hospital (Korea, Republic of)

    2016-12-15

    PurposeTo analyze imaging findings of lymphatic leakage associated with surgical lymph node dissection on lymphangiography and assess the outcome of lymphatic embolization.Materials and MethodsThis retrospective study comprised 21 consecutive patients who were referred for lymphatic intervention between March 2014 and April 2015 due to postsurgical lymphatic leaks. Lymphangiography was performed through inguinal lymph nodes to identify the leak. When a leak was found, lymphatic embolization was performed by fine-needle injection of N-butyl cyanoacrylate into the site of leakage or into an inflow lymphatic vessel or into a pelvic lymph node located below the leakage. Electronic medical records and imaging studies were reviewed to assess the outcome.ResultLymphangiography revealed single or multiple leaks in all but one patient. Lymphatic embolization was performed in 20 patients with leaks. Including the patient who did not undergo embolization, 17 patients (81.0 %) showed initial response to treatment. Three patients underwent repeated embolization with successful results. The overall success rate was 95.2 %. The mean duration of hospitalization after lymphatic intervention was 5.9 days. During a mean follow-up period of 11 months, two patients developed localized swelling in the groin following lipiodol injection. There were no complications related to lymphatic embolization. Three patients were found to have developed small, asymptomatic lymphoceles on CT or MRI that did not require further treatment.ConclusionLymphangiography is useful for detecting lymphatic leakage occurring after lymph node dissection. Furthermore, lymphatic embolization is feasible, effective, and safe for managing leaks demonstrated on lymphangiography.

  16. Aged Lymphatic Vessels and Mast Cells in Perilymphatic Tissues.

    Science.gov (United States)

    Pal, Sarit; Meininger, Cynthia J; Gashev, Anatoliy A

    2017-05-03

    This review provides a comprehensive summary of research on aging-associated alterations in lymphatic vessels and mast cells in perilymphatic tissues. Aging alters structure (by increasing the size of zones with low muscle cell investiture), ultrastructure (through loss of the glycocalyx), and proteome composition with a concomitant increase in permeability of aged lymphatic vessels. The contractile function of aged lymphatic vessels is depleted with the abolished role of nitric oxide and an increased role of lymphatic-born histamine in flow-dependent regulation of lymphatic phasic contractions and tone. In addition, aging induces oxidative stress in lymphatic vessels and facilitates the spread of pathogens from these vessels into perilymphatic tissues. Aging causes the basal activation of perilymphatic mast cells, which, in turn, restricts recruitment/activation of immune cells in perilymphatic tissues. This aging-associated basal activation of mast cells limits proper functioning of the mast cell/histamine/NF-κB axis that is essential for the regulation of lymphatic vessel transport and barrier functions as well as for both the interaction and trafficking of immune cells near and within lymphatic collecting vessels. Cumulatively, these changes play important roles in the pathogenesis of alterations in inflammation and immunity associated with aging.

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

    NARCIS (Netherlands)

    van Impel, Andreas; Zhao, Zhonghua; Hermkens, Dorien M A; Roukens, M Guy; Fischer, Johanna C; Peterson-Maduro, Josi; Duckers, Henricus; Ober, Elke A; Ingham, Philip W; Schulte-Merker, Stefan

    In mammals, the homeodomain transcription factor Prox1 acts as the central regulator of lymphatic cell fate. Its restricted expression in a subset of cardinal vein cells leads to a switch towards lymphatic specification and hence represents a prerequisite for the initiation of lymphangiogenesis.

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

    African Journals Online (AJOL)

    Objective: During the wound healing process, lymphatic regeneration in the injured skin has not been fully investigated. This work was designed to study the regeneration of lymphatic vessels in rat incisional wounds in relation to the duration after the wound infliction. Material and methods: We studied the regeneration of ...

  19. Near-Infrared Fluorescence Lymphatic Imaging in Lymphangiomatosis.

    Science.gov (United States)

    Rasmussen, John C; Fife, Caroline E; Sevick-Muraca, Eva M

    2015-09-01

    Lymphangiomatosis is a rare disorder of the lymphatic system that can impact the dermis, soft tissue, bone, and viscera and can be characterized by lymphangiomas, swelling, and chylous discharge. Whether disordered lymphangiogenesis in lymphangiomatosis affects the function and anatomy of the entire systemic lymphatic circulation or is localized to specific sites is not fully known. A 35-year-old Caucasian female diagnosed with whole-body lymphangiomatosis at 2 months of age and who continues to present with progressive disease was imaged with near-infrared fluorescence lymphatic imaging. While the peripheral lymphatics in the extremities appeared largely normal compared to prior studies, we observed tortuous lymphatic vessels, fluorescence drainage from the peripheral lymphatics into lymphangiomas, and extensive dermal lymphatics in the left thigh and inguinal regions where the subject had previously had surgical assaults, potentially indicating defective systemic lymphangiogenesis. Further research into anatomical and functional lymphatic changes associated with the progression and treatment of lymphangiomatosis could aid in understanding the pathophysiology of the disease as well as point to treatment strategies.

  20. Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions.

    Science.gov (United States)

    Windsperger, Karin; Dekan, Sabine; Pils, Sophie; Golletz, Carsten; Kunihs, Victoria; Fiala, Christian; Kristiansen, Glen; Knöfler, Martin; Pollheimer, Jürgen

    2017-06-01

    Do extravillous trophoblasts (EVTs) invade non-arterial decidual vessels in healthy and pathological pregnancies? Our results reveal that trophoblast invasion of venous and lymphatic vessels is a frequent event during the first trimester of pregnancy and is compromised in  recurrent spontaneous abortion (RSA). In addition, the present data suggest that EVTs populate regional lymph nodes during pregnancy. Human trophoblasts remodel and invade decidual spiral arteries. In addition, a recent report demonstrates that trophoblasts contact and invade decidual veins. Tissue samples of human first trimester deciduae basalis (n = 54, 6th-13th weeks of gestation) obtained from elective pregnancy terminations were used to study trophoblast invasion into veins and lymphatics, in comparison to arteries. Age-matched cases of idiopathic, recurrent spontaneous abortions tissue samples (n = 23) were assessed for cell numbers of EVTs in these decidual vessels. In addition, lymph nodes of four pregnant women were analysed for the presence of EVTs. Localization, frequency and EVT-mediated targeting and invasion of arterial, venous as well as lymphatic vessels were determined in first trimester decidua basalis tissue sections using immunofluorescence staining with antibodies against CD31, CD34, ephrin B2 (EFNB2), ephrin receptor B4 (EPHB4), HLA-G, podoplanin, prospero-related homeobox 1 (Prox-1), alpha-smooth muscle actin 2 (ATCTA2), von willebrand factor (vWF) and proteoglycan 2 (PRG2). Arterial, venous and lymphatic-associated EVTs were further characterized according to their position in the vascular structure and classified as intramural (im) or intraluminal (il). EVTs, specifically expressing PRG2, target and invade veins and lymphatics in first trimester decidua basalis since HLA-G+ trophoblast were detected in the vascular wall (intramural EVT, imEVTs) and in the lumen of these vessels (intraluminal EVT, ilEVTs). In total, 276 arteries, 793 veins and 113 lymphatics were

  1. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Imaging the lymphatic system: possibilities and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Clement, Olivier [Service de Radiologie, Hopital Europeen Georges Pompidou, 20 rue Leblanc, 75908, Paris Cedex 15 (France); Luciani, Alain [Service de Radiologie, Hopital Henri Mondor, Creteil (France)

    2004-08-01

    The lymphatic system is anatomically complex and difficult to image. Lymph ducts are responsible for the drainage of part of the body's interstitial fluid. Lymph nodes account for the enrichment of lymph fluid, and can be involved in a large variety of diseases, especially cancer. For a long time, lymphatic imaging was limited to the sole use of conventional lymphography involving invasive procedures and patient discomfort. New contrast agents and techniques in ultrasound, nuclear medicine, and MR imaging are now available for imaging of both the lymphatic vessels and the lymph nodes. The objective of this review is to discuss the different imaging modalities of the lymphatic system, with a special focus on the new possibilities of lymphatic imaging including enhanced MR lymphography, sentinel node and positron emission tomography imaging, and contrast-enhanced ultrasound. (orig.)

  3. How Do Meningeal Lymphatic Vessels Drain the CNS?

    Science.gov (United States)

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan

    2016-09-01

    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Aggressive giant cystic lymphatic malformation in a newborn.

    Science.gov (United States)

    Calış, Mert; Konaş, Ersoy; Takcı, Şahin; Yurdakök, Murat; Tunçbilek, Gökhan

    2013-01-01

    Lymphatic malformations are uncommon, benign and congenital malformations of the lymphatic system exhibiting lack of development of communication between the lymphatic and venous circulation. We report the unusual case of rapidly expanding giant lymphatic malformation of the torso, bilateral axillae and left upper extremity of a newborn. As the first-line treatment, aspiration and sclerotherapy with bleomycin were performed. The sclerotherapy failed to cause regression of the mass, and rapid expansion of the malformation necessitated surgery. Partial resection of the mass was performed. Clinical symptoms of respiratory distress resolved in the early postoperative period, and the patient became hemodynamically stable. However, intrathoracic invasion of the mass developed, leading to restriction of thoracic expansion, ending in death. In conclusion, surgical treatment of giant lymphatic malformations remains challenging.

  5. Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia

    Science.gov (United States)

    Hodge, Lisa M.

    2012-01-01

    Pneumonia is a common cause of morbidity and mortality worldwide. While antibiotics are generally effective for the treatment of infection, the emergence of resistant strains of bacteria threatens their success. The osteopathic medical profession has designed a set of manipulative techniques called lymphatic pump techniques (LPT), to enhance the flow of lymph through the lymphatic system. Clinically, LPT is used to treat infection and oedemaand might be an effective adjuvant therapy in patients with pneumonia.The immune system uses the lymphatic and blood systems to survey to rid the body of pathogens; however, only recently have the effects of LPT on the lymphatic and immune systems been investigated. This short review highlightsclinical and basic science research studies that support the use of LPT to enhance the lymphatic and immune systems and treat pneumonia, and discusses the potential mechanisms by which LPT benefits patients with pneumonia. PMID:22977459

  6. Lymphatic Reprogramming by Kaposi Sarcoma Herpes Virus Promotes the Oncogenic Activity of the Virus-Encoded G-protein Coupled Receptor

    Science.gov (United States)

    Aguilar, Berenice; Choi, Inho; Choi, Dongwon; Chung, Hee Kyoung; Lee, Sunju; Yoo, Jaehyuk; Lee, Yong Suk; Maeng, Yong Sun; Lee, Ha Neul; Park, Eunkyung; Kim, Kyu Eui; Kim, Nam Yoon; Baik, Jae Myung; Jung, Jae U.; Koh, Chester J.; Hong, Young-Kwon

    2012-01-01

    Kaposi sarcoma (KS), the most common cancer in HIV-positive individuals, is caused by endothelial transformation mediated by the KS herpes virus (KSHV)-encoded G-protein coupled receptor (vGPCR). Infection of blood vascular endothelial cells (BECs) by KSHV reactivates an otherwise silenced embryonic program of lymphatic differentiation. Thus, KS tumors express numerous lymphatic endothelial cell (LEC)-signature genes. A key unanswered question is how lymphatic reprogramming by the virus promotes tumorigenesis leading to KS formation. In this study, we present evidence that this process creates an environment needed to license the oncogenic activity of vGPCR. We found that the G-protein regulator RGS4 is an inhibitor of vGPCR that is expressed in BECs, but not in LECs. RGS4 was downregulated by the master regulator of LEC differentiation PROX1, which is upregulated by KSHV and directs KSHV-induced lymphatic reprogramming. Moreover, we found that KSHV upregulates the nuclear receptor LRH1, which physically interacts with PROX1 and synergizes with it to mediate repression of RGS4 expression. Mechanistic investigations revealed that RGS4 reduced vGPCR-enhanced cell proliferation, migration, VEGF expression and Akt activation and to suppress tumor formation induced by vGPCR. Our findings resolve long-standing questions about the pathological impact of KSHV-induced reprogramming of host cell identity, and they offer biological and mechanistic insights supporting the hypothesis that a lymphatic microenvironment is more favorable for KS tumorigenesis. PMID:22942256

  7. 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.

  8. Tissue contribution to the mechanical features of diaphragmatic initial lymphatics.

    Science.gov (United States)

    Moriondo, Andrea; Boschetti, Federica; Bianchin, Francesca; Lattanzio, Simone; Marcozzi, Cristiana; Negrini, Daniela

    2010-10-15

    The role of the mechanical properties of the initial lymphatic wall and of the surrounding tissue in supporting lymph formation and/or progression was studied in six anaesthetized, neuromuscularly blocked and mechanically ventilated rats. After mid-sternal thoracotomy, submesothelial initial lymphatics were identified on the pleural diaphragmatic surface through stereomicroscopy. An 'in vivo' lymphatic segment was prepared by securing two surgical threads around the vessel at a distance of ∼2.5 mm leaving the vessel in place. Two glass micropipettes were inserted into the lumen, one for intraluminar injections of 4.6 nl saline boluses and one for hydraulic pressure (Plymph) recording. The compliance of the vessel wall (Clymph) was calculated as the slope of the plot describing the change in segment volume as a function of the post-injection Plymph changes. Two superficial lymphatic vessel populations with a significantly different Clymph (6.7 ± 1.6 and 1.5 ± 0.4 nl mmHg−1 (mean ± S.E.M.), P < 0.001) were identified. In seven additional rats, the average elastic modulus of diaphragmatic tissue strips was determined by uniaxial tension tests to be 1.7 ± 0.3 MPa. Clymph calculated for an initial lymphatic completely surrounded by isotropic tissue was 0.068 nl mmHg−1, i.e. two orders of magnitude lower than in submesothelial lymphatics. Modelling of stress distribution in the lymphatic wall suggests that compliant vessels may act as reservoirs accommodating large absorbed fluid volumes, while lymphatics with stiffer walls serve to propel fluid through the lumen of the lymphatic vessel by taking advantage of the more efficient mechanical transmission of tissue stresses to the lymphatic lumen.

  9. [Study on distribution and drainage of lymphatic vessels of tongue].

    Science.gov (United States)

    Han, Xin-guang; Li, Jin-rong; Pi, Xin

    2005-10-01

    To investigate the distribution and drainage of lymphatic vessels of tongue, and to provide anatomical evidence for treatment of tongue cancer. Indirect lymphatic injection was employed, combined with clearing method with winter green oil and corrosive cast technique, to study the distribution of lymphatic vessels of tongue. Anatomical methods were used to detect the sentinel lymph nodes in different region of tongue. The lymphatic vessels of dorsal mucosa composed of lymphocapillary vessels and anstomosing side branches were present by superficial and deep capillary networks. The distribution of lymphatic networks extend from tip to base and from one board to another, and was not influenced by the sulcus tenninalis and median lingual sulcus. Lymphatic vessels in the muscular portion communicated with lymphocapillary network of dorsal and ventral mucosa, which made the lymphatic vessels of tongue to be an integrity network structure. These characters of distribution influenced the lymphatic drainage of tongue. The results showed principal sentinel lymph nodes (SLNs) for anterior part of tongue were submental lymph nodes, submandibular lymph nodes and juguloomohyoid lymph nodes, for lateral part and middle part of tongue were submandibular lymph nodes, jugulodigastric lymph nodes and thyroid lymph nodes, and for root part of tongue were jugulodigastric lymph nodes. SLNs for every injection region were all presented at bilatral neck, but the frequency of stained SLNs at homolateral neck was more than that at contralateral neck. The lymphatic vessels of tongue arranged like a network, which made the lymphatic drainage at various ways and made the distribution of sentinel lymph nodes to be bilateral and dispersive.

