Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells via Neuropilin-2/PlexinD1.

Science.gov (United States)

Liu, Xinyi; Uemura, Akiyoshi; Fukushima, Yoko; Yoshida, Yutaka; Hirashima, Masanori

2016-11-22

The vertebrate circulatory system is composed of closely related blood and lymphatic vessels. It has been shown that lymphatic vascular patterning is regulated by blood vessels during development, but its molecular mechanisms have not been fully elucidated. Here, we show that the artery-derived ligand semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced lymphatic vascular branching. Conditional ablation in mice demonstrates that PlexinD1 is primarily required in lymphatic endothelial cells (LECs). In vitro analyses show that Sema3G binds to neuropilin-2 (Nrp2), which forms a receptor complex with PlexinD1. Sema3G induces cell collapse in an Nrp2/PlexinD1-dependent manner. Our findings shed light on a molecular mechanism by which LECs are distributed away from arteries and form a branching network during lymphatic vascular development. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Exercise training improves obesity-related lymphatic dysfunction.

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

2016-08-01

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

[Pleural lymphatics and effusions].

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Mordant, P; Arame, A; Legras, A; Le Pimpec Barthes, F; Riquet, M

2013-06-01

The pleural lymphatic system has a great absorption capacity. Its most known function is fluid resorption. The pleura which cover the lungs (visceral pleura), the mediastinum, diaphragm and thoracic wall (parietal pleura) are formed by a mesothelial cell layer (mesothelium). This permeable layer is in direct contact with the vascular endothelium. The mesothelium is based over a connective tissue (interstitium) containing the blood and lymphatic vessels. The primary lymphatic vessels drain interstitium but are also in direct contact with pleural space by the stoma or openings, situated in the lower parts of parietal pleura, i.e: diaphragm, over lower ribs and mediastinum but not existing in the adjacent visceral pleura. In addition, a part of interstitial pulmonary fluid entered in the pleural cavity by passing the visceral pleura would be absorbed by these openings. The resorption process is active and directly related to the function of smooth muscles of lymphatic vessels. Besides resorption, we must emphasize that this "pumping" activity is permanent and the origin of negative pressure (the pleural void) in pleural cavity, a unique property. The other resorbed elements are molecules, bacterial and cellular debris, cells, red blood and cancer cells. Copyright © 2013. Published by Elsevier Masson SAS.

Lymphatic involvement in the histopathogenesis of mucous retention cyst.

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Kundu, Sukalyan; Cheng, Jun; Maruyama, Satoshi; Suzuki, Makoto; Kawashima, Hiroyuki; Saku, Takashi

2007-01-01

Mucous retention cyst results from extravasation of saliva. Our intent was to study the role of lymphatics in its pathogenesis. Twenty-three surgical specimens of mucous retention cyst of the lip were examined for involvement of lymphatic vessels by a comparative immunohistochemical demonstration of lymphatic and blood vascular endothelial cells, as well as lymphatic and salivary contents. Mucous retention cysts were histopathologically classified into three stages: early, intermediate, and advanced. In the early stage, there was diffuse extravasation of mucous material in the interstitium of the lamina propria or the submucosal layer of the oral mucosa. In the intermediate stage, lymphatics, which were clearly revealed and immunohistochemically distinguished from blood vessels by monoclonal antibody D2-40, were dilated and finally ruptured, leaving fragments of lymphatic walls in the periphery of mucous pools. In the advanced stage, thick cyst walls of granulation tissue were formed around mucous retention. Lymphatics were no longer involved in the granulation tissue wall, which was actively driven by blood vessel formation. The results suggest that the lymphatic rupture seems to contribute to the enlargement in the pathogenesis of mucous retention cyst.

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.

Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

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Souheil El-Chemaly

2012-09-01

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

Photoacoustic imaging of lymphatic pumping

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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.

Lymphatic endothelial cell line (CH3) from a recurrent retroperitoneal lymphangioma.

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Way, D; Hendrix, M; Witte, M; Witte, C; Nagle, R; Davis, J

1987-09-01

An endothelial cell line derived from a massive recurrent chyle-containing retroperitoneal lymphangioma was isolated in monolayer culture. Scanning and transmission electron microscopy and immunohistochemistry confirmed a close resemblance to blood vascular endothelium with typical cobblestone morphology, positive immunofluorescence staining for endothelial marker Factor VIII-associated antigen and fibronectin, and prominent Weibel-Palade bodies. The endothelial cells also exhibited other ultrastructural features characteristic of lymphatic endothelium, including sparse microvillous surface projections, overlapping intercellular junctions, and abundant intermediate filaments. This endothelial cell line represents a new source of proliferating lymphatic endothelium for future study, including structural and functional comparison to blood vascular endothelium.

Immunohistochemical Examination on the Distribution of Cells Expressed Lymphatic Endothelial Marker Podoplanin and LYVE-1 in the Mouse Tongue Tissue

Science.gov (United States)

Noda, Yuya; Amano, Ikuko; Hata, Minoru; Kojima, Hiroshi; Sawa, Yoshihiko

2010-01-01

The clinical study for lingual disease requires the detailed investigation of the lingual lymphatic network and lymphatic marker-positive cells. Recently, it has been reported that several tissue cells and leukocytes express lymphatic markers, LYVE-1 and podoplanin. This study was aimed to clarify the lingual distribution of cells expressing LYVE-1 and podoplanin. In the mouse tongue, podoplanin is expressed in nerve sheaths, lingual gland myoepithelial cells, and lymphatic vessels. LYVE-1 is expressed in the macrophage marker Mac-1-positive cells as well as lymphatic vessels, while factor-VIII was detected in only blood endothelial cells. α-SMA was detected in vascular smooth muscle and myoepithelial cells. Therefore, identification of lymphatic vessels in lingual glands, the combination of LYVE-1 and factor-VIII, or LYVE-1 and Mac-1 is useful because myoepithelial cells express podoplanin and α-SMA. The immunostaining of factor-VIII on lymphatic vessels was masked by the immunostaining to LYVE-1 or podoplanin because lymphatic vessels express factor-VIII to a far lesser extent than blood vessels. Therefore, except for the salivary glands, the combination of podoplanin and α-SMA, or factor-VIII is useful to identify lymphatic vessels and blood vessels with smooth muscle, or blood capillaries. PMID:20514293

Imaging evaluation of fetal vascular anomalies

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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.)

Imaging evaluation of fetal vascular anomalies

International Nuclear Information System (INIS)

Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal; Adams, Denise M.; Gupta, Anita; Lim, Foong-Yen

2015-01-01

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.)

The deep lymphatic anatomy of the hand.