  10. Zebrafish prox1b Mutants Develop a Lymphatic Vasculature, and prox1b Does Not Specifically Mark Lymphatic Endothelial Cells

    NARCIS (Netherlands)

    Tao, S.; de Witte, M.; Bryson-Richardson, R.J.; Currie, P.D.; Hogan, B.M.; Schulte-Merker, S.

    2011-01-01

    BACKGROUND: The expression of the Prospero homeodomain transcription factor (Prox1) in a subset of cardinal venous cells specifies the lymphatic lineage in mice. Prox1 is also indispensible for the maintenance of lymphatic cell fate, and is therefore considered a master control gene for

  11. Zebrafish prox1b Mutants Develop a Lymphatic Vasculature, and prox1b Does Not Specifically Mark Lymphatic Endothelial Cells

    NARCIS (Netherlands)

    Tao, S.J.; Witte, M.; Bryson-Richardson, R.J.; Currie, P.D.; Hogan, B.M.; Schulte-Merker, S.

    2011-01-01

    Background: The expression of the Prospero homeodomain transcription factor (Prox1) in a subset of cardinal venous cells specifies the lymphatic lineage in mice. Prox1 is also indispensible for the maintenance of lymphatic cell fate, and is therefore considered a master control gene for

  12. EXPERIMENTAL NEPHRITIS IN THE FROG : IV. THE SIGNIFICANCE OF THE FUNCTIONAL RESPONSE TO VASCULAR AND TO PARENCHYMAL DISTURBANCES IN THE KIDNEY.

    Science.gov (United States)

    Oliver, J

    1932-01-31

    parenchymal disturbances was used in low enough concentration to produce only the less complex of the structural alterations that may follow its contact with the cells. And for the same reasons the simplicity of the general conditions existing in the perfusion experiments deserves special emphasis. Every element of the circulating fluid that is going to the kidneys is known and may be varied at will. Every constituent of the urine formed from this fluid can be accurately determined and compared with its condition in the circulating fluid. We have given in our experiments only rates of excretion but "concentration factors," "ratios," "clearances" or any other formulae might be calculated, without altering the conclusion that the functional status of the organs in the two types of damage, vascular and parenchymal, was identical. All these contrasts between the simplicity of our experiments and the complexity that must obtain when the problem is investigated in the living animal, particularly if mammals are used whose renal activity is only partially understood, add considerable weight to the conclusion that functional examination is unable to differentiate between two types of damage of very different significance, the one vascular, transient and reversible, the other parenchymal, permanent and, as far as the cells involved are concerned, irreparable. It might seem that a similar result is the proper conclusion to be drawn from the long series of similar attempts by clinical and experimental study to determine the condition of the kidneys from functional examinations. But it has been and apparently still is hoped, perhaps because in such examinations relations are so complex and involved that nothing seems beyond hope, that some refinement in method or the use of some selectively excreted substance, such as a dye or other foreign substance, may distinguish between the two conditions of vascular and parenchymal disturbance. The answer of our experiments is that the apparent

  13. Intraoperative lymphatic mapping techniques for endometrial cancer.

    Science.gov (United States)

    Mais, Valerio; Cirronis, Maria Giuseppina; Piras, Bruno; Silvetti, Enrico; Cossu, Ester; Melis, Gian Benedetto

    2011-01-01

    Endometrial cancer is the most common malignancy of the female genital tract in developed countries. The primary treatment for women with endometrial cancer is surgical, as well as the staging of the pathological spread pattern of this carcinoma outside of the uterus. A complete surgical staging should include both pelvic and para-aortic lymphadenectomy. The vast majority of endometrial cancers are diagnosed at a very early stage owing to the early presentation as abnormal uterine bleeding. In women with early-stage endometrial cancer the systematic pelvic and para-aortic lymphadenectomy may produce additional morbidity without the benefit of appropriate surgical staging. The procedure of sentinel lymph node (SLN) biopsy after lymphatic mapping has been introduced for patients with cancers of various organs in an effort to avoid complete systematic lymphadenectomy whenever possible. In the case of gynecological malignancies, the reliability of the SLN detection procedure has been extensively investigated in vulvar and cervical cancer. This article focuses on the peculiar aspects of intraoperative lymphatic mapping techniques and SLN procedures in endometrial cancer.

  14. The Lymphatic Malformation Function (LMF) Instrument.

    Science.gov (United States)

    Kirkham, Erin M; Edwards, Todd C; Weaver, Edward M; Balakrishnan, Karthik; Perkins, Jonathan A

    2015-10-01

    The Lymphatic Malformation Function (LMF) instrument is a preliminary parent-report assessment designed to measure outcomes in children with cervicofacial lymphatic malformation (LM). This study aimed to assess the measurement properties of the LMF, refine it, test criterion validity, and evaluate the test-retest reliability. Cross-sectional. Two pediatric tertiary referral centers. Parents of 60 children from 6 months to 15 years old with cervicofacial LM. Parents were recruited via mail and online. The LMF was administered on paper or online initially and again within 21 days. Response distributions and interitem correlations were examined for item reduction. Exploratory factor analysis was conducted on retained items. Cronbach's α, Spearman correlation, and intraclass correlation (ICC) coefficients were calculated to test internal consistency, criterion validity (compared to stage), and test-retest reliability, respectively. One item was removed due to a floor effect. The response scale was collapsed from a 5-point scale to a 3-point scale due to skewness. Six items were discarded due to redundancy (interitem correlations >0.7); 2 items were discarded due to factor loadings 0.80 and <0.90), significant association with stage (P < .05), and good overall test-retest reliability (ICC, 0.82). The LMF has been refined into a 12-item, 2-domain instrument measuring LM-specific signs and impacts with internal consistency, criterion validity, and test-retest reliability. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  15. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis.

    Science.gov (United States)

    Secchin, Pedro; Trope, Beatriz Moritz; Fernandes, Larissa Araujo; Barreiros, Glória; Ramos-E-Silva, Marcia

    2017-01-01

    Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis), it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.

  16. Lipopolysaccharide modulates neutrophil recruitment and macrophage polarization on lymphatic vessels and impairs lymphatic function in rat mesentery.

    Science.gov (United States)

    Chakraborty, Sanjukta; Zawieja, Scott D; Wang, Wei; Lee, Yang; Wang, Yuan J; von der Weid, Pierre-Yves; Zawieja, David C; Muthuchamy, Mariappan

    2015-12-15

    Impairment of the lymphatic system is apparent in multiple inflammatory pathologies connected to elevated endotoxins such as LPS. However, the direct mechanisms by which LPS influences the lymphatic contractility are not well understood. We hypothesized that a dynamic modulation of innate immune cell populations in mesentery under inflammatory conditions perturbs tissue cytokine/chemokine homeostasis and subsequently influences lymphatic function. We used rats that were intraperitoneally injected with LPS (10 mg/kg) to determine the changes in the profiles of innate immune cells in the mesentery and in the stretch-mediated contractile responses of isolated lymphatic preparations. Results demonstrated a reduction in the phasic contractile activity of mesenteric lymphatic vessels from LPS-injected rats and a severe impairment of lymphatic pump function and flow. There was a significant reduction in the number of neutrophils and an increase in monocytes/macrophages present on the lymphatic vessels and in the clear mesentery of the LPS group. This population of monocytes and macrophages established a robust M2 phenotype, with the majority showing high expression of CD163 and CD206. Several cytokines and chemoattractants for neutrophils and macrophages were significantly changed in the mesentery of LPS-injected rats. Treatment of lymphatic muscle cells (LMCs) with LPS showed significant changes in the expression of adhesion molecules, VCAM1, ICAM1, CXCR2, and galectin-9. LPS-TLR4-mediated regulation of pAKT, pERK pI-κB, and pMLC20 in LMCs promoted both contractile and inflammatory pathways. Thus, our data provide the first evidence connecting the dynamic changes in innate immune cells on or near the lymphatics and complex cytokine milieu during inflammation with lymphatic dysfunction. Copyright © 2015 the American Physiological Society.

  17. Sex Differences in Immunology: More Severe Development of Experimental Pulmonary Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor Blockade

    Directory of Open Access Journals (Sweden)

    Julien Guihaire

    2015-01-01

    Full Text Available Background. The epidemiology of pulmonary hypertension (PH is characterized by a female preponderance, whereas males share higher severity of the disease. Objective. To compare the severity of experimental PH between male and female athymic rats. Methods. PH was induced in 11 male and 11 female athymic rats (resp., SU_M and SU_F groups using an inhibitor of VEGF-receptors I and II, semaxanib (40 mg/kg. After 28 days, right ventricular (RV remodeling, systolic function, and hemodynamics were measured using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV myocardium were performed. Results. Four weeks after semaxanib injection, RV end-systolic pressure was higher in SU_M than in SU_F. Males developed marked RV enlargement and systolic dysfunction compared to females. Impairment of RV-PA coupling efficiency was observed only in SU_M. The smooth muscle cells of the pulmonary arteries switched from a contractile state to a dedifferentiated state only in males. Conclusions. Female athymic rats were protected against the development of severe PH. RV-PA coupling was preserved in females through limitation of pulmonary artery muscularization. Control of smooth muscle cells plasticity may be a promising therapeutic approach to reverse established vascular remodeling in PH patients.

  18. I. THE PERMEABILITY OF THE WALL OF THE LYMPHATIC CAPILLARY.

    Science.gov (United States)

    Hudack, S; McMaster, P D

    1932-07-31

    A technique has been developed for the demonstration of lymphatic capillaries in the ear of the mouse by means of vital dyes and for tests of their permeability under normal and pathological conditions. The lymphatics become visible as closed channels from which the dyes escape secondarily into the tissue. Some of them, cross-connections, with extremely narrow lumen, would seem ordinarily not to be utilized. There is active flow along the lymphatics of the mouse ear under ordinary circumstances. The movement of dye was always toward the main collecting system. The valves of the lymphatics as well as fluid flow prevented distal spread. There was in addition slow migration, apparently interstitial in character, but in the same general direction, of dots of color produced by the local injection of dye. The normal permeability of the lymphatics was studied with dyes of graded diffusibility. Their walls proved readily permeable for those highly diffusible pigments that the blood capillaries let through easily, but retained those that the latter retained. Finely particulate matter (India ink, "Hydrokollag"), they did not let pass. No gradient of permeability was observed to exist along them such as exists along the blood capillaries of certain organs. The observed phenomena of lymphatic permeability, like those of the permeability of the blood capillaries, can be explained on the assumption that the lymphatic wall behaves like a semipermeable membrane.

  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. Diaphragmatic lymphatic vessel behavior during local skeletal muscle contraction.

    Science.gov (United States)

    Moriondo, Andrea; Solari, Eleonora; Marcozzi, Cristiana; Negrini, Daniela

    2015-02-01

    The mechanism through which the stresses developed in the diaphragmatic tissue during skeletal muscle contraction sustain local lymphatic function was studied in 10 deeply anesthetized, tracheotomized adult Wistar rats whose diaphragm was exposed after thoracotomy. To evaluate the direct effect of skeletal muscle contraction on the hydraulic intraluminal lymphatic pressures (Plymph) and lymphatic vessel geometry, the maximal contraction of diaphragmatic fibers adjacent to a lymphatic vessel was elicited by injection of 9.2 nl of 1 M KCl solution among diaphragmatic fibers while Plymph was recorded through micropuncture and vessel geometry via stereomicroscopy video recording. In lymphatics oriented perpendicularly to the longitudinal axis of muscle fibers and located at 900 μm from the vessel, Dmc enlarged to 131.1 ± 2.3% of Drest. In vessels parallel to muscle fibers, Dmc increased to 122.8 ± 2.9% of Drest. During contraction, Plymph decreased as much as 22.5 ± 2.6 cmH2O in all submesothelial superficial vessels, whereas it increased by 10.7 ± 5.1 cmH2O in deeper vessels running perpendicular to contracting muscle fibers. Hence, the three-dimensional arrangement of the diaphragmatic lymphatic network seems to be finalized to efficiently exploit the stresses exerted by muscle fibers during the contracting inspiratory phase to promote lymph formation in superficial submesothelial lymphatics and its further propulsion in deeper intramuscular vessels. Copyright © 2015 the American Physiological Society.

  1. Lymphatic vessels regulate immune microenvironments in human and murine melanoma.

    Science.gov (United States)

    Lund, Amanda W; Wagner, Marek; Fankhauser, Manuel; Steinskog, Eli S; Broggi, Maria A; Spranger, Stefani; Gajewski, Thomas F; Alitalo, Kari; Eikesdal, Hans P; Wiig, Helge; Swartz, Melody A

    2016-09-01

    Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment.

  2. Vasa vasorum of superficial collecting lymphatics of human thigh.

    Science.gov (United States)

    Aglianò, M; Sacchi, G; Weber, E; Pucci, A M; Comparini, L

    1997-09-01

    Collecting lymphatics were obtained from human thigh fat for light microscopy and tridimensional reconstruction at time of operation for varicose veins. No patient had lymphedema and routine sections showed no inflammation or notable pathologic alteration of the surrounding soft tissue. Abundant vasa vasorum was observed around the musculature of superficial collecting lymphatics of human thigh. Within intervalvular portions of the lymphatic collectors where the muscle coat was thicker and more compact, the vasa vasorum penetrated between smooth muscle cells and was in contact with the endothelium. In valvular portions of the collecting lymphatics where the muscle layer was thinner and more fragmented, there were fewer vasa vasorum. Tri-dimensional reconstructions of the collecting lymphatic wall showed two communicating plexi of vasa vasorum--one outside and the other inside the muscle layer. Arteries and veins of similar size did not have such an abundant vasa vasorum. The explanation for this difference may relate to the fact that a relatively low oxygen and nutrient content of lymph is insufficient to nourish the collecting lymphatic. Moreover, diffusion of nutrients from the external plexus is likely also impeded by the thickness and density of the muscle layer. The vasa vasorum deep in the muscular layer and in the subendothelial space probably sustain adequate nutrition and oxygenation to the collecting lymphatic.

  3. Primary Intestinal Lymphangiectasia and its Association With Generalized Lymphatic Anomaly

    Directory of Open Access Journals (Sweden)

    Victoria María Díaz Marugán

    2016-01-01

    Full Text Available Background: Lymph is a fluid originating in the interstitial spaces of the body that contains cells, proteins, particles, chylomicrons, and sometimes bacteria. Objectives: The aim of the present study is to demonstrate that primary intestinal lymphangiectasia (PIL results from a disruption of lymphatic circulation, thus corresponding to a secondary rather than a primary event in the context of generalized lymphatic anomaly. Materials and Methods: In this case series and record review, an analysis of intestinal lymphatic involvement was performed on patients diagnosed with PIL between 1965 and 2013. Of the 21 patients included in the study, 10 had been diagnosed before 5 years of age (1 prenatal, 8 between 5 and 18 years of age, and 3 while older than 18 years of age. The follow-up period varied between 1 and 34 years. Clinical data, blood and fecal parameters, imaging studies, endoscopy results, biopsy analyses, treatment details, and outcome information were collected from medical records. Endoscopy, histological studies, magnetic resonance imaging, and lymphoscintigraphy were performed on all patients. Dynamic intranodal lymphangiography was performed on 8 patients. Results: Central lymphatic channel obstruction was identified in 12 patients (57%. Associated lymphatic malformation (LM was present in 16, diarrhea in 10, chylothorax in 11, chylous ascites in 10, pericardial effusion in 6, coagulopathy in 3, and osteolysis in 7. Conclusions: We consider intestinal lymphangiectasia not as an entity in itself, but as a consequence of lymphatic flow impairment in the thoracic duct, producing chylous reflux into the intestinal lymphatics.

  4. Pump function curve shape for a model lymphatic vessel.

    Science.gov (United States)

    Bertram, C D; Macaskill, C; Moore, J E

    2016-07-01

    The transport capacity of a contractile segment of lymphatic vessel is defined by its pump function curve relating mean flow-rate and adverse pressure difference. Numerous system characteristics affect curve shape and the magnitude of the generated flow-rates and pressures. Some cannot be varied experimentally, but their separate and interacting effects can be systematically revealed numerically. This paper explores variations in the rate of change of active tension and the form of the relation between active tension and muscle length, factors not known from experiment to functional precision. Whether the pump function curve bends toward or away from the origin depends partly on the curvature of the passive pressure-diameter relation near zero transmural pressure, but rather more on the form of the relation between active tension and muscle length. A pump function curve bending away from the origin defines a well-performing pump by maximum steady output power. This behaviour is favoured by a length/active-tension relationship which sustains tension at smaller lengths. Such a relationship also favours high peak mechanical efficiency, defined as output power divided by the input power obtained from the lymphangion diameter changes and active-tension time-course. The results highlight the need to pin down experimentally the form of the length/active-tension relationship. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  5. Distribution of the lymphatic vessels in the prostatic fascia.

    Science.gov (United States)

    Soga, Hideo; Takenaka, Atsushi; Murakami, Gen; Haraguchi, Takahiro; Miyake, Hideaki; Tanaka, Kazushi; Fujisawa, Masato

    2011-09-01

    The prostatic fascia-preserving procedure is effective for the early recovery of erectile function after radical prostatectomy; however, the long-term influence of on cancer control was unknown. This study clarified the distribution of lymphatic vessels in the prostatic fascia. The lymphatic vessels were analyzed in 10 prostates obtained from fixed Japanese cadavers (aged, 71-90 years old). Specimens were taken from the apex, the middle part, and the base of the right-hand side of the prostate. Lymphatic vessels were detected by immunohistochemical stain using an antibody specific for the lymphatic endothelial cells (clone D2-40). The lymphatic vessels were counted in the prostate capsule and the prostatic fascia of each section by light microscopy at low power (100×). The median number of lymphatic vessels in the prostatic capsule per prostatic half was 21.0, 14.0, and 21.0 in the apex, middle, and base part of the prostate, respectively. In the prostatic facia the median number of lymphatic vessels per prostatic half was 8.0, 3.0, and 13.0 in the apex, middle, and the base part of the prostate, respectively. In the apex and the middle part the lymphatic vessels in the prostatic fascia were fewer than those in the prostatic capsule. However, in the base part the number of lymphatic vessels in the prostatic fascia was similar to that in the prostatic capsule. The present study suggested the surgeon to pay more attention for the dissection of the fascia at the base of the prostate. Copyright © 2011 Wiley-Liss, Inc.

  6. Facial nerve anatomy, dissection and preservation in lymphatic malformation management.

    Science.gov (United States)

    Lee, Gi Soo; Perkins, Jonathan A; Oliaei, Sepehr; Manning, Scott C

    2008-06-01

    To describe facial nerve anatomy and surgical techniques used for safe lymphatic malformation resection of malformation involving the facial nerve. retrospective case series. tertiary pediatric hospital. record review of lymphatic malformation patients after facial nerve dissection, from 1996 to 2005. Data collected included: facial nerve function, relationship of lymphatic malformation to facial nerve, facial nerve anatomy, dissection extent and clinical outcome. Sixteen patients who met inclusion criteria underwent a total of 21 facial nerve dissections. Mean age at dissection was 48 months (range 1-72 months). Mean follow-up was 38 months (range 8-144 months). Pre-operative lymphatic malformation stage by patient: II=7/16, III=4/16, IV=2/16 and V=3/16. Higher stage lymphatic malformations required more extensive dissections (p=0.026). Pre-operative facial nerve function was House-Brackmann grade (HBG)-1 in 20, and HBG-6 in 1. Eight months postoperatively, facial nerve function was HBG-1 in 18, HBG-2 in 1, and HBG-6 in 2. The facial nerve was surrounded by lymphatic malformation in 10/21, deep to the lymphatic malformation in 5/21, superficial to the lymphatic malformation in 4/21, and not identified in 2/21. Imaging studies predicted facial nerve position in 15/21 procedures. Antegrade nerve dissection was performed in 10/21, retrograde in 7/21 and not done in 2/21. Abnormally elongated facial nerve was identified in 11/21 cases and required more extensive dissection (p=0.040). Facial nerve monitoring was used in 15/21 dissections. Clinical outcomes were felt to be good in 19/21 dissections. In lymphatic malformation surgery, the facial nerve is often abnormally elongated and encompassed by malformation. Pre-operative imaging, facial nerve identification and dissection allow excellent postoperative facial nerve function.

  7. Lymphoscintigraphic evaluation of manual lymphatic therapy: the Godoy & Godoy technique.

    Science.gov (United States)

    de Godoy, José Maria Pereira; Santana, Kleber Roberto; Godoy, Maria de Fátima Guerreiro

    2015-02-01

    The objective of this study was to evaluate the transport of radiotracers in lymphatic collectors during manual lymphatic therapy. The legs of four male and two female patients with leg lymphedema were assessed using lymphoscintigraphy before, during and after manual lymphatic therapy. The ages of the patients, treated in Hospital de Base in Sao Jose do Rio Preto, ranged from 42 to 64 years with a mean age of 51.2 years. Consecutive patients with grade II leg lymphedema were enrolled in this study. Patients with lymphedema secondary to lymphadenectomy, active infections and weight greater than 130  kg were excluded. Patients were submitted to manual lymphatic therapy, which consists of the collapsing of capillaries using manual compression which is then slid along the skin in a stroking action in the direction of the lymph flow within lymphatic vessels towards the lymph nodes. Two dynamic studies were performed; the first was over 40 minutes (3 images every 10 minutes) which was immediately followed by an entire body scan. A second dynamic evaluation was performed taking images at 10-second intervals over 2 minutes during manual lymphatic therapy. To evaluate the displacement of radiotracers, the path of lymphatic collectors from the knee to a lymph node in the upper thigh was divided into five similarly sized regions of interest. The concentration of radiotracer was quantified in each of the regions of interest. The paired t-test was used for statistical analysis with an alpha error of 5% (p value Manual lymphatic therapy improves the transport of radiotracers in lymphatic collectors. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Microcystic Lymphatic Malformation Successfully Treated With Topical Rapamycin.

    Science.gov (United States)

    García-Montero, Pablo; Del Boz, Javier; Sanchez-Martínez, Miguel; Escudero Santos, Isabel María; Baselga, Eulalia

    2017-05-01

    Microcystic lymphatic malformations (MLM) are low-flow vascular malformations composed of multiple small cysts. MLM usually affect deep-lying structures, which makes their treatment even more difficult and complex. A novel and interesting treatment is rapamycin, a mammalian target of rapamycin inhibitor that when orally administrated has offered favorable results. However, until recently, topical rapamycin had not been used in the treatment of MLM. Case 1 is a girl aged 13 years with extensive MLM affecting the muscles in the right buttock. The patient had received frequent cycles of cryotherapy, but they had failed to control the associated symptoms. In the previous 12 months, the patient had reported greater discomfort, swelling, exudate, and superinfection of the affected region. Because no specific treatment has yet been approved for MLM, and as a step before the use of aggressive systemic or intralesional treatments, it was decided to initiate treatment with 1% rapamycin ointment. After 4 months of treatment, the patient presented a marked improvement, with a significant reduction of associated complications and no major side effects. Case 2 is a boy aged 5 years who underwent surgery for an intergluteal lipoblastoma at 3 weeks of life and developed a MLM on the scar 6 months afterward. The lesion showed slow growth and continuous exudation with frequent episodes of superinfection. Treatments with laser multiplex and intralesional bleomycin were performed unsuccessfully. In the previous 4 months, the patient had been treated with 1% rapamycin ointment with significant improvement and no side effects. Copyright © 2017 by the American Academy of Pediatrics.

  9. Musculus gastrocnemius tetanus kinetics in alcohol-intoxicated rats with experimentally-induced hindlimb vascular ischemia under conditions of low-frequence muscle fatigue

    Directory of Open Access Journals (Sweden)

    O. A. Melnychuk

    2014-04-01

    Full Text Available Alcohol intoxication and ischemic injury of skeletal muscles often accompany each other. It is shown that patients hospitalized with chronic alcoholism develop muscle fatigue. Skeletal muscle dysfunction in alcohol-dependent patients is caused by ethanol-associated myofibrillar atrophy and metabolic disbalance, while compression-ischemic lesions result from unconsciousness of the patient, in case of taking the critical alcohol dose. Therefore, the aim of this study is to discover typical m. gastrocnemius (cap. med. tetanic kinetics changes in alcohol intoxicated rats with experimentally induced vascular ischemia of hindlimb muscles under conditions of low-frequency progressive muscle fatigue. Experiments were carried out on 10 young male Wistar rats (149.5 ± 5.8 g kept under standard vivarium conditions and diet. The investigation was conducted in two phases: chronic (30 days and acute (3 hours experiment. All surgical procedures were carried out aseptically under general anesthesia. Ishemic m. gastrocnemius (cap. med. tetanic kinetic changes and force productivity in alcohol intoxicated rats were investigated in the isometric mode, with direct electrical stimulation. The fatigue of m. gastrocnemius (cap. med. was evaluated by three characteristic criteria: the first sag effect, the secondary force rise, the second sag effect. There have been 10 similar experiments: 5 series in each study group with 10 tetanic runs in each series. The highest amplitude of the native m. gastrocnemius (cap. med. tetanus relative to isoline was taken as 100% force response. The same pattern of m. gastrocnemius (cap. med. low-frequency fatigue development was found in both rat groups under study. It is evidenced by the absence of substantial m. gastrocnemius (cap. med. tetanus kinetics differences in alcohol intoxicated rats, compared with non-alcohol intoxicated rats during fatigue test. However, the appreciable m. gastrocnemius (cap. med. tetanic force reduction

  10. Laparoscopic excision of a retroperitoneal lymphatic malformation in a newborn.

    Science.gov (United States)

    Solari, Valeria; Mullassery, Dhanya; Lansdale, Nick; Jesudason, Edwin C

    2011-02-01

    Abdominal lymphatic malformations may be challenging to eradicate. Retroperitoneal lesions may more difficult to resect than mesenteric ones; however, the latter may predispose to intestinal volvulus, leading to calls for their prompt excision. Such lesions identified perinatally may pose particular challenges: in one case, respiratory failure caused by abdominal distension required emergency drainage followed by later laparoscopic excision; laparoscopy has also been used promptly to diagnose and resect neonatal mesenteric lymphatic malformations with their inherent volvulus risk. We illustrate that even if neonatal laparoscopy identifies a retroperitoneal rather than mesenteric lymphatic malformation, curative endosurgical excision remains feasible. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Self-expandable vascular stent covered with polyurethane membrane: an experimental preliminary study of a placement in the thoracic descending aorta of a rabbit using endovascular intervention.

    Science.gov (United States)

    Uematsu, M; Okada, M

    2000-04-01

    The effectiveness of self-expandable vascular endoprosthesis covered with polyurethane membrane for arterial substitution was examined in the descending thoracic aorta of a rabbit, followed by an observation period of 937 days. In this model there was no evidence of thrombus, aneurysmal formation, and/or infection. The self-expandable vascular stent covered with a polyurethane membrane showed long-term patency as well as excellent function, and the histological evaluation revealed endothelial cells covering all of the surface of the endoprosthesis, as was expected. Minimal intimal hyperplasia and no calcifica-tion were demonstrated in any portions. This study suggests that our newly designed self-expandable vascular stent covered with a polyurethane membrane could serve as a satisfactory vascular endoprosthesis with a good long-term patency for substitution. Furthermore, stenting using our model is a safe, simple technique, and an effective treatment for vascular remodeling.

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

    Science.gov (United States)

    Martín, Marta López; Hernández, Miguel A; Avendaño, Cristina; Rodríguez, Francisco; Martínez, Helena

    2011-03-09

    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. 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 garments). 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 attractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image). 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. ClinicalTrials (NCT): NCT01152099.

  13. [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

  14. An investigation of the topography of the lymphatic system of the grey kangaroo (Macropus giganteus). 1. The superficial lymphatic system.

    Science.gov (United States)

    Hopwood, P R

    1988-04-01

    The superficial lymphatic system of the grey kangaroo, Macropus giganteus is described. The description is based on dissections of 130 eastern grey kangaroos. The most significant difference found between the superficial lymphatic drainage pattern of kangaroos and that of the domestic species was the existence of large inguino-axillary lymphatic trunks in the kangaroo. Thus in the kangaroo, instead of lymph passing from the inguinal lymphocentre to the lumbar lymphatic trunks as is the situation in the domestic animals, lymph passes from the inguinal lymphocentre to the axillary lymphocentre. Apart from the lymph draining from the head and ventral neck (which passes to the superficial cervical lymphocentre) and lymph which may pass from the superficial lymphatic vessels to deeper lymphatic vessels, all the superficial lymphatic drainage of the kangaroo passes through the axillary lymphocentre. From the viewpoint of the meat inspection of the carcasses of kangaroos taken as game meat animals, pathology of the axillary lymphocentre may reflect disease in a much wider range of body regions than it would in a domestic animal.