Science.gov (United States)

Ma, Chuan-Xiang; Pan, Wei-Ren; Liu, Zhi-An; Zeng, Fan-Qiang; Qiu, Zhi-Qiang

2018-04-03

The deep lymphatic anatomy of the hand still remains the least described in medical literature. Eight hands were harvested from four nonembalmed human cadavers amputated above the wrist. A small amount of 6% hydrogen peroxide was employed to detect the lymphatic vessels around the superficial and deep palmar vascular arches, in webs from the index to little fingers, the thenar and hypothenar areas. A 30-gauge needle was inserted into the vessels and injected with a barium sulphate compound. Each specimen was dissected, photographed and radiographed to demonstrate deep lymphatic distribution of the hand. Five groups of deep collecting lymph vessels were found in the hand: superficial palmar arch lymph vessel (SPALV); deep palmar arch lymph vessel (DPALV); thenar lymph vessel (TLV); hypothenar lymph vessel (HTLV); deep finger web lymph vessel (DFWLV). Each group of vessels drained in different directions first, then all turned and ran towards the wrist in different layers. The deep lymphatic drainage of the hand has been presented. The results will provide an anatomical basis for clinical management, educational reference and scientific research. Copyright © 2018 Elsevier GmbH. All rights reserved.

Brain drains: new insights into brain clearance pathways from lymphatic biology.

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Bower, Neil I; Hogan, Benjamin M

2018-05-01

The lymphatic vasculature act as the drainage system for most of our tissues and organs, clearing interstitial fluid and waste and returning them to the blood circulation. This is not the case for the central nervous system (CNS), which is devoid of parenchymal lymphatic vessels. Nevertheless, the brain is responsible for 25% of the body's metabolism and only compromises 2% of the body's mass. This high metabolic load requires an efficient system to remove waste products and maintain homeostasis. Well-described mechanisms of waste clearance include phagocytic immune cell functions as well as perivascular fluid flow; however, the need for active drainage of waste from the brain is becoming increasingly appreciated. Recent developments in lymphatic vascular biology challenge the proposition that the brain lacks lymphatic drainage or an equivalent. In this review, we describe the roles of the glymphatic system (a key drainage mechanism in the absence of lymphatics), the recently characterized meningeal lymphatic vessels, and explore an enigmatic cell population found in zebrafish called mural lymphatic endothelial cells. These systems may play important individual and collective roles in draining and clearing wastes from the brain.

Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion.

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Pavlov, Vadim; Rosental, Benyamin; Hansen, Nathaniel F; Beers, Jody M; Parish, George; Rowbotham, Ian; Block, Barbara A

2017-07-21

The lymphatic system in teleost fish has genetic and developmental origins similar to those of the mammalian lymphatic system, which is involved in immune response and fluid homeostasis. Here, we show that the lymphatic system of tunas functions in swimming hydrodynamics. Specifically, a musculo-vascular complex, consisting of fin muscles, bones, and lymphatic vessels, is involved in the hydraulic control of median fins. This specialization of the lymphatic system is associated with fish in the family Scombridae and may have evolved in response to the demand for swimming and maneuvering control in these high-performance species. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

FGF-dependent metabolic control of vascular development

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Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

2017-01-01

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

The prognostic significance of lymphatics in colorectal liver metastases.

Science.gov (United States)

Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

2014-01-01

Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

The Prognostic Significance of Lymphatics in Colorectal Liver Metastases

Directory of Open Access Journals (Sweden)

Vijayaragavan Muralidharan

2014-01-01

Full Text Available Background. Colorectal Cancer (CRC is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%–60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM and surrounding host tissue. Lymphatic vessel density (LVD was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P=0.01, P>0.01, and P=0.05, resp.. Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P=0.05. Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

Lymphatic vessels assessment in feline mammary tumours

International Nuclear Information System (INIS)

Sarli, Giuseppe; Sassi, Francesco; Brunetti, Barbara; Rizzo, Antonio; Diracca, Laura; Benazzi, Cinzia

2007-01-01

The lymphatic vessels play a crucial role in a variety of human cancers since tumour cell lymphatic invasion significantly influences prognosis. It is not known if pre-existing lymphatics are enough for tumour dissemination or de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both lymphatic and blood vessels during embryonic development, and only for lymphatics after birth. VEGF is a mediator of both vasculogenesis and angiogenesis, regulates the growth of lymphatics in various experimental models, and is produced in many solid tumours. CD44 mediates hyaluronic acid (HA)-dependent cell adhesion: besides promoting invasion, this interaction also supports neoangiogenesis that indirectly stimulates tumour cell proliferation. The expression of VEGF-C (Vascular Endothelial Growth Factor – C), its receptor VEGFR-3 and CD44, were studied on feline mammary samples to assess the importance of lymphangiogenesis and lymphangiotrophism in neoplasia. Samples were taken from six normal mammary glands (NMG), ten benign (BT) and 32 malignant (MT) tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains were applied to 4 μm-thick sections, and their expression evaluated in intratumoral/extratumoral and intramammary/extramammary fields. All groups revealed a higher number of lymphatics in the extratumoral/extramammary areas. VEGF-C expression in the epithelium paralleled the number of positive vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral than intratumoral fields in tumours and showed a significant increase in extramammary/extratumoral fields from NMG to MT. Pearson test showed a significant and inversely proportional correlation between CD44 expression and the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours. The number of both VEGFR-3 positive and negative lymphatics in the extratumoral

Cholinergic innervation of human mesenteric lymphatic vessels.

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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.

Overview of vascular disease

International Nuclear Information System (INIS)

Bisset, G.S. III

1998-01-01

Vascular disease in the pediatric population is a poorly understood process which is often underestimated in its incidence. The common beginnings of such ubiquitous diseases as atherosclerosis manifest themselves at a cellular level shortly after birth. Other common systemic disorders, including congestive heart failure and sepsis, are also intricately associated with dysfunctional vasculature. Progress in the understanding of normal and pathophysiologic processes within the vascular system begins with the 'control center' - the endothelial cell. The purpose of this review is to consolidate a body of knowledge on the processes that occur at the cellular level within the blood vessel wall, and to simplify the understanding of how imbalances in these physiologic parameters result in vascular disease. (orig.)

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...

Endothelial ERK signaling controls lymphatic fate specification

Science.gov (United States)

Deng, Yong; Atri, Deepak; Eichmann, Anne; Simons, Michael

2013-01-01

Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1S259A) that is associated with Noonan syndrome. Expression of mutant RAF1S259A in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar “RASopathies.” Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1S259A. These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related diseases. PMID:23391722

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

2017-12-04

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.

Low lymphatic vessel density associates with chronic rhinosinusitis with nasal polyps.