  15. Regional recruitment of rat diaphragmatic lymphatics in response to increased pleural or peritoneal fluid load.

    Science.gov (United States)

    Moriondo, Andrea; Grimaldi, Annalisa; Sciacca, Laura; Guidali, Maria Luisa; Marcozzi, Cristiana; Negrini, Daniela

    2007-03-15

    The specific role of the diaphragmatic tendinous and muscular tissues in sustaining lymph formation and propulsion in the diaphragm was studied in 24 anaesthetized spontaneously breathing supine rats. Three experimental protocols were used: (a) control; (b) peritoneal ascitis, induced through an intraperitoneal injection of 100 ml kg(-1) of iso-oncotic saline; and (c) pleural effusion, induced through an intrapleural injection of 6.6 ml kg(-1) saline solution. A group of animals (n = 12) was instrumented to measure the hydraulic transdiaphragmatic pressure gradient between the pleural and peritoneal cavities in the three protocols. In the other group (n = 12), the injected iso-oncotic saline was enriched with 2% fluorescent dextrans (molecular mass = 70 kDa); at 30 min from the injections these animals were suppressed and their diaphragm excised and processed for confocal microscopy analysis. In control conditions, in spite of a favourable peritoneal-to-pleural pressure gradient, the majority of the tracer absorbed into the diaphragmatic lymphatic system converges towards the deeper collecting lymphatic ducts. This suggests that diaphragmatic lymph formation mostly depends upon pressure gradients developing between the serosal cavities and the lymphatic vessel lumen. In addition, the tracer distributes to lymph vessels located in the muscular diaphragmatic tissue, suggesting that active muscle contraction, rather than passive tendon stretch, more efficiently enhances local diaphragmatic lymph flow. Vice versa, a prevailing recruitment of the lymphatics of the tendinous diaphragmatic regions was observed in peritoneal ascitis and pleural effusion, suggesting a functional adaptation of the diaphragmatic network to increased draining requirements.

  16. Cutaneous Nocardiosis Simulating Cutaneous Lymphatic Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Pedro Secchin

    2017-08-01

    Full Text Available Sporotrichosis is the subcutaneous mycosis caused by several species of the Sporothrix genus. With worldwide occurrence, the State of Rio de Janeiro is presently undergoing a zoonotic sporotrichosis epidemic. The form of lymphocutaneous nocardiosis is rare, being caused especially by Nocardia brasiliensis. It appears as a nodular or ulcerated lesion, with multiple painful erythematous nodules or satellite pustules distributed along the lymphatic tract, similar to the lymphocutaneous variant of sporotrichosis. We present a 61-year-old man who, after an insect bite in the left leg, developed an ulcerated lesion associated with ascending lymphangitis, nonresponsive to previous antibiotic therapies. The patient was admitted for investigation, based on the main diagnostic hypothesis of lymphatic cutaneous sporotrichosis entailed by the highly suggestive morphology, associated with the epidemiologic information that he is a resident of the city of Rio de Janeiro. While culture results were being awaited, the patient was medicated with sulfamethoxazole-trimethoprim to cover CA-MRSA and evolved with total healing of the lesions. After hospital discharge, using an ulcer fragment, an Actinomyces sp. was cultivated and N. brasiliensis was identified by molecular biology. The objective of this report is to demonstrate a case of lymphocutaneous nocardiosis caused by N. brasiliensis after a probable insect bite. Despite the patient being a resident of the State of Rio de Janeiro (endemic region for sporotrichosis, it is highlighted that it is necessary to be aware of the differential diagnoses of an ulcerated lesion with lymphangitis, favoring an early diagnosis and appropriate treatment of the illness.

  17. 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.

  18. [Lymphatics in non-tumoral pulmonary diseases. Review].

    Science.gov (United States)

    Kambouchner, M; Bernaudin, J-F

    2013-06-01

    Whereas lymphatics in pulmonary non-tumoral diseases have been less studied than blood microcirculation, they clearly play a significant role. This review is a short update on lymphatics in various non-tumoral pulmonary diseases, from asthma to interstitial pneumonitis, excluding lymphangioleiomyomatosis. A lymphatic remodelling has been evidenced in asthma as well as in acute or chronic (UIP as NSIP) interstitial lung diseases. Such a remodelling can be explained as a side effect of local changes in fluidics but could also be an active player in the fibrosing process. Moreover the association of juxta-alveloar lymphatics and granulomas provides new insights in the emergence of these lesions in pulmonary sarcoidosis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Lymph node biophysical remodeling is associated with melanoma lymphatic drainage

    National Research Council Canada - National Science Library

    Rohner, Nathan Andrew; McClain, Jacob; Tuell, Sara Lydia; Warner, Alex; Smith, Blair; Yun, Youngho; Mohan, Abhinav; Sushnitha, Manuela; Thomas, Susan Napier

    2015-01-01

    ...) draining the tumor interstitium. Here, we show that lymphatic drainage from murine B16 melanomas in syngeneic, immune-competent C57Bl/6 mice is associated with LN enlargement as well as nonuniform increases in bulk tissue elasticity...

  20. Mesenteric lymphatic malformation associated with acute appendicitis: a case report

    Science.gov (United States)

    2009-01-01

    Introduction Mesenteric lymphatic malformations are rare, benign tumors that are most commonly found in children. The presentation of these tumors is variable and may either be innocuous or life threatening. It has been suggested that mesenteric lymphatic malformations are congenital; however, there is evidence that their growth may be stimulated by local trauma. Case presentation We describe the first case of a mesenteric lymphatic malformation associated with acute appendicitis in a 13-year-old Caucasian boy. The patient is well six months after surgical excision of the tumor. Conclusion The reader should be aware that growth and/or development of mesenteric lymphatic malformations may be associated with trauma and other pro-inflammatory processes. PMID:19918284

  1. Mesenteric lymphatic malformation associated with acute appendicitis: a case report

    Directory of Open Access Journals (Sweden)

    Hunter Catherine

    2009-09-01

    Full Text Available Abstract Introduction Mesenteric lymphatic malformations are rare, benign tumors that are most commonly found in children. The presentation of these tumors is variable and may either be innocuous or life threatening. It has been suggested that mesenteric lymphatic malformations are congenital; however, there is evidence that their growth may be stimulated by local trauma. Case presentation We describe the first case of a mesenteric lymphatic malformation associated with acute appendicitis in a 13-year-old Caucasian boy. The patient is well six months after surgical excision of the tumor. Conclusion The reader should be aware that growth and/or development of mesenteric lymphatic malformations may be associated with trauma and other pro-inflammatory processes.

  2. 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.

  3. Complementary therapeutic effects of dual delivery of insulin-like growth factor-1 and vascular endothelial growth factor by gelatin microspheres in experimental heart failure.

    Science.gov (United States)

    Cittadini, Antonio; Monti, Maria Gaia; Petrillo, Valentina; Esposito, Giovanni; Imparato, Giorgia; Luciani, Alessia; Urciuolo, Francesco; Bobbio, Emanuele; Natale, Carlo F; Saccà, Luigi; Netti, Paolo A

    2011-12-01

    Strategies to prevent adverse left ventricular (LV) remodelling after myocardial infarction have included several traditional approaches and novel cell-based or gene therapies. Delivery of growth factors in post-infarction heart failure has emerged as a valuable alternative strategy. Our aim was to investigate the effects of sequential release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) from biodegradable gelatin microspheres in experimental heart failure. Gelatin hydrogel microspheres were known to guarantee a sustained release of encapsulated growth factors, characterized by an initial burst followed by a slower release. Rats with moderate myocardial infarction were randomized to receive empty microspheres (MI), microspheres loaded with IGF-1 or VEGF, or a combination thereof (DUAL). Myocardial injections of microspheres were performed at the time of surgery, and treatment lasted 4 weeks. Echocardiography, LV catheterization, morphometric histology and immunohistochemistry, and molecular assessment of downstream mediators [e.g. Akt, endothelial nitric oxide synthase (eNOS), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA-2)] were assessed at the end of the treatment period. Infarct sizes were 33 ± 2, 28 ± 4, 24 ± 3, and 16 ± 3% in the MI, IGF-1, VEGF, and DUAL groups, respectively. IGF-1 attenuated LV remodelling, improved LV systolic and diastolic function, increased myocyte size, and reduced apoptotic deaths, capillary loss, and indexes of inflammation. VEGF-treated animals displayed a marked myocardial neoangiogenesis that led to the formation of mature vessels if combined with IGF-1 delivery. Downstream effects of IGF-1 were principally mediated by the Akt-mTOR (mammalian target of rapamycin)-dependent pathway, and both growth factors, particularly VEGF, induced a robust and sustained increase of eNOS. IGF-1 and VEGF exerted complementary therapeutic effects in post-infarction heart failure. Biodegradable

  4. Transactivation of epidermal growth factor receptor in vascular and renal systems in rats with experimental hyperleptinemia: role in leptin-induced hypertension.

    Science.gov (United States)

    Jamroz-Wiśniewska, Anna; Wójcicka, Grazyna; Łowicka, Ewelina; Ksiazek, Marta; Bełtowski, Jerzy

    2008-04-15

    We examined the role of epidermal growth factor (EGF) receptor in the pathogenesis of leptin-induced hypertension in the rat. Leptin, administered in increasing doses (0.1-0.5 mg/kg/day) for 10 days, increased phosphorylation levels of non-receptor tyrosine kinase, c-Src, EGF receptor and extracellular signal-regulated kinases (ERK) in aorta and kidney, which was accompanied by the increase in plasma concentration and urinary excretion of isoprostanes and H2O2. Blood pressure and renal Na+,K+-ATPase activity were higher, whereas urinary sodium excretion was lower in animals receiving leptin. The effects of leptin on renal Na+,K+-ATPase, natriuresis and blood pressure were abolished by NADPH oxidase inhibitor, apocynin, Src kinase inhibitor, PP2, EGF receptor inhibitor, AG1478, protein farnesyltransferase inhibitor, manumycin A, and ERK inhibitor, PD98059. In contrast, inhibitors of insulin-like growth factor-1 and platelet-derived growth factor receptors, AG1024 and AG1295, respectively, only slightly reduced ERK phosphorylation and had no effect on blood pressure in rats receiving leptin. These data indicate that: (1) experimental hyperleptinemia is associated with oxidative stress and c-Src-dependent transactivation of the EGF receptor, which stimulates ERK in vascular wall and the kidney, (2) overactivity of EGF receptor-ERK pathway contributes to leptin-induced hypertension by stimulating renal Na+,K+-ATPase and reducing sodium excretion, (3) inhibitors of c-Src, EGF receptor and ERK may be considered as a novel therapy for hypertension associated with hyperleptinemia, e.g. in patients with obesity and metabolic syndrome.

  5. Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency.

    Science.gov (United States)

    Hos, Deniz; Bukowiecki, Anne; Horstmann, Jens; Bock, Felix; Bucher, Franziska; Heindl, Ludwig M; Siebelmann, Sebastian; Steven, Philipp; Dana, Reza; Eming, Sabine A; Cursiefen, Claus

    2017-08-03

    Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema. Pharmacological blockade of lymphangiogenesis via VEGFR-3 inhibition results in increased corneal thickness due to delayed drainage of corneal edema and a trend towards prolonged corneal opacification. Notably, lymphatics are also detectable in the cornea of a patient with acute edema due to spontaneous Descemet´s (basement) membrane rupture in keratoconus, mimicking this animal model and highlighting the clinical relevance of lymphangiogenesis in corneal fluid homeostasis. Together, our findings provide evidence that lymphangiogenesis plays an unexpectedly beneficial role in the regulation of corneal edema and transparency. This might open new treatment options in blinding diseases associated with corneal edema and transparency loss. Furthermore, we demonstrate for the first time that physiological lymphangiogenesis also occurs in primarily avascular sites.

  6. Colonic mesenteric lymphatic malformation presenting as an intraabdominal abscess in an infant: A case report.

    Science.gov (United States)

    Sriram, Gonakoti; Zendejas, Benjamin; Vargas, Sara O; Chen, Catherine

    2017-08-05

    Lymphatic malformations are low-flow vascular malformations most commonly located in the head and neck; isolated intraabdominal involvement is rare. An 8-month-old previously healthy male presented with a 9-day history of fevers. On examination, right-sided abdominal tenderness was noted. Ultrasound revealed a large heterogeneous mass, and CT scan revealed a rim-enhancing cystic mass adjacent to the right colon. Laboratory investigation including blood cultures was normal. His fever resolved with broad-spectrum antibiotics. Diagnostic laparoscopy revealed a large, firm mass arising from the mesentery of the right colon. An open right hemicolectomy with ileocolonic anastomosis was performed. The infant tolerated the procedure well, and he was discharged home on postoperative day four, pathologic examination identified a mesenteric lymphatic malformation with secondary abscess formation. This atypical presentation of an uncommon entity was instructive in several ways, particularly illustrating the diagnostic pitfalls that can be introduced by superinfection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Emerging lymphatic imaging technologies for mouse and man

    OpenAIRE

    Sevick-Muraca, Eva M.; Kwon, Sunkuk; Rasmussen, John C.

    2014-01-01

    The lymphatic circulatory system has diverse functions in lipid absorption, fluid homeostasis, and immune surveillance and responds dynamically when presented with infection, inflammation, altered hemodynamics, and cancer. Visualization of these dynamic processes in human disease and animal models of disease is key to understanding the contributory role of the lymphatic circulatory system in disease and to devising effective therapeutic strategies. Longitudinal, non-destructive, and repeated ...

  8. [The macrophage contribution for maintaining lymphatic vessel in cornea].

    Science.gov (United States)

    Maruyama, Kazuichi

    2014-11-01

    The presence of antigen-presenting cells and hem- and lymphangiogenesis in the cornea are risk factors for the rejection of corneal transplants. We previously reported that antigen-presenting cells such as macrophages (MPs) play an important role in the induction of lymphatic endothelial cells during inflammation. This prompted us to inquire whether the existence of lymphatic vessels in the cornea is associated with the activation of MPs during inflammation. To investigate this question, we performed suture placement on the cornea to induce inflammation. We found that a large number of MPs were recruited and that lymphatic vessels were formed in response. Next, as C57BL/6 mice have a higher rejection rate after corneal transplantation than BALB/c mice, we compared the corneas of C57BL/6 and BALB/c mice under normal and inflamed conditions. We found that the number of spontaneously formed lymphatic vessels in the C57BL/6 corneas was significantly greater than in the BALB/c corneas, and that there were more activated MPs in the C57BL/6 corneas than in the BALB/c corneas. Additionally, to confirm that activated MPs induced and maintained lymphatic vessels in the cornea, we depleted the number of MPs in C57BL/6 mice via clodronate liposomes. We found that MP depletion reduced the spontaneous formation of lymphatic vessels and reduced inflammation-induced lymphangiogenesis relative to control mice. Finally, we found that mice deficient in MP markers had fewer spontaneously formed lymphatic vessels and less lymphangiogenesis than control C57BL/6 mice. The evidence gathered in this study leads us to conclude that activated MPs appear to play an important role in the formation of new lymphatic vessels and in their maintenance.

  9. Functional arrangement of rat diaphragmatic initial lymphatic network.

    Science.gov (United States)

    Grimaldi, Annalisa; Moriondo, Andrea; Sciacca, Laura; Guidali, Maria Luisa; Tettamanti, Gianluca; Negrini, Daniela

    2006-08-01

    Fluid and solute flux between the pleural and peritoneal cavities, although never documented under physiological conditions, might play a relevant role in pathological conditions associated with the development of ascitis and pleural effusion and/or in the processes of tumor dissemination. To verify whether a pleuroperitoneal flux might take place through the diaphragmatic lymphatic network, the transdiaphragmatic pressure gradient (Delta P(TD)) was measured in five spontaneously breathing anesthetized rats. Delta P(TD) was -1.93 cmH2O (SD 0.59) and -3.1 cmH2O (SD 0.82) at end expiration and at end inspiration, respectively, indicating the existence of a pressure gradient directed from the abdominal to the pleural cavity. Morphometrical analysis of the diaphragmatic lymphatic network was performed in the excised diaphragm of three additional rats euthanized with an anesthesia overdose. Optical and electron microscopy revealed that lymphatic submesothelial lacunae and lymphatic capillaries among the skeletal muscles fibers show the ultrastructural features of the so-called initial lymphatic vessels, namely, a discontinuous basal lamina and anchoring filaments linking the outer surface of the endothelial cells to connective tissue or to muscle fibers. Primary unidirectional valves in the wall of the initial lymphatics allow entrance of serosal fluid into the lymphatic network preventing fluid backflow, while unidirectional intraluminar valves in the transverse vessels convey lymph centripetally toward central collecting ducts. The complexity and anatomical arrangement of the two valves system suggests that, despite the existence of a favorable Delta P(TD), in the physiological condition no fluid bulk flow takes place between the pleural and peritoneal cavity through the diaphragmatic lymphatic network.

  10. Lymphangioma Circumscriptum (Microcystic Lymphatic Malformation): Palliative Coagulation Using Radiofrequency Current

    Science.gov (United States)

    Omprakash HM; Rajendran SC

    2008-01-01

    Lymphangioma circumscriptum (LC, microcystic lymphatic malformation), a hamartomatous lymphatic malformation, is a difficult condition to treat. Different treatments such as surgical excision, lasers, sclerotherapy etc have all been tried with varying success. We report here the efficacy of a radiofrequency current in two patients with lymphangioma circumscriptum. The radiofrequency technique is a safe, economical, and commonly available technique for the treatment of LC; the surgical safety and outcome were satisfactory in our patients. PMID:20300350

  11. Lymphatic Malformation in Adult Patient: A Rare Case

    OpenAIRE

    Shah, G. H.; M. D. Deshpande

    2010-01-01

    Lymphatic malformation is an uncommon anomaly that commonly occurs in the posterior triangles of infants. The case presented here was an adult male patient with swelling in submental region. This site often leads to misdiagnosis of other common pathology including plunging ranula or lipoma. However, USG and MRI were done for diagnosis of the lesion by which final diagnosis of lymphatic malformation was made. Surgical excision was carried out and histopathology confirmed the primary diagnosis....

  12. Lymphangioma Circumscriptum (Microcystic Lymphatic Malformation): Palliative Coagulation Using Radiofrequency Current

    OpenAIRE

    Omprakash HM,; Rajendran SC,

    2008-01-01

    Lymphangioma circumscriptum (LC, microcystic lymphatic malformation), a hamartomatous lymphatic malformation, is a difficult condition to treat. Different treatments such as surgical excision, lasers, sclerotherapy etc have all been tried with varying success. We report here the efficacy of a radiofrequency current in two patients with lymphangioma circumscriptum. The radiofrequency technique is a safe, economical, and commonly available technique for the treatment of LC; the surgical safety ...

  13. Zinc effect on human lymphatic malformation cells in vitro.

    Science.gov (United States)

    O, Teresa Min-Jung; Lou, Man Si; Ma, Yupo

    2016-01-01

    Lymphatic malformations (LM) are clinically characterized by episodes of inflammatory episodes. Often, an upper respiratory illness or trauma will lead to painful swelling in the distribution of the LM. Zinc is an element involved in numerous aspects of cellular metabolism and is a common dietary supplement and cold remedy. We surmise that zinc may act as a therapeutic anti-inflammatory agent for lymphatic malformations and their cellular components. We investigate the apparent cytotoxic effect of zinc ion on lymphatic malformation cells in vitro. Fresh surgical lymphatic malformation specimens from 10 patients were collected and processed in a laboratory. Tissues were processed and lymphatic malformation cells were isolated and grown. Immunohistochemistry and cell morphology were used to confirm LM cells. HUVEC cells were used as controls. Zinc chloride solution was added to the cells and its effect observed. LM cells were isolated from five of the 10 specimens. Of these, the cells of only one specimen were able to be amplified to confluence. Five specimens were contaminated. Immunohistochemical staining (CD31, D2-40, and LYVE-1) and cell morphology of our specimens were consistent with lymphatic malformation while HUVEC control cells were negative. Zinc has a cytotoxic effect on BEL isolates in vitro with no obvious effect on cell morphology or growth rate of the control HUVEC cells. When compared with the published toxic zinc concentration for most cell types in the literature (100μM total zinc in vitro), our result indicates that LM cells may have a lower tolerance to zinc (10μM total zinc in vitro). Zinc has an apparent morphological effect on lymphatic malformation cells in vitro. Compared with other cell types, LM cells have a lower tolerance to zinc. While this result looks very promising for future therapeutic use of zinc in acute lymphangitis, further studies are necessary, such as finding the IC50 of zinc for lymphatic malformation in vitro and also in

  14. Vascular ring

    DEFF Research Database (Denmark)

    Schmidt, Anne Mette S; Larsen, Signe H; Hjortdal, Vibeke E

    2018-01-01

    BACKGROUND: Vascular ring is a rare cause of recurrent respiratory infections, dysphagia and stridor. Surgical repair is considered safe but the long-term outcomes are unclear. The purpose of this study was to investigate the mortality and morbidity following vascular ring surgery in a single...... age of 1.4 years (range 0.008-64 years) were operated for vascular ring. Median follow-up was 6.8 years (range 2.4-34 years). Presenting symptoms were stridor (52%), dysphagia or vomiting (52%) and recurrent respiratory infections (48%). There were no early or late deaths. Three months postoperatively...

  15. [Classification of vascular tumors and malformations: basis for classification and clinical purpose].

    Science.gov (United States)

    Moure, C; Reynaert, G; Lehmman, P; Testelin, S; Devauchelle, B

    2007-06-01

    Vascular anomalies are a complex pathological group. They are especially difficult to study because of confusion in the terminology used. The classification developed by the ISSVA (International Society for the Study of Vascular Anomalies) now allows using a common scientific language. The classification is based on clinical, radiological, hemodynamic, and histological arguments. There are two groups of lesions: vascular tumors and vascular malformations. Vascular tumors are associated to vascular proliferation. They are called hemangioma and can be infantile or congenital. Vascular malformations are associated to vessels with morphologic anomalies. They are classified according to the distorted vessel type, capillary, venous, lymphatic, and arteriovenous). Such a classification has many implications. It is a guide for the orientation of radiological exams and treatment of vascular anomalies. The management of these anomalies is still difficult and must involve an interdisciplinary approach.

  16. The association of adult Onchocerca volvulus with lymphatic vessels.

    Science.gov (United States)

    Mackenzie, C D; Huntington, M K; Wanji, S; Lovato, R V; Eversole, R R; Geary, T G

    2010-02-01

    Immunocytochemical examination of onchocercal nodule tissues containing adult Onchocerca volvulus using immuno-markers for blood and lymphatic vessels (vWF, D2-40, podoplanin, Prox-1, and Lyve1) shows a distinct pattern of distribution of these vessels within nodules. Blood vessels were commonly seen associated with organized lymphoid cellular aggregates in the both the outer and inner areas of the nodules. In contrast, the majority of the lymphatic vessel positivity was seen in the central zone in close apposition to the adult parasites, and the remainder usually associated with microfilariae in the outer areas of the nodule. These findings suggest an intimate relationship between adult O. volvulus and lymphatic vessels, including the likely proliferation of lymphatic endothelial cells (lymphangectasia) akin to that seen with other filariae. These findings indicate that adult O. volvulus may migrate via the lymphatic system, and that clinical manifestations of this disease that involve tissue edema may be the result of the location of these worms in the lymphatic system.

  17. 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.

  18. The passive biomechanics of human pelvic collecting lymphatic vessels.

    Science.gov (United States)

    Athanasiou, Dimitrios; Edgar, Lowell T; Jafarnejad, Mohammad; Nixon, Katherine; Duarte, Delfim; Hawkins, Edwin D; Jamalian, Samira; Cunnea, Paula; Lo Celso, Cristina; Kobayashi, Shunichi; Fotopoulou, Christina; Moore, James E

    2017-01-01

    The lymphatic system has a major significance in the metastatic pathways in women's cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking. Our aim is to characterize, for the first time, the passive biomechanical behavior of human collecting lymphatic vessels removed at pelvic lymph node dissection during primary debulking surgeries for epithelial ovarian cancer. Isolated vessels were cannulated and then pressurized at varying levels of applied axial stretch in a calcium-free Krebs buffer. Pressurized vessels were then imaged using multi-photon microscopy for collagen-elastin structural composition and fiber orientation. Both pressure-diameter and force-elongation responses were highly nonlinear, and axial stretching of the vessel served to decrease diameter at constant pressure. Pressure-diameter behavior for the human vessels is very similar to data from rat mesenteric vessels, though the human vessels were approximately 10× larger than those from rats. Multiphoton microscopy revealed the vessels to be composed of an inner layer of elastin with an outer layer of aligned collagen fibers. This is the first study that successfully described the passive biomechanical response and composition of human lymphatic vessels in patients with ovarian cancer. Future work should expand on this knowledge base with investigations of vessels from other anatomical locations, contractile behavior, and the implications on metastatic cell transport.

  19. Sensitivity analysis of near-infrared functional lymphatic imaging

    Science.gov (United States)

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

    2012-06-01

    Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing. To demonstrate the efficacy of this imaging approach to quantifying immediate functional changes in lymphatics, we investigate the effects of a topically applied nitric oxide (NO) donor glyceryl trinitrate ointment. Premixing ICG with albumin induces greater fluorescence intensity, with the ideal concentration being 150 μg/mL ICG and 60 g/L albumin. ICG fluorescence can be detected at a concentration of 150 μg/mL as deep as 6 mm with our system, but spatial resolution deteriorates below 3 mm, skewing measurements of vessel geometry. NO treatment slows lymphatic transport, which is reflected in increased transport time, reduced packet frequency, reduced packet velocity, and reduced effective contraction length. NIR imaging may be an alternative to invasive procedures measuring lymphatic function in vivo in real time.

  20. Quantum dots trace lymphatic drainage from the mouse eye

    Science.gov (United States)

    Tam, Alex L. C.; Gupta, Neeru; Zhang, Zhexue; Yücel, Yeni H.

    2011-10-01

    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. 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. © 2014 Wiley Periodicals, Inc.

  2. 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.

  3. Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart Disease

    National Research Council Canada - National Science Library

    Dori, Yoav; Keller, Marc S; Rome, Jonathan J; Gillespie, Matthew J; Glatz, Andrew C; Dodds, Kathryn; Goldberg, David J; Goldfarb, Samuel; Rychik, Jack; Itkin, Maxim

    2016-01-01

    ... as a treatment for these patients. METHODS AND RESULTS—This is a retrospective case series of 18 patients with surgically corrected congenital heart disease and plastic bronchitis who presented for lymphatic imaging and intervention...

  4. Vascular anomalies

    Directory of Open Access Journals (Sweden)

    Murthy Jyotsna

    2005-01-01

    Full Text Available Management of vascular anomalies is an emerging multidisciplinary, super-specialisation field involving several surgical, medical and radiological specialties. Over the years, development in this field has been limited because of complex nomenclature and lack of consensus on the best practice for treatment of some of the more complex vascular anomalies. It was only in 1996 that the International Society of the Study of Vascular Anomalies defined nomenclature for the anomalies and gave clear guidelines on management, allowing for improved clinical practices. As in all fields of clinical medicine, the correct diagnosis of the vascular anomalies is essential to choose the appropriate treatment. This paper gives clear guidelines for diagnosis, understanding of the anomalies and discusses their management.

  5. Tie1 is required for lymphatic valve and collecting vessel development

    Science.gov (United States)

    Qu, Xianghu; Zhou, Bin; Baldwin, H. Scott

    2015-01-01

    Tie1 is a receptor tyrosine kinase with broad expression in embryonic endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1 allele resulted in abnormal lymphatic patterning and architecture, decreased lymphatic draining efficiency, and ultimately, embryonic demise. Here we report that Tie1 is present uniformly throughout the lymphatics and from late embryonic/early postnatal stages, becomes more restricted to lymphatic valve regions. To investigate later events of lymphatic development, we employed Cre-loxP recombination utilizing a floxed Tie1 allele and an Nfatc1Cre line, to provide loxP excision predominantly in lymphatic endothelium and developing valves. Interestingly, unlike the early prenatal defects previously described by ubiquitous endothelial deletion, excision of Tie1 with Nfatc1Cre resulted in abnormal lymphatic defects in postnatal mice and was characterized by agenesis of lymphatic valves and a deficiency of collecting lymphatic vessels. Attenuation of Tie1 signaling in lymphatic endothelium prevented initiation of lymphatic valve specification by Prox1 high expression lymphatic endothelial cells that is associated with the onset of turbulent flow in the lymphatic circulation. Our findings reveal a fundamental role for Tie signaling during lymphatic vessel remodeling and valve morphogenesis and implicate it as a candidate gene involved in primary lymphedema. PMID:25576926

  6. Mechanisms of VIP-induced inhibition of the lymphatic vessel pump.

    Science.gov (United States)

    von der Weid, Pierre-Yves; Rehal, Sonia; Dyrda, Peter; Lee, Stewart; Mathias, Ryan; Rahman, Mozibur; Roizes, Simon; Imtiaz, Mohammad S

    2012-06-01

    Lymphatic vessels serve as a route by which interstitial fluid, protein and other macromolecules are returned to the blood circulation and immune cells and antigens gain access to lymph nodes. Lymph flow is an active process promoted by rhythmical contraction-relaxation events occurring in the collecting lymphatic vessels. This lymphatic pumping is an intrinsic property of the lymphatic muscles in the vessel wall and consequent to action potentials. Compromised lymphatic pumping may affect lymph and immune cell transport, an action which could be particularly detrimental during inflammation. Importantly, many inflammatory mediators alter lymphatic pumping. Vasoactive intestinal peptide (VIP) is a neuro- and immuno-modulator thought to be released by nerve terminals and immune cells in close proximity to lymphatic vessels. We demonstrated the presence of the peptide in lymphatic vessels and in the lymph and examined the effects of VIP on mesenteric collecting lymphatic vessels of the guinea pig using pharmacological bioassays, intracellular microelectrode electrophysiology, immunofluorescence and quantitative real-time PCR. We showed that VIP alters lymphatic pumping by decreasing the frequency of lymphatic contractions and hyperpolarizing the lymphatic muscle membrane potential in a concentration-dependent manner. Our data further suggest that these effects are mainly mediated by stimulation of the VIP receptor VPAC2 located on the lymphatic muscle and the downstream involvement of protein kinase A (PKA) and ATP-sensitive K⁺ (KATP) channels. Inhibition of lymphatic pumping by VIP may compromise lymph drainage, oedema resolution and immune cell trafficking to the draining lymph nodes.