Science.gov (United States)

Luukkainen, A; Seppälä, M; Renkonen, J; Renkonen, R; Hagstrő M, J; Huhtala, H; Rautiainen, M; Myller, J; Paavonen, T; Ranta, A; Torkkeli, T; Toppila-Salmi, S

2017-06-01

Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation phenotypes with different pathomechanisms. In order to understand the development of tissue edema, the present study aimed to evaluate lymphatic vessel density in CRSsNP, CRSwNP and ACP. 120 retrospective nasal and maxillary sinus specimens were stained immunohistochemically with a von Willebrand factor polyclonal antibody recognizing vascular and lymphatic endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic endothelium. Vessels were studied by microscopy in a blinded fashion, and the vessel density and the relative density of lymphatic vessels were calculated. Patient characteristic factors and follow-up data of in average 9 years were collected from patient records. In the nasal cavity, the low absolute and relative density of vessels and of lymphatic vessels was associated with CRSwNP and ACP tissues compared to control inferior turbinate. This was observed also in the inflammatory hotspot area. In the maxillary sinus, lower absolute and relative density of lymphatic vessels associated with the CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with the need for revision CRS-surgery. As a conclusion, low density of lymphatic vessels distinguished patients with CRSwNP not only in the hotspot area of polyp tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density seems to associate with polyp recurrence. Further studies are still needed to explore if formation of nasal polyps could be diminished by intranasal therapeutics affecting lymphangiogenesis.

Characterization of vascular lesions in pigs affected by porcine circovirus type 2-systemic disease.

Science.gov (United States)

Resendes, A R; Segalés, J

2015-05-01

Vascular lesions and their association with porcine circovirus type 2 (PCV2) were evaluated in multiple organs from 10 pigs affected with PCV2-systemic disease (PCV2-SD). Animals had vascular lesions in multiple organs, consisting of lymphohistiocytic lymphangitis and/or phlebitis, mild to severe necrotizing arteritis, and thrombosis within splenic arterioles and choroid plexus capillaries. Variable amounts of PCV2 nucleic acid detected by in situ hybridization were present within endothelial cells, tunica media myocytes, and perivascular and/or intralesional inflammatory cell infiltrates. PCV2 nucleic acid was detected within endothelial cells of both lymphatic and blood vessels without lesions in the associated tissues. Necrotizing arteritis was principally present in lymph nodes and kidney and consisted of degeneration, necrosis, and pyknosis of myocytes, often with intracytoplasmic, brightly eosinophilic inclusion bodies that were strongly positive for PCV2 nucleic acid. Segmental or circumferential fibrinoid necrosis was mainly present in vessels of the lymph node, spleen, and choroid plexus and was variably associated with PCV2 nucleic acid. Severe lymphangitis associated with strong intralesional PCV2 labeling was frequently detected within the mesenteric and mediastinal lymph nodes and the lamina propria of the ileum. In most tissues, medium and large lymphatics and/or veins often had disruption of the intima and mild mononuclear inflammatory cell infiltration that was variably associated with PCV2 nucleic acid. The present study indicates that vasculitis is a frequent finding in natural cases of PCV2-SD and that PCV2 may have a direct cytopathic effect on tunica media myocytes of small- and medium-sized arteries as well as endothelium. © The Author(s) 2014.

The interaction between the meningeal lymphatics and blood-brain barrier

Science.gov (United States)

Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Dubrovsky, A.; Pavlov, A.; Shushunova, N.; Maslyakova, G.; Navolokin, N.; Bucharskaya, A.; Tuchin, V.; Kurths, J.

2018-02-01

Here we show the interaction between the meningeal lymphatic system and the blood-brain barrier (BBB) function. In normal state, the meningeal lymphatic vessels are invisible on optical coherent tomography (OCT), while during the opening of the BBB, meningeal lymphatic vessels are clearly visualized by OCT in the area of cerebral venous sinuses. These results give a significant impulse in the new application of OCT for the study of physiology of meningeal lymphatic system as well as sheds light on novel strategies in the prognosis of the opening of the BBB related with many central nervous system diseases, such as stroke, brain trauma, Alzheimers disease, etc.

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

Science.gov (United States)

Escobedo, Noelia; Oliver, Guillermo

2017-10-03

Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer

International Nuclear Information System (INIS)

Wu, Qiu-Wan; She, Hong-Qiang; Liang, Jing; Huang, Yu-Fan; Yang, Qing-Mo; Yang, Qiao-Lu; Zhang, Zhi-Ming

2012-01-01

Extracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease. ECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested. The rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05). Both ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the

Genetic Regulation of Vascular Development: Building the Zebrafish Vascular Tree

NARCIS (Netherlands)

R.L.J.M. Herpers (Robert)

2010-01-01

textabstractThe extensive networks of blood and lymphatic vessels within the vertebrate body are essential for the transport and delivery of fluids, gases, macromolecules and cells, and play important roles in facilitating immune responses. The development of the vascular tree requires a highly

Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation

Science.gov (United States)

Davis, Reema B.; Kechele, Daniel O.; Blakeney, Elizabeth S.; Pawlak, John B.

2017-01-01

Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor–like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy. Upon indomethacin challenge, Calcrlfl/fl/Prox1-CreERT2 mice demonstrated persistent inflammation and failure to recover and thrive. The epithelium and crypts of Calcrlfl/fl/Prox1-CreERT2 mice exhibited exacerbated hallmarks of disease progression, and the lacteals demonstrated an inability to absorb lipids. Furthermore, we identified Calcrl/adrenomedullin signaling as an essential upstream regulator of the Notch pathway, previously shown to be critical for intestinal lacteal maintenance and junctional integrity. In conclusion, lymphatic insufficiency and lymphangiectasia caused by loss of lymphatic Calcrl exacerbates intestinal recovery following mucosal injury and underscores the importance of lymphatic function in promoting recovery from intestinal inflammation. PMID:28352669

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.

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.

National Characteristics of Lymphatic Malformations in Children: Inpatient Estimates and Trends in the United States, 2000 to 2009.

Science.gov (United States)

Cheng, Jeffrey; Liu, Beiyu; Farjat, Alfredo E; Routh, Jonathan

2018-04-01

With ever increasing demands to manage finite resources for health care utilization, we performed an investigation to identify inpatient clinical characteristics and trends in children with lymphatic malformations using the Kids' Inpatient Database, years 2000 to 2009, to help identify populations best suited for resource deployment. Subjects included children 18 years and below with International Classification of Diseases (ICD), ninth revision code: 228.1-lymphangioma, any site. In the United States, between 2000 and 2009, inpatient pediatric patients with lymphatic malformations most commonly affected children aged 3 years and younger, urban hospital locations, and the South and West regions. There was no significant change in age of children with lymphatic malformations or the distribution of their age from year to year, P=0.948 and 0.4223, respectively. No significant evidence for seasonal variation or effect on inpatient admission was identified, P=0.7071. A great majority of admissions (>96%) were in urban locations across each year. There was also no significant change in breakdown of admissions by geographic location, P=0.7133. Further investigation may help to elucidate how to improve access to multidisciplinary vascular anomalies teams to optimize care for these children with unique and complex lymphatic malformations.

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.

Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis

Directory of Open Access Journals (Sweden)

Francesca Luisi

2016-06-01

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

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.

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.

Lymphatic Filariasis: Transmission, Treatment and Elimination

NARCIS (Netherlands)

W.A. Stolk (Wilma)

2005-01-01

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

Lymphatic imaging: Lymphography, computed tomography and scintigraphy, 2nd ed

International Nuclear Information System (INIS)

Close, M.E.; Wallace, S.