  7. 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.

  8. Vascular Dementia

    OpenAIRE

    Maria Alekseyevna Cherdak; O V Uspenskaya

    2015-01-01

    This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)00463-8 Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the e...

  9. Vascular Vertigo

    Directory of Open Access Journals (Sweden)

    Mazyar Hashemilar

    2017-02-01

    Full Text Available 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 vertigo. Vertigo is an illusion of movement caused by asymmetrical involvement of the vestibular system by various causes. Migraine is the most frequent vascular disorder that causes vertigo in all age groups. Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders are rare in the general population, but vertigo may be seen in almost up to 50% of patients with different vasculitic syndromes. Conclusions: Migraine, cerebrovascular disorders especially involving the vertebrobasilar territory, cardiocirculatory diseases, neurovascular compression of the eighth nerve, and vasculitis are vascular causes of vertigo syndromes.

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

    Directory of Open Access Journals (Sweden)

    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. Venous anastomosis procedure for treatment of lymphatic malformation in Klippel-Trenaunay syndrome

    Directory of Open Access Journals (Sweden)

    Motoi Kato, M.D.

    2017-05-01

    We previously reported that lymphatic venous anastomosis (LVA may be a safe and effective procedure for reducing the size of micro cystic type LM by decreasing the intra cystic lymph [3]. We treated a case of KTS in a 9-year-old boy who had improvement of lower abdominal swelling and penile pain after a single LVA. The method involved is to make a bypass, from the afferent lymph-collecting vessel to subcutaneous veins. However, to apply LVA to LM, it is sometimes problematic to detect the afferent flow in combined vascular malformations, such as KTS. Therefore, we performed VA making a bypass directly from LM, instead. We classify two types of LVA methods for LM: afferent lymph vessel LMVA (A-LMVA, and sidewall LMVA (S-LMVA. S-LMVA has more merits than the previously reported A-LMVA.

  12. 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.

  13. Primary lymphoedema and lymphatic malformation: are they the two sides of the same coin?

    Science.gov (United States)

    Lee, B B; Villavicencio, J L

    2010-05-01

    To clear the confusion regarding the relationship between the 'primary lymphoedema' and (truncular) lymphatic malformation (LM); the latter is one of congenital vascular malformations. A literature review was carried out on the primary lymphoedema either existing as an independent LM lesion or as a component of the Klippel-Trenaunay syndrome. The review was able to provide a contemporary guide/conclusion on the definition and classification, clinical evaluation and clinical management regarding conservative (physical) therapy, reconstructive surgical therapy and ablative/excisional surgical therapy, for the primary lymphoedema as an LM. Primary lymphoedema can be considered as 'congenital' since its majority represents a clinical manifestation of the truncular type of LM arising during the later stages of lymphangiogenesis. Such embryological staging information of the LM is critical for proper management of the primary lymphoedema when it exists with other congenital vascular malformations (Klippel-Trenaunay syndrome). 2. Basic non-invasive to minimally invasive tests will provide an adequate diagnosis and lead to the correct multidisciplinary, specifically targeted and sequenced treatment strategy. 3. The mainstay of current management of the primary lymphoedema/truncular LM is complex decongestive therapy; and the reconstructive as well as ablative surgical therapy remain adjunctive therapies at best. Copyright (c) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Vascular Access Procedures

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Vascular Access Procedures A vascular access procedure inserts a flexible, ... the limitations of Vascular Access Procedures? What are Vascular Access Procedures? A vascular access procedure involves the insertion ...

  15. Vascular Access for Hemodialysis

    Science.gov (United States)

    ... Adequacy Eating & Nutrition for Hemodialysis Vascular Access for Hemodialysis What is a vascular access? A vascular access ... Set Up the Vascular Access Well before Starting Hemodialysis Patients should set up a vascular access well ...

  16. What Is Vascular Disease?

    Science.gov (United States)

    ... Policy What Is Vascular Disease? What Is Vascular Disease? Vascular disease is any abnormal condition of the blood ... Privacy Policy × Your ticket for the: What Is Vascular Disease? Title What Is Vascular Disease? USD Close Print

  17. Case series on vascular malformation and their review with regard to terminology and categorization

    Directory of Open Access Journals (Sweden)

    Devi Charan Shetty

    2010-01-01

    Full Text Available Malformations of vascular nature originate as anomalies caused due to errors in vasculogenesis. These tumors are generally broadly classified into vascular tumors (hemangiomas and vascular malformations (venous malformations, arteriovenous malformations, lymphatic malformations. These descriptive tumors and malformations have been categorized based on the architectural assembly of vessels. Lymphangiomas are further subclassified microscopically into capillary, cavernous, cystic and lymphangioendothelioma, depending upon their histopathological features. Lymphatic malformations or lymphangiomas are uncommon congenital malformations of the lymphatic system, usually occurring in the head and neck region, characterized by collections of ectatic lymph vessels that form endothelial lined cystic spaces. Advancements in the knowledge of pathogenesis of such vascular malformations are continuously changing their treatment protocols. Early recognition is of utmost importance for initiation of proper treatment and avoiding serious complications. Hemangiolymphangioma is a variant of lymphangioma showing vascular component. Herewith, we present a case of vascular malformation diagnosed as hemangiolymphangioma histopathologically in a 9-year-old girl, along with a review of literature regarding its categorization.

  18. Assessing lymphatic response to treatments in head and neck cancer using near-infrared fluorescence imaging

    Science.gov (United States)

    Tan, I.-Chih; Karni, Ron J.; Rasmussen, John C.; Sevick-Muraca, Eva M.

    2014-05-01

    Care for head and neck (HN) cancer could be improved with better mapping of lymphatic drainage pathways in HN region as well as understanding the effect of the cancer treatments on lymphatics. In this study, near-infrared fluorescence imaging is being used to visualize the lymphatics in human subjects diagnosed with HN cancer before and after treatments. Imaging results show the lymphatic architecture and contractile function in HN. Reformation of lymphatics during the course of cancer care was also seen in the longitudinal imaging. This allows us to better understand the lymphatics in HN cancer patients.

  19. [Abdominal lymphatic malformation (ALM). Our experience].

    Science.gov (United States)

    López López, A J; Gómez Farpón, A; Vega Mata, N; Montalvo Avalos, C; Oviedo Gutiérrez, M; Granell Suárez, C; Alvarez Muñoz, V; Alvarez Zapico, J A

    2013-01-01

    Lymphatic malformations are congenital lesions usually placed in the head and neck, the abdominal location is infrequent. Analyze our experience in ALM management. Retrospective study of pediatric patients with ALM from 1996 to 2011. It is a descriptive analysis of clinical, diagnostic and therapeutic features. 10 patients with ALM were treated (6 girls: 4 boys), with a median age of 4.03 years (3 days-13 years). Acute abdomen was the most common presenting feature (40%). Ultrasound was carried out in all these cases, completing the study with CT (9 cases), MRI (1) or both (1). Treatment was surgical, excepting one case that presented infection of the ALM. The approach by laparotomy allowed total resection in all cases, involving bowel resection in 6. The mass was located in small bowel mesentery (6), mesocolon (1), liver (1), and in retroperitoneum (1). The final pathologic diagnosis showed an error in diagnostic imaging of 60%.The mean follow-up was 18 months (SD: 12.8), with not recurrences. ALM often manifests in a non-specific form and it may remain silent. Imaging studies guide the diagnosis, but only the histology provides a definitive result. Total resection is the best option to prevent recurrences and minimize complications.

  20. Vascular dementia.

    Science.gov (United States)

    O'Brien, John T; Thomas, Alan

    2015-10-24

    Vascular dementia is one of the most common causes of dementia after Alzheimer's disease, causing around 15% of cases. However, unlike Alzheimer's disease, there are no licensed treatments for vascular dementia. Progress in the specialty has been difficult because of uncertainties over disease classification and diagnostic criteria, controversy over the exact nature of the relation between cerebrovascular pathology and cognitive impairment, and the paucity of identifiable tractable treatment targets. Although there is an established relation between vascular and degenerative Alzheimer's pathology, the mechanistic link between the two has not yet been identified. This Series paper critiques some of the key areas and controversies, summarises treatment trials so far, and makes suggestions for what progress is needed to advance our understanding of pathogenesis and thus maximise opportunities for the search for new and effective management approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. [Vascular trauma].

    Science.gov (United States)

    Furuya, T; Nobori, M; Tanaka, N

    1999-07-01

    Vascular trauma is essentially acute arterial obstruction, often combined with hemorrhage, fracture, and infection. It can be both life-threatening and limb-threatening and needs an emergency operation. In vascular trauma patient, multiple fracture and organ injury, such as brain, lung, liver, spleen, kidney, or gastrointestinal tract should be evaluated to decide treatment priority. When the pulse distal from the injured site is absent or diminished, vascular trauma is most likely and reconstruction should be accomplished within "the golden time (6-8 hours)". Intimal damage followed by platelet aggregation and thrombus formation will necessitate resection and repair of the site instead of simple thrombectomy. Although autogenous vein is the first choice, artificial graft can be implanted for short segment in non-infected field.

  2. Lymphatic invasion and the Shields index in predicting melanoma metastases.

    Science.gov (United States)

    Špirić, Zorica; Erić, Mirela; Eri, Živka

    2017-11-01

    Findings of the prognostic significance of lymphatic invasion are contradictory. To determine an as efficient cutaneous melanoma metastasis predictor as possible, Shields et al. created a new prognostic index. This study aimed to examine whether the lymphatic invasion analysis and the Shields index calculation can be used in predicting lymph node status in patients with cutaneous melanoma. Lymphatic invasion of 100 melanoma specimens was detected by dual immunohistochemistry staining for the lymphatic endothelial marker D2-40 and melanoma cell S-100 protein. The Shields index was calculated as a logarithm by multiplying the melanoma thickness, square of peritumoural lymphatic vessel density and the number "2" for the present lymphatic invasion. No statistically significant difference was observed between lymph node metastatic and nonmetastatic melanomas regarding the lymphatic invasion. Metastatic melanomas showed a significantly higher Shields index value than nonmetastatic melanomas (p = 0.00). Area under the receiver operator characteristic (ROC) curve (AUC) proved that the Shields index (AUC = 0.86, 95% confidence interval (CI) 0.79-0.93, p = 0.00) was the most accurate predictor of lymph node status, followed by the melanoma thickness (AUC = 0.76, 95% CI 0.67-0.86, p = 0.00) and American Joint Committee on Cancer (AJCC) staging (AUC = 0.75, 95% CI 0.66-0.85, p = 0.00), while lymphatic invasion was not successful in predicting (AUC = 0.56, 95% CI 0.45-0.67, p = 0.31). The Shields index achieved 81.3% sensitivity and 75% specificity (cut-off mean value). Our findings show that D2-40/S-100 immunohistochemical analysis of lymphatic invasion cannot be used for predicting the lymph node status, while the Shields index calculation predicts disease outcome more accurately than the melanoma thickness and AJCC staging. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights

  3. A model to measure lymphatic drainage from the eye.

    Science.gov (United States)

    Kim, Minhui; Johnston, Miles G; Gupta, Neeru; Moore, Sara; Yücel, Yeni H

    2011-11-01

    Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and recently described ciliary body lymphatics. The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. This study describes that model and presents our initial findings. Following intracameral injection of (125)I-bovine serum albumin (BSA), lymph was continuously collected via cannulated cervical lymphatic vessels and the thoracic lymphatic duct over either a 3-h or 5-h time period. In the same animals, blood samples were collected from the right jugular vein every 15 min. Lymphatic and TM drainage were quantitatively assessed by measuring (125)I-BSA in lymph and plasma, respectively. Radioactive tracer levels were also measured in UVS and "other" ocular tissue, as well as periocular tissue harvested 3 and 5 h post-injection. Tracer recovered from UVS tissue was used to estimate UVS drainage. The amount of (125)I-BSA recovered from different fluid and tissue compartments was expressed as a percentage of total recovered tracer. Three hours after tracer injection, percentage of tracer recovered in lymph and plasma was 1.64% ± 0.89% and 68.86% ± 9.27%, respectively (n = 8). The percentage of tracer in UVS, other ocular and periocular tissues was 19.87% ± 5.59%, 4.30% ± 3.31% and 5.32% ± 2.46%, respectively. At 5 h (n = 2), lymphatic drainage was increased (6.40% and 4.96% vs. 1.64%). On the other hand, the percentage of tracer recovered from UVS and other ocular tissue had decreased, and the percentage from periocular tissue showed no change. Lymphatic drainage increased steadily over the 3 h post-injection period, while TM

  4. AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation.

    Science.gov (United States)

    Boscolo, Elisa; Coma, Silvia; Luks, Valerie L; Greene, Arin K; Klagsbrun, Michael; Warman, Matthew L; Bischoff, Joyce

    2015-04-01

    Lymphatic malformations (LM) are characterized by abnormal formation of lymphatic vessels and tissue overgrowth. The lymphatic vessels present in LM lesions may become blocked and enlarged as lymphatic fluid collects, forming a mass or cyst. Lesions are typically diagnosed during childhood and are often disfiguring and life threatening. Available treatments consist of sclerotherapy, surgical removal and therapies to diminish complications. We isolated lymphatic endothelial cells (LM-LEC) from a surgically removed microcystic LM lesion. LM-LEC and normal human dermal-LEC (HD-LEC) expressed endothelial (CD31, VE-Cadherin) as well as lymphatic endothelial (Podoplanin, PROX1, LYVE1)-specific markers. Targeted gene sequencing analysis in patient-derived LM-LEC revealed the presence of two mutations in class I phosphoinositide 3-kinases (PI3K) genes. One is an inherited, premature stop codon in the PI3K regulatory subunit PIK3R3. The second is a somatic missense mutation in the PI3K catalytic subunit PIK3CA; this mutation has been found in association with overgrowth syndromes and cancer growth. LM-LEC exhibited angiogenic properties: both cellular proliferation and sprouting in collagen were significantly increased compared with HD-LEC. AKT-Thr308 was constitutively hyper-phosphorylated in LM-LEC. Treatment of LM-LEC with PI3-Kinase inhibitors Wortmannin and LY294 decreased cellular proliferation and prevented the phosphorylation of AKT-Thr308 in both HD-LEC and LM-LEC. Treatment with the mTOR inhibitor rapamycin also diminished cellular proliferation, sprouting and AKT phosphorylation, but only in LM-LEC. Our results implicate disrupted PI3K-AKT signaling in LEC isolated from a human lymphatic malformation lesion.

  5. 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.