1985-01-01

The latest addition to the Golden's Diagnostic Radiology series deals not only with imaging of the lymphatic system but also with lymphatic anatomy, its pathophysiology, and treatment of disorders. The first two chapters deal with the history of the discovery of the lymphatic system and its normal anatomy. The section on technique contains practical information and discussion of lymphatic physiology and the pathology of lymphomas. Half of the book's 16 chapters are devoted to problems encountered in clinical imaging. The approach is both by anatomy (thorax, neck, abdomen) and pathology (benign disease, lymphoma, solid tumors)

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,

Anatomy of the transverse colon revisited with respect to complete mesocolic excision and possible pathways of aberrant lymphatic tumor spread.

Science.gov (United States)

Stelzner, Sigmar; Hohenberger, Werner; Weber, Klaus; West, Nicholas P; Witzigmann, Helmut; Wedel, Thilo

2016-02-01

Although lymph node metastases to pancreatic and gastroepiploic lymph node stations in transverse colon cancer have been described, the mode of lymphatic spread in this area remains unclear. This study was undertaken to describe possible pathways of aberrant lymphatic spread in the complex anatomic area of the proximal superior mesenteric artery and vein, the greater omentum, and the lower pancreatic border. Abdominal specimens obtained from four cadaveric donors were dissected according to the principles of complete mesocolic excision. The vascular architecture of the transverse colon was scrutinized in search of possible pathways of lymphatic spread to the pancreatic and gastroepiploic lymph nodes. Vascular connections between the transverse colon and the greater omentum at the level of both the hepatic and the splenic flexures could be identified. In addition, small vessels running from the transverse mesocolon to the lower pancreatic border in the area between the middle colic artery and the inferior mesenteric vein were demonstrated. Moreover, venous tributaries to the gastrocolic trunk could be exposed to highlight its surgical importance as a guiding structure for complete mesocolic excision. The technical feasibility to clearly separate embryologic compartments by predefined tissue planes in complete mesocolic excision was confirmed. However, the vicinity of all three endodermal intestinal segments (foregut, midgut, and hindgut) obviously gives way to vascular connections that might serve as potential pathways for lymphatic metastatic spread of transverse colon cancer.

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

Science.gov (United States)

Parsons-Wingerter, Patricia

2010-01-01

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

PET/CT and vascular disease: Current concepts

Energy Technology Data Exchange (ETDEWEB)

Cavalcanti Filho, Jose Leite Gondim; Souza Leao Lima, Ronaldo de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Souza Machado Neto, Luiz de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Kayat Bittencourt, Leonardo, E-mail: lkayat@terra.com.br [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Cortes Domingues, Romeu [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Fonseca, Lea Mirian Barbosa da [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil)

2011-10-15

Since its introduction in 2001, positron emission tomography associated to computed tomography (PET/CT) has been established as a standard tool in cancer evaluation. Being a multimodality imaging method, it combines in a single session the sensitivity granted by PET for detection of molecular targets within the picomolar range, with an underlying submilimetric resolution inherent to CT, that can precisely localize the PET findings. In this last decade, there have been new insights regarding the pathophysiology of atherosclerosis, particularly about plaque rupture and vascular remodeling. This has increased the interest for research on PET/CT in vascular diseases as a potential new diagnostic tool, since some PET molecular targets could identify diseases before the manifestation of gross anatomic features. In this review, we will describe the current applications of PET/CT in vascular diseases, emphasizing its usefulness in the settings of vasculitis, aneurysms, vascular graft infection, aortic dissection, and atherosclerosis/plaque vulnerability. Although not being properly peripheral vascular conditions, ischemic cardiovascular disease and cerebrovascular disease will be briefly addressed as well, due to their widespread prevalence and importance.

Atrial fibrillation and vascular disease-a bad combination

DEFF Research Database (Denmark)

Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

2012-01-01

This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...

Gene transfer therapy in vascular diseases.

Science.gov (United States)

McKay, M J; Gaballa, M A

2001-01-01

Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of

Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

NARCIS (Netherlands)

Kanhai, D.A.N.I.S.

2013-01-01

Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society,

Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

OpenAIRE

Kanhai, D.A.N.I.S.

2013-01-01

Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society, which is attributable to better disease awareness, better preventive strategies and better healthcare systems. As mortality rates are decreasing, the number of patients surviving their first vascul...

Anti-Inflammatory Effects of Interleukin-19 in Vascular Disease

Directory of Open Access Journals (Sweden)

Ross N. England

2012-01-01

Full Text Available Despite aggressive dietary modification, lipid-lowering medications, and other interventional medical therapy, vascular disease continues to be a leading cause of mortality in the western world. It is a significant medical and socioeconomic problem contributing to mortality of multiple diseases including myocardial infarction, stroke, renal failure, and peripheral vascular disease. Morbidity and mortality of vascular disease are expected to worsen with the increasing number of patients with comorbid conditions such as obesity, metabolic syndrome, and diabetes mellitus type 2. Vascular diseases such as atherosclerosis, restenosis, and allograft vasculopathy are recognized to be driven by inflammation, and as such, cytokines which mediate inflammation not only represent important targets of rational therapy, but also can be considered as possible therapeutic modalities themselves. In this paper, we will examine the role of inflammatory cytokines and lymphocyte Th1/Th2 polarity in vascular inflammation, with a focus on atherosclerotic vascular disease. We will then introduce a recently described Th2 interleukin, interleukin-19 (IL-19, as a previously unrecognized mediator of vascular inflammatory disorders. We will review our current understanding of this interleukin in health and disease and present the possibility that IL-19 could represent a potential therapeutic to combat vascular inflammatory disease.

Vascular disease in cocaine addiction.

Science.gov (United States)

Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

2017-07-01

Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation between blood and lymphatic vessel density and results of contrast-enhanced spectral mammography.

Science.gov (United States)

Luczynska, Elzbieta; Niemiec, Joanna; Ambicka, Aleksandra; Adamczyk, Agnieszka; Walasek, Tomasz; Ryś, Janusz; Sas-Korczyńska, Beata

2015-09-01

Contrast-enhanced spectral mammography (CESM) is a novel technique used for detection of tumour vascularity by imaging the moment in which contrast, delivered to the lesion by blood vessels, leaks out of them, and flows out through lymphatic vessels. In our study, we included 174 women for whom spectral mammography was performed for diagnostic purposes. The relationship between enhancement in CESM and blood vessel density (BVD), lymphatic vessel density (LVD) or the percentage of fields with at least one lymphatic vessel (distribution of podoplanin-positive vessels - DPV) and other related parameters was assessed in 55 cases. BVD, LVD and DPV were assessed immunohistochemically, applying podoplanin and CD31/CD34 as markers of lymphatic and blood vessels, respectively. The sensitivity (in detection of malignant lesions) of CESM was 100%, while its specificity - 39%. We found a significant positive correlation between the intensity of enhancement in CESM and BVD (p = 0.007, r = 0.357) and a negative correlation between the intensity of enhancement in CESM and DPV (p = 0.003, r = -0.390). Lesions with the highest enhancement in CESM showed a high number of blood vessels and a low number of lymphatics. 1) CESM is a method characterized by high sensitivity and acceptable specificity; 2) the correlation between CESM results and blood/lymphatic vessel density confirms its utility in detection of tissue angiogenesis and/or lymphangiogenesis.

Patterns of peripheral vascular diseases at Muhimbili National hospital

African Journals Online (AJOL)

diseases) and HIV- vasculitis. A total of 97 patients (63%) were surgically treated. Conclusion: Shortage of vascular surgeons and facilities in our. Country needs to be sorted out to save life to these patients with vascular disorders. Key Words: Peripheral Vascular Diseases, and Shortage of Vascular Services in Tanzania.

Nanomedicine approaches in vascular disease: a review.

Science.gov (United States)

Gupta, Anirban Sen

2011-12-01

Nanomedicine approaches have revolutionized the treatment of cancer and vascular diseases, where the limitations of rapid nonspecific clearance, poor biodistribution and harmful side effects associated with direct systemic drug administration can be overcome by packaging the agents within sterically stabilized, long-circulating nanovehicles that can be further surface-modified with ligands to actively target cellular/molecular components of the disease. With significant advancements in genetics, proteomics, cellular and molecular biology and biomaterials engineering, the nanomedicine strategies have become progressively refined regarding the modulation of surface and bulk chemistry of the nanovehicles, control of drug release kinetics, manipulation of nanoconstruct geometry and integration of multiple functionalities on single nanoplatforms. The current review aims to capture the various nanomedicine approaches directed specifically toward vascular diseases during the past two decades. Analysis of the promises and limitations of these approaches will help identify and optimize vascular nanomedicine systems to enhance their efficacy and clinical translation in the future. Nanomedicine-based approaches have had a major impact on the treatment and diagnosis of malignancies and vascular diseases. This review discusses various nanomedicine approaches directed specifically toward vascular diseases during the past two decades, highlighting their advantages, limitations and offering new perspectives on future applications. Copyright © 2011 Elsevier Inc. All rights reserved.

Expression and lymphatic microvessel density in primary tumors of node-neagtive colorectal cancer patients predict disease recurrence

NARCIS (Netherlands)

Doekhie, F.S.; Morreau, H.; de Bock, G.H.; Speetjens, F.M.; Dekker-Ensink, N.G.; Putter, H.; vand e Velde, C.J.H.; Tollenaar, R.A.E.M.; Kuppen, P.J.K.; Sialyl lewis, X.

2008-01-01

Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX),

Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

Science.gov (United States)

Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

2016-01-01

Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization

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Lee, Ji Yoon; Park, Changwon; Cho, Yong Pil; Lee, Eugine; Kim, Hyongbum; Kim, Pilhan; Yun, Seok H.; Yoon, Young-sup

2010-01-01

Background Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization. Methods and Results Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin+ cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin+ cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin+ cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin+ cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin+ cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role. Conclusions Our results provide compelling evidence that BM-derived podoplanin+ cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis. PMID:20855662

Diffuse and vascular hepatic diseases

International Nuclear Information System (INIS)

Kreimeyer, S.; Grenacher, L.

2011-01-01

In addition to focal liver lesions, diffuse and vascular disorders of the liver represent a wide spectrum of liver diseases which are from the radiological point of view often difficult or nearly impossible to diagnose. Classical diagnostic methods are computed tomography and magnetic resonance imaging in addition to ultrasound. Diffuse parenchymal damage caused by diseases of various etiologies is therefore difficult to evaluate because it often lacks characteristic morphological features. For hepatic steatosis, hemochromatosis/siderosis as an example of a diffuse storage disease and sarcoidosis and candidiasis as infectious/inflammatory diseases, an image-based diagnosis is appropriate in some cases. For most diffuse liver diseases, however only nonspecific changes are visualized. Vascular pathologies of the liver, such as the Budd-Chiari syndrome and portal vein thrombosis, however, can usually be diagnosed very clearly using radiology and there is also a very effective interventional radiological treatment. Chronic diseases very often culminate in liver cirrhosis which is highly associated with an increased risk of liver cancer. (orig.) [de

Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

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Barton, Matthias; Husmann, Marc; Meyer, Matthias R

2016-05-01

Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

A novel podoplanin-GFPCre mouse strain for gene deletion in lymphatic endothelial cells.

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Gil, Hyea Jin; Ma, Wanshu; Oliver, Guillermo

2018-04-01

The lymphatic vascular system is a one-direction network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells responsible for maintaining fluid homeostasis. Some of the main functions of the lymphatic vasculature are to drain fluid from the extracellular spaces and return it back to the blood circulation, lipid absorption from the intestinal tract, and transport of immune cells to lymphoid organs. A number of genes controlling the development of the mammalian lymphatic vasculature have been identified in the last few years, and their functional roles started to be characterized using gene inactivation approaches in mice. Unfortunately, only few mouse Cre strains relatively specific for lymphatic endothelial cells (LECs) are currently available. In this article, we report the generation of a novel Podoplanin (Pdpn) GFPCre transgenic mouse strain using its 5' regulatory region. Pdpn encodes a transmembrane mucin-type O-glycoprotein that is expressed on the surface of embryonic and postnatal LECs, in addition to few other cell types. Our detailed characterization of this novel strain indicates that it will be a valuable additional genetic tool for the analysis of gene function in LECs. © 2018 Wiley Periodicals, Inc.

Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

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Lohrberg, Melanie; Pabst, Reinhard; Wilting, Jörg

2018-01-25

The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

Science.gov (United States)

Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

2015-12-07

To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

Investigation of intratumoural and peritumoural lymphatics expressed by podoplanin and LYVE-1 in the hybridoma-induced tumours

Science.gov (United States)

Ji, RC; Eshita, Y; Kato, S

2007-01-01

Tumour-associated lymphatics contribute to a key component of metastatic spread, however, the biological interaction of tumour cells with intratumoural and peritumoural lymphatics (ITLs and PTLs) has remained unclear. To address this important issue, we have focused on the morphological and molecular aspects of newly formed lymphatics (lymphangiogenesis) and pre-existing lymphatics in the intratumoural and peritumoural tissues by using a hybridoma-induced tumour model. In the present study, ITLs with very high vessel density within the tumour mass showed small and flattened contours that varied from non-solid-to-solid tumours, whereas PTLs were relatively disorganized and tortuous, and packed with a cluster of tumour cells at the tumour periphery. Lymphatic endothelial cells (LECs) both in ITLs and PTLs were expressed with LYVE-1 and podoplanin in various tumour tissues, in which initial lymphatics were extremely extended and dilated. The tumour cells were frequently detected adhering to or penetrating lymphatic walls, especially near the open junctions. In the metastatic tissues, lymphangiogenic vasculatures occurred within the tumour matrix, and collecting PTLs represented abnormal twisty valve leaflets. The Western blot and RT-PCR analysis showed local variations of LEC proliferating potentials and lymphatic involvement in metastasis by a distinct profile of the protein and mRNA expression by LYVE-1, podoplanin, Prox-1 and vascular endothelial growth factor-3 (VEGFR-3). These findings indicated that both ITLs and PTLs, including enlarged pre-existing and newly formed lymphatics, may play a crucial role in metastasis with an active tumour cell adhesion, invasion, migration and implantation. PMID:17696907

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

Science.gov (United States)

Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

2015-01-01

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

Pdgfrb-Cre targets lymphatic endothelial cells of both venous and non-venous origins.