  6. Head and neck lymphatic malformation treatment: a systematic review.

    Science.gov (United States)

    Adams, Mary Theresa; Saltzman, Babette; Perkins, Jonathan A

    2012-10-01

    To systematically review literature pertaining to head and neck lymphatic malformation treatment and to use individual-level data presented in qualifying case series to describe the reported efficacy, complications, and functional impact of surgery and sclerotherapy. The authors evaluated whether treatment modalities differ by lymphatic malformation stage. The terms lymphangioendothelioma, lymphangioma, cystic hygroma, and malformation were used to perform an Ovid literature search yielding 6292 references. The authors excluded references that did not involve head and neck lymphatic malformation treatment, include at least 5 patients, follow patients 1 year, define treatment modality, and state complications. The authors summarized data from 1205 patients reported in 41 articles. Individual-level data, in the 29 articles reporting these data, were pooled and tabulated. The absence of within-study comparisons of treatment success, as well as the range of reporting methods, precluded a formal meta-analysis. Most reports were case series (37; 90%). The primary treatment modality was sclerotherapy in 17 (41%), surgery in 16 (39%), or surgery combined with other modalities in 9 (20%). Individual-level data were captured for 283 patients. No treatment modality clearly resulted in superior treatment outcome. Complications were more frequent in surgical series but were reported inconsistently in sclerotherapy studies. There is evidence that lymphatic malformation treatment can be done effectively with surgery or sclerotherapy, but further study is necessary to determine which is superior. Standardized guidelines for reporting lymphatic malformation case series do not currently exist, making comparison of treatment outcomes of differing treatment modalities difficult.

  7. Structural and functional features of central nervous system lymphatics

    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.; Kevin, S. Lee; Harris, Tajie H.; Kipnis, Jonathan

    2015-01-01

    One of the characteristics of the CNS is the lack of a classical lymphatic drainage system. Although it is now accepted that the CNS undergoes constant immune surveillance that takes place within the meningeal compartment1–3, the mechanisms governing the entrance and exit of immune cells from the CNS remain poorly understood4–6. 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 CSF, 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 CNS. The discovery of the CNS lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and shed new light on the etiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction. PMID:26030524

  8. [Vascular tumours and malformations, classification, pathology and imaging].

    Science.gov (United States)

    Wassef, M; Vanwijck, R; Clapuyt, P; Boon, L; Magalon, G

    2006-01-01

    The understanding of vascular anomalies (vascular tumours and vascular malformations) was obscured, for a long time, by confusion and uncertainties in nosology and terminology. The International Society for the Study of Vascular Anomalies (ISSVA) recently adopted a classification scheme, clearly separating vascular tumours (hemangiomas of different types) which result from active cell proliferation, from vascular malformations, which are inborn defects in vascular morphogenesis. These two types of lesions have different clinical behaviour and require different diagnostic and therapeutic strategies. The most frequent vascular tumour is infantile hemangioma. Its clinical aspects and evolution are well-known. New data have been recently obtained concerning the phenotype of tumour cells and its histogenesis. Of the numerous new vascular tumours, which have been recently described, only the congenital hemangiomas, the vascular tumours associated with the Maffucci syndrome and the tumours that may be complicated by a profound thrombocytopenia (Kasabach and Merritt phenomenon) will be considered. Vascular malformations can be classified according to the vessel(s) types they are composed of. A classification table is presented, separating the malformations of vascular trunks from tissular malformations which are more intimately embedded in the surrounding tissues. The different syndromes associated with vascular anomalies take also place in this table. The clinical, imaging and histological aspects of the most frequent malformations (capillary, venous, lymphatic and arteriovenous) are presented. This classification intend to clarify the nosology and terminology of the complex field of vascular tumours and malformation and to offer a common language to the different physicians and specialists contributing, preferably with a interdisciplinary approach, to the diagnosis and treatment of these difficult lesions.

  9. Elimination of Lymphatic Filariasis in The Gambia

    Science.gov (United States)

    Rebollo, Maria P.; Sambou, Sana Malang; Thomas, Brent; Biritwum, Nana-Kwadwo; Jaye, Momodou C.; Kelly-Hope, Louise; Escalada, Alba Gonzalez; Molyneux, David H.; Bockarie, Moses J.

    2015-01-01

    Background The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission. Methodology/Principal Finding We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997–2013), and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT) test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6–7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts. Conclusions We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF. PMID

  10. Lymphocytopenia in children with lymphatic malformation.

    Science.gov (United States)

    Tempero, Richard M; Hannibal, Mark; Finn, Laura S; Manning, Scott C; Cunningham, Michael L; Perkins, Jonathan A

    2006-01-01

    To determine whether an immunologic abnormality exists in patients with lymphatic malformation (LM). Retrospective case series. Tertiary care pediatric hospital. Twenty-one consecutive patients (11 male and 10 female) undergoing LM treatment. Clinical data (ie, age, clinical LM stage, radiographic appearance, and histologic findings) were correlated with complete blood cell count and detailed lymphocyte differential. Complete blood cell counts and lymphocyte subsets were measured in 21 and 18 patients, respectively. The average age at the time of testing was 67 months (range, 1-231 months). The patients were categorized according to LM stage, including 4 (19%) with stage 1, 4 (19%) with stage 2, 4 (19%) with stage 3, 7 (33%) with stage 4, and 2 (10%) with stage 5 disease. Radiographic LM appearance was macrocystic in 6 patients (29%), mixed macrocystic and microcystic in 8 (38%), and microcystic in 7 (33%). Complete blood cell count data demonstrated lymphocytopenia in 6 patients (29%). The results of the lymphocyte subset tests showed concomitant T-, B-, and natural killer (NK)-cell deficiency in 6 (33%) of 18 patients. All 6 patients with T-cell lymphocytopenia had normal neutrophil and platelet counts. Spearman rank and chi(2) analyses showed that LM stage 4 or 5 and microcystic LM were significantly associated with lymphocytopenia (P = .002 and P = .008, respectively). Histologic analysis did not demonstrate increased lymphocytes in any LM specimens. We found T, B, and NK lymphocytopenia in patients with large bilateral or microcystic LM. Although the relationship between lymphocytopenia and infection was not addressed in this study, the recognition of lymphocytopenia in patients with LM may have important clinical and prognostic implications.

  11. VASCULAR SURGERY

    African Journals Online (AJOL)

    Venous thromboembolism (VTE) is a complex and serious condition encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), usually in the lower extremities.1,2. Thromboses can result from venous stasis, vascular injury or hypercoagulability, and those involving the deep veins proximal to the knee are ...

  12. Distinct alkaline phosphatase in serum of patients with lymphatic leukemia and infectious mononucleosis

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, H.; Moran, E.M.; Russell, R.M.; Rosenberg, I.H.

    1974-10-11

    A distinct alkaline phosphatase (phosphatase N) was demonstrated in the serum of patients with acute lymphatic leukemia, chronic lymphatic leukemia, and infectious mononucleosis. This enzyme closely resembles that extracted from the thymus of mice with lymphoma or lymphatic leukemia, both in its electrophoretic mobility and its substrate specificity. The phosphatase N activity was related to the clinical state of patients with lymphatic leukemia and disappeared with recovery from infectious mononucleosis.

  13. Emerging lymphatic imaging technologies for mouse and man.

    Science.gov (United States)

    Sevick-Muraca, Eva M; Kwon, Sunkuk; Rasmussen, John C

    2014-03-01

    The lymphatic circulatory system has diverse functions in lipid absorption, fluid homeostasis, and immune surveillance and responds dynamically when presented with infection, inflammation, altered hemodynamics, and cancer. Visualization of these dynamic processes in human disease and animal models of disease is key to understanding the contributory role of the lymphatic circulatory system in disease and to devising effective therapeutic strategies. Longitudinal, non-destructive, and repeated imaging is necessary to expand our understanding of disease progression and regression in basic science and clinical investigations. Herein we summarize recent advances in in vivo lymphatic imaging employing magnetic resonance, computed tomography, lymphoscintigraphy, and emerging optical techniques with respect to their contributory roles in both basic science and clinical research investigations.

  14. Lymphatic drainage from the eye: A new target for therapy.

    Science.gov (United States)

    Yucel, Yeni; Gupta, Neeru

    2015-01-01

    Lowering intraocular pressure (IOP) has been central to glaucoma care for over a century. In order to prevent sight loss from disease, there has been considerable focus on medical and surgical methods to improve fluid drainage from the eye. In spite of this, our understanding of exactly how aqueous humor leaves the eye is not complete. Recently, lymphatic vessels have been discovered in the human uvea, with studies showing lymphatic fluid outflow in several models, in addition to evidence for their pharmacological enhancement. The presence of a lymphatic outflow system points to an exciting, expanded understanding of how fluid and particulate materials such as proteins move out of the eye, and how IOP may be regulated. We coin the term "uveolymphatic pathway"-to reflect a comprehensive and compelling new target for glaucoma and an exciting opportunity for future investigations to better understand the eye in health and disease. © 2015 Elsevier B.V. All rights reserved.

  15. Supramicrosurgical lymphatic-venous anastomosis for postsurgical subcutaneous lymphocele treatment.

    Science.gov (United States)

    Gentileschi, Stefano; Servillo, Maria; Salgarello, Marzia

    2015-10-01

    Postsurgical subcutaneous lymphocele is caused by accidental lesion of a lymphatic vessel that keeps on flowing lymph under the scar. Traditional treatments include aspiration and compression, with probable recurrence, and sclerotherapy which destroys both lymphatic cyst and vessel, creating risk of lymphedema. We describe the case of a postsurgical subcutaneous lymphocele of the left leg that was treated by supramicrosurgical lympatic-venous anastomosis. A single anastomosis was performed end-to-end, between one lymphatic vessel, individuated through indocyanine green lymphography, and one subcutaneous vein, distally to the lymphocele, under sedation and local anesthesia. Postoperative course was uneventful; the lymphocele completely resolved and never recurred during the nine months followup. This technique may heal the lymphocele with no impairing of lymph drainage function. © 2015 Wiley Periodicals, Inc.

  16. Successful Treatment of Macroglossia Due to Lymphatic Malformation With Sirolimus.

    Science.gov (United States)

    Yesil, Sule; Bozkurt, Ceyhun; Tanyildiz, Hikmet Gülsah; Tekgunduz, Sibel Akpinar; Candir, Mehmet Onur; Toprak, Sule; Sahin, Gurses

    2015-10-01

    To evaluate the effectiveness and safety of sirolimus therapy in a child with macroglossia due to lymphatic malformation. Sirolimus treatment was applied to the patient with an initial dosing of 0.8 mg/m2 per dose, administered orally, twice daily at approximately 12-hour intervals. After 9 months of sirolimus therapy, there was a nearly complete resolution of lymphatic malformation. The last evaluation was performed 6 months after withdrawal of treatment, and the lesion had almost completely resolved. This article presents a novel approach to the treatment of lymphatic malformation of the tongue using sirolimus, which appears to be safe and effective for the management of complex cases. © The Author(s) 2015.

  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. In vivo lymphatic imaging of a human inflammatory breast cancer model.

    Science.gov (United States)

    Agollah, Germaine D; Wu, Grace; Sevick-Muraca, Eva M; Kwon, Sunkuk

    2014-01-01

    Inflammatory breast cancer (IBC) remains the most aggressive type of breast cancer with the greatest potential for metastasis and as a result, the highest mortality rate. IBC cells invade and metastasize through dermal lymphatic vessels; however, it is unknown how lymphatic drainage patterns change during IBC growth and metastasis. Herein, we non-invasively and longitudinally imaged lymphatics in an animal model of IBC using near-infrared fluorescence (NIRF) imaging. Mice were imaged in vivo prior to, and up to 11 weeks after subcutaneous or orthotopic inoculation of human IBC SUM149 cells, which were stably transfected with infrared fluorescence protein (iRFP) gene reporter (SUM149-iRFP), following intradermal (i.d.) injection of indocyanine green (ICG). Fluorescence images showed well-defined lymphatic vessels prior to SUM149-iRFP inoculation. However, altered lymphatic drainage patterns including rerouting of lymphatic drainage were detected in mice with SUM149-iRFP, due to lymphatic obstruction of normal lymphatic drainages caused by tumor growth. In addition, we observed tortuous lymphatic vessels and extravasation of ICG-laden lymph in mice with SUM149-iRFP. We also observed increased and dilated fluorescent lymphatic vessels in the tumor periphery, which was confirmed by ex vivo immunohistochemical staining of lymphatic vessels. Our pre-clinical studies demonstrate that non-invasive NIRF imaging can provide a method to assess changes in lymphatic drainage patterns during IBC growth and metastasis.

  19. The lymphatic drainage of the cranial part of the sheep's uterus and its possible functional significance.

    OpenAIRE

    Abdel Rahim, S E; Bland, K P

    1985-01-01

    The lymphatic drainage of the cranial part of the uterus is described. Some of the uterine lymphatic vessels are closely associated with the ovarian arterial supply. It is proposed that the uterine lymphatics form part of the local pathway for the transfer of uterine prostaglandin F2 alpha to the ovary for luteolysis.

  20. Efecto morfológico y funcional vascular de los andrógenos endógenos en un modelo experimental en conejos ateroscleróticos Vascular morphologic and functional effect of endogenous androgens in an experimental atherosclerotic rabbits' model

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2007-12-01

    Full Text Available Resumen: estudios clínicos y experimentales previos, sugieren que los andrógenos podrían tener un efecto adverso, neutral o benéfico, sobre la aterosclerosis y sus manifestaciones clínicas. Métodos: se realizó un estudio experimental aleatorizado y controlado en 40 conejos de raza Nueva Zelanda. 20 animales se sometieron a orquidectomía y 20 se alimentaron con dieta aterogénica durante 20 semanas. Se distribuyeron en cuatro grupos: 1: no castrados sometidos a dieta normal; 2: castrados sometidos a dieta normal; 3: no castrados sometidos a dieta aterogénica y 4: castrados sometidos a dieta aterogénica. Se hicieron mediciones de colesterol total y testosterona libre. Después de la eutanasia, se cuantificó en aorta la relajación arterial independiente de endotelio y dependiente de endotelio in-vitro, y se hicieron análisis histomorfométricos de la aorta torácica para cuantificar la formación de placa aterosclerótica. Resultados: los animales sometidos a dieta normal (n=20 tuvieron colesterol total de 51,1 ± 8,5 mg/dL y los sometidos a dieta aterogénica de 429,2 ± 262,0 mg/dL (p Summary: previous clinical and experimental studies suggest that androgens could have an adverse, neutral or beneficial effect on atherosclerosis and its clinical manifestations. Methods: an experimental, randomized controlled study in 40 New Zealand white male rabbits was realized. 20 rabbits underwent orchiectomy and 20 were fed with an atherogenic diet for 20 weeks. These were distributed in four groups: 1. non-castrated under normal diet, 2. castrated under normal diet, 3. non-castrated under atherogenic diet, and 4. castrated under atherogenic diet. Total cholesterol and free testosterone were measured. After euthanasia, arterial relaxation independent of endothelium was quantified in aorta, as well as the one depending on endothelium, in vitro, and histomorphometric analysis of thoracic aorta were made in order to quantify the atherosclerotic

  1. 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...... the lymphatic system in obese subjects. Furthermore, they suggest that postprandial changes in ATLD taking place in lean subjects are not observed in obese subjects. This may have a role in the development of obesity-related inflammation in hypertrophic adipose tissue.International Journal of Obesity advance...