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Ulvmar, Maria H; Martinez-Corral, Ines; Stanczuk, Lukas; Mäkinen, Taija

2016-06-01

The Pdgfrb-Cre line has been used as a tool to specifically target pericytes and vascular smooth muscle cells. Recent studies showed additional targeting of cardiac and mesenteric lymphatic endothelial cells (LECs) by the Pdgfrb-Cre transgene. In the heart, this was suggested to provide evidence for a previously unknown nonvenous source of LECs originating from yolk sac (YS) hemogenic endothelium (HemEC). Here we show that Pdgfrb-Cre does not, however, target YS HemEC or YS-derived erythro-myeloid progenitors (EMPs). Instead, a high proportion of ECs in embryonic blood vessels of multiple organs, as well as venous-derived LECs were targeted. Assessment of temporal Cre activity using the R26-mTmG double reporter suggested recent occurrence of Pdgfrb-Cre recombination in both blood and lymphatic ECs. It thus cannot be excluded that Pdgfrb-Cre mediated targeting of LECs is due to de novo expression of the Pdgfrb-Cre transgene or their previously established venous endothelial origin. Importantly, Pdgfrb-Cre targeting of LECs does not provide evidence for YS HemEC origin of the lymphatic vasculature. Our results highlight the need for careful interpretation of lineage tracing using constitutive Cre lines that cannot discriminate active from historical expression. The early vascular targeting by the Pdgfrb-Cre also warrants consideration for its use in studies of mural cells. genesis 54:350-358, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.

Castleman's disease: A rare indication for endovascular therapy for hemoptysis

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Mohammad A Husainy

2017-01-01

Full Text Available Castleman's disease (CD is a rare lympho-proliferative disorder due to faulty immune regulation resulting in proliferation of lymphatic tissue. The vascular supply to these lesions have been reported to arise from the bronchial, internal mammary and the intercostal arteries. We report a case of hemoptysis secondary to intrathoracic CD with vascular supply arising from the left inferior phrenic artery which was successfully embolised with polyvinyl alcohol (PVA particles.

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

Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

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R Anuradha

Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

Current concepts in the classification, diagnosis and treatment of vascular anomalies

International Nuclear Information System (INIS)

Ernemann, Ulrike; Kramer, Ulrich; Miller, Stephan; Bisdas, Sotirios; Rebmann, Hans; Breuninger, Helmut; Zwick, Christine; Hoffmann, Juergen

2010-01-01

Patients with extended vascular anomalies may suffer from significant aesthetic and functional impairment and represent a challenge to therapeutic planning, which is best met by an interdisciplinary concept. In agreement with the International Society for the Study of Vascular Anomalies (ISSVA), vascular lesions are classified into haemangiomas as proliferating endothelial tumours on the one hand and congenital vascular malformations on the other. According to the preponderant vascular channels and hemodynamic characteristics, malformations are subdivided into low flow (venous, lymphatic and capillary) lesions and high-flow malformations. Diagnostic imaging should be targeted at the specific structural and functional informations required for treatment planning. The imaging modality of choice to provide these informations is magnetic resonance imaging (MRI) supplemented by magnetic resonance angiography (MRA) with high spatial and temporal resolution. Treatment indications for haemangiomas depend on the proliferative behaviour of the lesion and comprise β-blockers in order to induce involution as well as cryotherapy, laser and open surgery. Interventional radiological procedures have evolved as an essential element in an interdisciplinary treatment plan for vascular malformations and include percutaneous sclerotherapy with ethanol and OK-432 for venous and lymphatic malformations and transarterial embolization for high-flow lesions.

Current concepts in the classification, diagnosis and treatment of vascular anomalies

Energy Technology Data Exchange (ETDEWEB)

Ernemann, Ulrike, E-mail: ulrike.ernemann@med.uni-tuebingen.d [Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Kramer, Ulrich; Miller, Stephan [Department of Diagnostic and Interventional Radiology, Radiological Clinic, University Hospital Tuebingen (Germany); Bisdas, Sotirios [Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Rebmann, Hans [Department of Paediatrics, Children' s Hospital, University Hospital Tuebingen (Germany); Breuninger, Helmut [Department of Dermatology, University Hospital Tuebingen (Germany); Zwick, Christine [Department of Hand, Plastic, Reconstructive and Burns Surgery, BG Trauma Clinic Tuebingen, University Hospital Tuebingen (Germany); Hoffmann, Juergen [Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen (Germany)

2010-07-15

Patients with extended vascular anomalies may suffer from significant aesthetic and functional impairment and represent a challenge to therapeutic planning, which is best met by an interdisciplinary concept. In agreement with the International Society for the Study of Vascular Anomalies (ISSVA), vascular lesions are classified into haemangiomas as proliferating endothelial tumours on the one hand and congenital vascular malformations on the other. According to the preponderant vascular channels and hemodynamic characteristics, malformations are subdivided into low flow (venous, lymphatic and capillary) lesions and high-flow malformations. Diagnostic imaging should be targeted at the specific structural and functional informations required for treatment planning. The imaging modality of choice to provide these informations is magnetic resonance imaging (MRI) supplemented by magnetic resonance angiography (MRA) with high spatial and temporal resolution. Treatment indications for haemangiomas depend on the proliferative behaviour of the lesion and comprise {beta}-blockers in order to induce involution as well as cryotherapy, laser and open surgery. Interventional radiological procedures have evolved as an essential element in an interdisciplinary treatment plan for vascular malformations and include percutaneous sclerotherapy with ethanol and OK-432 for venous and lymphatic malformations and transarterial embolization for high-flow lesions.

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.

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

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Philipp Steven

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

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.

Data base management system for lymphatic filariasis--a neglected tropical disease.

Science.gov (United States)

Upadhyayula, Suryanaryana Murty; Mutheneni, Srinivasa Rao; Kadiri, Madhusudhan Rao; Kumaraswamy, Sriram; Nelaturu, Sarat Chandra Babu

2012-01-01

Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. This database application is developed using Model View Controller (MVC) architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

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...

Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-α in suppressing remodeling of blood vessels and lymphatics in airway inflammation.

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Le, Catherine T K; Laidlaw, Grace; Morehouse, Christopher A; Naiman, Brian; Brohawn, Philip; Mustelin, Tomas; Connor, Jane R; McDonald, Donald M

2015-11-01

Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both together completely prevented these changes. Genome-wide analysis of changes in gene expression revealed synergistic actions of the antibody combination over a broad range of genes and signaling pathways involved in inflammatory responses. These findings demonstrate that Ang2 and TNF are essential and synergistic drivers of remodeling of blood vessels and lymphatics during the initial stage of inflammation after infection. Inhibition of Ang2 and TNF together results in widespread suppression of the inflammatory response. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Mechanisms of lymphatic regeneration after tissue transfer.

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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.

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

Science.gov (United States)

Tsuchimoto, Akihiro; Nakano, Toshiaki; Hasegawa, Shoko; Masutani, Kosuke; Matsukuma, Yuta; Eriguchi, Masahiro; Nagata, Masaharu; Nishiki, Takehiro; Kitada, Hidehisa; Tanaka, Masao; Kitazono, Takanari; Tsuruya, Kazuhiko

2017-08-01

Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized β = -0.30, P = 0.019). High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

T cells in vascular inflammatory diseases

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Lucas L Lintermans

2014-10-01

Full Text Available Inflammation of the human vasculature is a manifestation of many different diseases ranging from systemic autoimmune diseases to chronic inflammatory diseases, in which multiple types of immune cells are involved. For both autoimmune diseases and chronic inflammatory diseases several observations support a key role for T lymphocytes in these disease pathologies, but the underlying mechanisms are poorly understood. Previous studies in several autoimmune diseases have demonstrated a significant role for a specific subset of CD4+ T cells termed effector memory T cells. This expanded population of effector memory T cells may contribute to tissue injury and disease progression. These cells exert multiple pro-inflammatory functions through the release of effector cytokines. Many of these cytokines have been detected in the inflammatory lesions and participate in the vasculitic reaction, contributing to recruitment of macrophages, neutrophils, dendritic cells, NK cells, B cells and T cells. In addition, functional impairment of regulatory T cells paralyzes anti-inflammatory effects in vasculitic disorders. Interestingly, activation of effector memory T cells in uniquely dependent on the voltage-gated Kv1.3 potassium channel providing an anchor for specific drug targeting. In this review, we focus on the CD4+ T cells in the context of vascular inflammation and describe the evidence supporting the role of different T cell subsets in vascular inflammation. Selective targeting of pathogenic effector memory T cells might enable a more tailored therapeutic approach that avoids unwanted adverse side effects of generalized immunosuppression by modulating the effector functions of T cell responses to inhibit the development of vascular inflammation.

How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

OpenAIRE

Stone, C.; Lindsay, S.W.; Chitnis, N.

2014-01-01

Background: The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between th...

Vascular pathology: Cause or effect in Alzheimer disease?

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Rius-Pérez, S; Tormos, A M; Pérez, S; Taléns-Visconti, R

2018-03-01

Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Is Pseudoexfoliation Syndrome a Risk Factor for Cerebro Vascular Disease?

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Kan, Emrah; Yılmaz, Ahmet; Demirağ, Mehmet Derya; Çalık, Murat

2017-01-01

To determine the relationship between cerebro vascular disease and pseudoexfoliation syndrome. This cross-sectional case control study consisted of 50 patients with ischemic-type cerebro vascular disease and 50 control subjects. All subjects were investigated for diabetes mellitus and hypertension status and underwent a detailed ophthalmic examination. A diagnosis of pseudoexfoliation syndrome was made if characteristic greyish particulate matter was found on the anterior lens capsule after pupillary dilatation by slit-lamp examination. All subjects were compared in terms of pseudoexfoliation syndrome, diabetes mellitus, and hypertension. Pearson Chi Square and Student's t test were used for statistical analysis. Logistic regression analyses of the risk factors between groups were also made. The presence of pseudoexfoliation syndrome was significantly higher in patients with cerebro vascular disease when compared to the control subjects (p = 0.02). The frequency of diabetes mellitus was similar between the two groups. Arterial hypertension was significantly more frequent in the patient group when compared to the control subjects (p cerebro vascular disease. In the present study, we found that pseudoexfoliation syndrome frequency was found to be higher in patients with cerebro vascular disease than in control subjects. A slit-lamp examination of the eye could be an important marker that indicates the risk of cerebro vascular disease. We recommend an evaluation of all subjects with pseudoexfoliation syndrome for the presence of cerebro vascular disease. Longitudinal studies with larger populations are needed to confirm this relationship.

[Menopause: Hypertension and vascular disease].

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Zilberman, J M

Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

International Nuclear Information System (INIS)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An; Olivera, Gustavo; Somlo, George

2007-01-01

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk

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

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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.

Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.

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Absinta, Martina; Ha, Seung-Kwon; Nair, Govind; Sati, Pascal; Luciano, Nicholas J; Palisoc, Maryknoll; Louveau, Antoine; Zaghloul, Kareem A; Pittaluga, Stefania; Kipnis, Jonathan; Reich, Daniel S

2017-10-03

Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.

Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease.

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Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A; Kappelle, L Jaap; de Borst, Gert Jan; Cramer, Maarten J; Visseren, Frank L J; Aboyans, Victor; Westerink, Jan

2017-10-01

Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Perceptions, knowledge, attitudes and practices for the prevention and control of lymphatic filariasis in Conakry, Republic of Guinea.

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Kouassi, Bernard L; Barry, Aboulaye; Heitz-Tokpa, Kathrin; Krauth, Stefanie J; Goépogui, Andre; Baldé, Mamadou S; Barry, Oumar; Niamey, Marie L; Bockarie, Moses J; Koudou, Benjamin G; Utzinger, Jürg

2018-03-01

Little is known about the perceptions, attitudes and practices of lymphatic filariasis in Conakry, Republic of Guinea. Yet, such knowledge is important for an optimal design and implementation of setting-specific prevention and control measures. We conducted a cross-sectional study using a mixed methods approach. Qualitative data related to people's general experience with lymphatic filariasis, their perception of the causes of the disease, the onset of elephantiasis, care-seeking behaviour and the socioeconomic impact of lymphatic filariasis were collected through in-depth interviews with 85 respondents. Quantitative data related to strategies for prevention and the knowledge of the causes of the disease were collected by interviewing 429 people. A total of 514 individuals (313 females and 201 males), aged 10-84 years, participated. Most participants were well aware of lymphatic filariasis and they recognized the disease mainly by its disfiguring manifestation, collectively termed "elephantiasis" or "leg-swelling disease". Morbidity patterns due to filarial infection showed an increase with age (from 30 to 50 years) independent of sex. Most patients with lymphatic filariasis abandoned their jobs (73.9%) or sought other work (21.7%). The main perceived causes of acquiring lymphatic filariasis were of supernatural origin (as stated by 8.7% of patients and 5.7% of healthy subjects), while mosquito bites were mentioned by fewer participants (4.3% of patients and 4.2% of healthy subjects). A number of other causes were reported that relate to both medical and non-medical conceptions. The study also identified socioeconomic impairments and stigmatization due to elephantiasis. Taken together, community perception of lymphatic filariasis in Conakry is influenced by sociocultural conceptions. Appropriate health education campaigns aimed at enhancing community understanding of the transmission of lymphatic filariasis are required to increase the success of mass drug

Data base management system for lymphatic filariasis--a neglected tropical disease.