  2. Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies.

    Science.gov (United States)

    Wassef, Michel; Blei, Francine; Adams, Denise; Alomari, Ahmad; Baselga, Eulalia; Berenstein, Alejandro; Burrows, Patricia; Frieden, Ilona J; Garzon, Maria C; Lopez-Gutierrez, Juan-Carlos; Lord, David J E; Mitchel, Sally; Powell, Julie; Prendiville, Julie; Vikkula, Miikka

    2015-07-01

    Vascular anomalies represent a spectrum of disorders from a simple "birthmark" to life- threatening entities. Incorrect nomenclature and misdiagnoses are commonly experienced by patients with these anomalies. Accurate diagnosis is crucial for appropriate evaluation and management, often requiring multidisciplinary specialists. Classification schemes provide a consistent terminology and serve as a guide for pathologists, clinicians, and researchers. One of the goals of the International Society for the Study of Vascular Anomalies (ISSVA) is to achieve a uniform classification. The last classification (1997) stratified vascular lesions into vascular malformations and proliferative vascular lesions (tumors). However, additional disease entities have since been identified that are complex and less easily classified by generic headings, such as capillary malformation, venous malformation, lymphatic malformation, etc. We hereby present the updated official ISSVA classification of vascular anomalies. The general biological scheme of the classification is retained. The section on tumors has been expanded and lists the main recognized vascular tumors, classified as benign, locally aggressive or borderline, and malignant. A list of well-defined diseases is included under each generic heading in the "Simple Vascular Malformations" section. A short definition is added for eponyms. Two new sections were created: one dealing with the malformations of individually named vessels (previously referred to as "truncular" malformations); the second groups lesions of uncertain or debated nature (tumor versus malformation). The known genetic defects underlying vascular anomalies are included in an appendix. This classification is meant to be a framework, acknowledging that it will require modification as new scientific information becomes available. Copyright © 2015 by the American Academy of Pediatrics.

  3. Lymphotoxins Promote the Progression of Human Lymphatic Malformation by Enhancing Lymphatic Endothelial Cell Proliferation.

    Science.gov (United States)

    Yang, Jie-Gang; Sun, Yan-Fang; He, Ke-Fei; Ren, Jian-Gang; Liu, Zhuo-Jue; Liu, Bing; Zhang, Wei; Zhao, Yi-Fang

    2017-08-31

    Formation of inflammation-related tertiary lymphoid organs promotes human lymphatic malformation (LM) development. However, the role of lymphotoxins (LTs) and LT-related inducible ligand, the crucial mediators for tertiary lymphoid organ formation, is undetermined in LMs. Herein, we show that LTs and LT-related inducible ligand promote LM development by enhancing lymphatic endothelial cell (LEC) proliferation via activating NF-κB pathways. The expression of LTs and their receptors was increased in LMs, especially the infected ones, when compared with normal skins. Nuclear translocation of p65, p52, and RelB in the LECs of LMs indicated the activation of classic and alternative NF-κB pathways. Pearson's correlation and cluster analysis suggested the close relationship between LEC proliferation and NF-κB activation. Moreover, in vitro data demonstrated LTs accelerated the proliferation of human dermal LECs (HdLECs) through activation of NF-κB. In addition, lipopolysaccharide (LPS) up-regulated LT receptor expression in HdLECs, leading to increased sensitivity to LTs. Suppression of LT receptors hampered LPS-enhanced HdLEC proliferation, indicating the crucial role of LT pathways in inflammatory lymphangiogenesis. Besides, evidence from the LM rat models demonstrated LTα and LPS enhanced LEC proliferation, therefore promoting LM development. Blocking LT pathways by neutralizing antibodies against LTα and LTβR may decelerate the growth of the disease. In summary, our present study demonstrated activation of LT signaling pathways in LECs contributed to the progression of LMs. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

  6. 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.

  7. [Clinicopathologic study of pediatric vascular anomalies: a report of 117 cases].

    Science.gov (United States)

    Niu, H L; Zhou, S Y; Lin, Q Q; Yi, P; Wang, F H; Gao, Q; Chen, Z R; Xia, J Q; Zheng, H C; Zeng, R X

    2016-04-08

    To study the clinicopathologic features of pediatric vascular anomalies and application of ISSVA classification. The clinical features, histopathologic findings and immunohistochemical results were analyzed in 117 cases of pediatric vascular anomalies encountered during the period from May 2014 to May 2015. A total of 117 cases of vascular anomalies were studied. The age of patients ranged from 18 hours after birth to 11 years (mean age =34 months and median age =27 months). There were 73 male patients and 44 female patients, with the male-to-female ratio being 1.7∶1.0. Congenital skin lesions were found in 37 cases (31.6%). The common sites of involvement included head and neck region (46 cases, 39.3%), trunk (28 cases, 23.9%), extremities (14 cases, 12.0%) and internal viscera (31 cases, 26.5%). According to the new ISSVA classification, there were 74 cases of vascular malformations and 43 cases of vascular neoplasms (ratio=1.7∶1.0). The commonest vascular tumor encountered was infantile hemangioma (21 cases, 48.8%), including 17 cases in proliferative phase and 4 cases in involutive phase. Thirteen cases (23.3%) of congenital hemangioma were found, with 8 cases of rapidly involuting congenital hemangioma and 5 cases of non-involutive congenital hemangioma. Three of the congenital hemangioma occurred in liver. There were 5 cases (11.6%) of pyogenic granuloma, 3 cases (7.0%) of tufted angioma and 1 case (2.3%) of Kaposiform hemangioendothelioma. Amongst the 74 cases of vascular malformations encountered, lymphatic malformation was found in 47 cases (63.5%), venous malformation in 15 cases (20.2%), lymphatic-venous malformation in 11 cases (14.9%) and arteriovenous malformation in 1 case (1.4%). All cases of vascular anomalies were all positive for CD31 on immunostaining. Glut1 and CD15 were positive both in proliferative and involutive phases of the 21 cases of infantile hemangioma, while other vascular tumors and vascular malformations were negative. Forty

  8. Scintigraphic localization of lymphatic leakage site after oral administration of iodine-123-IPPA.

    Science.gov (United States)

    Kettner, B I; Aurisch, R; Rückert, J C; Sandrock, D; Munz, D L

    1998-12-01

    Chylothorax can occur secondary to traumatic lesions of the thoracic duct caused by chest injuries, surgical procedures involving the pleural space, neoplasms or malformations of the lymphatics. Lymphatic leakage sites were localized by scintigraphy after oral administration of the 123I-labeled long-chain fatty acid derivative iodophenyl pentadecanoic acid (IPPA). We report on three patients with different lymphatic leakage sites and on one normal control subject. IPPA scintigraphy localized the lymphatic leakage site correctly in all three patients. In two of them, the method even guided the successful surgical treatment of the leakage. This approach is suitable for detecting lymphatic leakages of intestinal origin.

  9. Lymphatic vessel density and VEGF-C expression as independent predictors of melanoma metastases.

    Science.gov (United States)

    Špirić, Zorica; Eri, Živka; Erić, Mirela

    2017-11-01

    In many patients, the clinical behaviour of cutaneous melanoma is very difficult to predict by traditional histologic and clinical parameters. This study aimed to examine the role of quantitative parameters of tumour lymphangiogenesis and vascular endothelial growth factor (VEGF)-C in predicting metastatic risk in patients with cutaneous melanoma. One hundred melanoma specimens were stained with lymphatic-specific antibody D2-40 and with anti-VEGF-C antibody. Quantitative parameters of lymphangiogenesis-lymphatic vessel density (LVD) and lymphatic vessel area (LVA)-were determined by computer-assisted morphometric analysis. Moderate or strong staining was assessed as a positive expression of VEGF-C in tumour cells. Univariate analysis revealed that intratumoural LVD, peritumoural LVD, VEGF-C expression in tumour cells, melanoma thickness, Clark level, ulceration, gender and histologic type were significant predictors of lymph node metastasis (p = 0.000, p = 0.000, p = 0.000, p = 0.000, p = 0.005, p = 0.005, p = 0.011 and p = 0.027, respectively). No significant association of intratumoural and peritumoural LVA with metastases was found. In multivariate analysis, independent predictors of metastatic risks were melanoma thickness [odds ratio OR = 1.655, 95% confidence interval (CI) 1.102-2.484, p = 0.015], intratumoural LVD (OR = 1.086, 95% CI 1.027-1.148, p = 0.004), peritumoural LVD (OR = 1.050, 95% CI 1.008-1.094, p = 0.020) and a positive VEGF-C expression in tumour cells (OR = 20.337, 95% CI 2.579-160.350, p = 0.004). This study identified intratumoural and peritumoural LVD and the VEGF-C expression in tumour cells as more significant predictors of metastatic risk than melanoma thickness, ulceration and other clinical-pathological parameters. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Prevalence of Lymphatic Filariasis among Adults in Ofumbongha ...

    African Journals Online (AJOL)

    This work assesses the prevalence of lymphatic filariasis in the rural Ofumbongha communities (IIV), in Obubra Local Government Area of Cross River State, Nigeria. The study population consisted of both sexes 16 years of age and above. Blood sampling was from the thumb. Giemsa Staining Technique was employed in ...

  11. Utility of a microwave surgical instrument in sealing lymphatic vessels.

    Science.gov (United States)

    Takebayashi, Katsushi; Shiomi, Hisanori; Naka, Shigeyuki; Murayama, Hiroyuki; Murakami, Koichiro; Akabori, Hiroya; Yamaguchi, Tsuyoshi; Shimizu, Tomoharu; Murata, Satoshi; Yamamoto, Hiroshi; Kurumi, Yoshimasa; Tani, Tohru

    2013-08-01

    This study assessed the ability of a novel microwave coagulation surgical instrument (MWCX) to seal lymphatic vessels when compared with LigaSure (Valleylab, Boulder, CO), the Harmonic Scalpel (HS; Ethicon Endo-Surgery, Cincinnati, OH), and electric cautery. The burst pressure of pig inguinal lymphatic vessels was assessed after the sealing of vessels with each surgical instrument. The rate of lymphorrhea from pig mesenteric lymphatic vessels was also investigated using indocyanine green and visualized with the Photodynamic Eye system (Hamamatsu Hotoniks, Hamamatsu, Japan). Burst pressures were higher with MWCX (average, 300 mm Hg), LigaSure (average, 290 mm Hg), and HS (average, 253 mm Hg) when compared with electric cautery (average, 152.3 mm Hg; vs MWCX: P = .002, vs LigaSure: P = .002, vs HS: P = .004). The rate of lymphorrhea was significantly lower with LigaSure (13.3%), HS (18.8%), and MWCX (13.3%) when compared with electric cautery (77.3%; vs LigaSure: P lymphatic vessels. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. A comparative study of chronic lymphatic filariasis-related ...

    African Journals Online (AJOL)

    The paucity of socio-cultural data and a lack of understanding and documentation of lymphatic filariasis. socio-economic consequences have led to a gross underestimation of its impact in Nigeria. However, to increase the success of elimination strategies, the socio-cultural understandings of affected community groups are ...

  13. Study of chronic lymphatic filariasis Related Knowledge, Attitudes ...

    African Journals Online (AJOL)

    The paucity of socio-cultural data and a lack of understanding and documentation of Lymphatic filariasis' socio-economic consequences have led to gross underestimation of its impact in Nigeria. However, to increase the success of elimination strategies, the socio-cultural understandings of affected community groups are ...

  14. Perception, practices and health-seeking behaviour of lymphatic ...

    African Journals Online (AJOL)

    Quantitative and qualitative studies to investigate lymphatic-filariasis-related perceptions, practices and health-seeking behaviour of patients was conducted in Benue State, Nigeria. Questionnaires, key informant, interviews and Matrix Ranking Exercises were employed to collect data. A total of 113 questionnaires ...

  15. Transmural pressure during cardiogenic oscillations in rodent diaphragmatic lymphatic vessels.

    Science.gov (United States)

    Negrini, Daniela; Moriondo, Andrea; Mukenge, Sylvain

    2004-01-01

    The mechanism of initial lymphatic filling and the role of cardiogenic tissue motion in promoting lymph formation and propulsion are at present still controversial issues, in particular when considering interstitial tissues whose fluid pressure is well below atmospheric. To elucidate these aspects, the micropuncture technique was used to record interstitial (P(int)) and intralymphatic pressure (P(lymph)) simultaneously in the diaphragmatic lymphatic plexus draining the pleural cavity. The diaphragmatic lymphatic network was identified in anesthetized rabbits and rats through fluorescent dextrans injected intrapleurally. All P(lymph) and P(int) traces were pulsatile, oscillating either in-phase (33% of traces) or out-of-phase (67%) during cardiogenic swings. P(lymph) swept between -4.1 +/- 0.9 (SE) mmHg and 3.5 +/- 1.1 mmHg in rabbits, and between -5.1 +/- 1.0 mmHg and -2.7 +/- 1.1 mmHg in rats. P(int) oscillated between -0.8 +/- 0.7 mmHg and 4.9 +/- 0.7 mmHg in rabbits, and between -0.6 +/- 0.8 mmHg and 0.9 +/- 0.7 mmHg in rats. The data revealed a great functional complexity of the diaphragmatic lymphatic network and suggested that cardiogenic oscillations may play an important role in promoting lymph formation and propulsion from interstitial tissues with subatmospheric tissue pressure.

  16. Research Note: Lymphatic filariasis (LF) Aedes albopictus : A new ...

    African Journals Online (AJOL)

    Lymphatic filariasis, an ancient disease is a major global problem infecting more than 120 million men, women and children. Vectors for the causative ... This is no good news considering the health implications and bearing in mind that Aedes albopictus is a competent vector for at least 22 arboviruses. The finding of W.

  17. Integrated morbidity management for lymphatic filariasis and podoconiosis, Ethiopia.

    Science.gov (United States)

    Deribe, Kebede; Kebede, Biruck; Tamiru, Mossie; Mengistu, Belete; Kebede, Fikreab; Martindale, Sarah; Sime, Heven; Mulugeta, Abate; Kebede, Biruk; Sileshi, Mesfin; Mengiste, Asrat; McPherson, Scott; Fentaye, Amha

    2017-09-01

    Lymphatic filariasis and podoconiosis are the major causes of tropical lymphoedema in Ethiopia. The diseases require a similar provision of care, but until recently the Ethiopian health system did not integrate the morbidity management. To establish health-care services for integrated lymphoedema morbidity management, the health ministry and partners used existing governmental structures. Integrated disease mapping was done in 659 out of the 817 districts, to identify endemic districts. To inform resource allocation, trained health extension workers carried out integrated disease burden assessments in 56 districts with a high clinical burden. To