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Suryanaryana Murty Upadhyayula

Full Text Available BACKGROUND: Researchers working in the area of Public Health are being confronted with large volumes of data on various aspects of entomology and epidemiology. To obtain the relevant information out of these data requires particular database management system. In this paper, we have described about the usages of our developed database on lymphatic filariasis. METHODS: This database application is developed using Model View Controller (MVC architecture, with MySQL as database and a web based interface. We have collected and incorporated the data on filariasis in the database from Karimnagar, Chittoor, East and West Godavari districts of Andhra Pradesh, India. CONCLUSION: The importance of this database is to store the collected data, retrieve the information and produce various combinational reports on filarial aspects which in turn will help the public health officials to understand the burden of disease in a particular locality. This information is likely to have an imperative role on decision making for effective control of filarial disease and integrated vector management operations.

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

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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.

Up-Regulation of the Lymphatic Marker Podoplanin, a Mucin-Type Transmembrane Glycoprotein, in Human Squamous Cell Carcinomas and Germ Cell Tumors

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Schacht, Vivien; Dadras, Soheil S.; Johnson, Louise A.; Jackson, David G.; Hong, Young-Kwon; Detmar, Michael

2005-01-01

The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses. We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs. These findings were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied. These findings suggest a potential role of podoplanin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers. PMID:15743802

MR imaging of edematous limbs in lymphatic and nonlymphatic edema

International Nuclear Information System (INIS)

Fujii, K.

1994-01-01

To evaluate the role of MR imaging in the diagnosis of edema, various types of edema were examined with MR imaging. MR imaging of edematous limbs was performed on 60 patients (lymphatic edema 48, nonlymphatic edema 12) using. T1-and T2-weighted spin-echo and shot inversion time inversion recovery sequences. Thickness and signal intensity of the cutis, subcutis and subfascia were evaluated in the images. In all 48 cases with lymphatic edema, trabecular structures suggesting dilated collateral lymphatic vessels were observed in the swollen subcutis. Two cases with nephrotic syndrome showed similar findings. In 6 cases with venous edema, fatty intensity was found in the subfascia. In the remaining 4 cases, the subcutis exhibited only water intensity. MR imaging is a potential contributor to the diagnosis of various edematous diseases. (orig./MG)

HMGB1 in vascular diseases : Its role in vascular inflammation and atherosclerosis

NARCIS (Netherlands)

de Souza, A. W. S.; Westra, J.; Limburg, P. C.; Bijl, M.; Kallenberg, C. G. M.

2012-01-01

The nuclear protein high mobility group box 1 (HMGB1) has been suggested to be involved in the pathogenesis of several vascular diseases such as systemic vasculitis and atherosclerosis. In systemic vasculitides including ANCA-associated vasculitis and Kawasaki disease, serum HMGB1 levels are higher

Non-endemic cases of lymphatic filariasis.

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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.

Lymphatic filariasis among the Yakurr people of Cross River State, Nigeria

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Iboh Cletus I

2012-09-01

Full Text Available Abstract Background In order to initiate a disease elimination programme for lymphatic filariasis based on mass drug administration, a proper understanding of the geographical distribution and degree of risk is essential. Methods An investigation of lymphatic filariasis due to Wuchereria bancrofti was carried out among 785 people in four communities of Yakurr Local Government Area of Cross River State, Nigeria between March and August, 2009. Finger prick blood smear samples collected from the subjects were examined for W. bancrofti using standard parasitological protocol. The subjects were also screened for clinical manifestations of lymphatic filariasis. Results Of the 785 persons examined, 48 (6.1% were positive for microfilariae in their thick blood smear. There was a significant difference in the prevalence of lymphatic filariasis among the various age groups (P  0.05. The overall mean microfilarial density of the infected individuals was 5.6mf/50 μl. There was a significant variation (P  Conclusions The National Lymphatic Filariasis Elimination Programme should intervene by expanding the distribution of albendazole and ivermectin to all endemic areas including Yakurr Local Government Area of Cross River State, Nigeria.

Major lipids, apolipoproteins, and risk of vascular disease

DEFF Research Database (Denmark)

Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem

2009-01-01

CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...

Individualized Vascular Disease Prevention in High-Risk Patients

NARCIS (Netherlands)

Kaasenbrood, L

2016-01-01

In the pharmacologic prevention of vascular events, clinicians need to translate average effects from a clinical trial to the individual patient. Prediction models can contribute to individualized vascular disease prevention by selecting patients for treatment based on estimated risk or expected

Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node.

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Srinivasan, Swetha; Vannberg, Fredrik O; Dixon, J Brandon

2016-04-18

It is well documented that cells secrete exosomes, which can transfer biomolecules that impact recipient cells' functionality in a variety of physiologic and disease processes. The role of lymphatic drainage and transport of exosomes is as yet unknown, although the lymphatics play critical roles in immunity and exosomes are in the ideal size-range for lymphatic transport. Through in vivo near-infrared (NIR) imaging we have shown that exosomes are rapidly transported within minutes from the periphery to the lymph node by lymphatics. Using an in vitro model of lymphatic uptake, we have shown that lymphatic endothelial cells actively enhanced lymphatic uptake and transport of exosomes to the luminal side of the vessel. Furthermore, we have demonstrated a differential distribution of exosomes in the draining lymph nodes that is dependent on the lymphatic flow. Lastly, through endpoint analysis of cellular distribution of exosomes in the node, we identified macrophages and B-cells as key players in exosome uptake. Together these results suggest that exosome transfer by lymphatic flow from the periphery to the lymph node could provide a mechanism for rapid exchange of infection-specific information that precedes the arrival of migrating cells, thus priming the node for a more effective immune response.

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

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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.

Control of Vascular Streak Dieback Disease of Cocoa with Flutriafol Fungicides

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Febrilia Nur'aini

2014-12-01

Full Text Available Vascular streak dieback caused by the fungus Oncobasidium theobromae is one of the important diseases in cocoa crop in Indonesia. One approach to control the disease is by using fungicides. The aim of this research was to determine the effect of class triazole fungicides to the intensity of the vascular streak dieback disease on cocoa seedling phase, immature and mature cocoa. Experiments were conducted in Kotta Blater, PTPN XII and Kaliwining, Indonesian  Coffee and Cocoa Research Institute. Flutriafol 250 g/l with a concentration 0,05%, 0,1% and 0,15% foliar sprayed on cocoa seedlings, immature and mature cocoa. Active compound combination of Azoxystrobin and Difenoconazole with 0,1% concentration used as a comparation fungicides. The result showed that Flutriafol with 0,05%, 0,1% and 0,15% concentration and Azoxystrobin & Difenoconazol with 0,1% concentration could suppress the vascular streak dieback disease on seedlings. On immature plants, the application of Flutriafol was not effectively suppress the vascular streak dieback disease whereas the fungicide comparison could suppress with the efficacy level of 46.22%. On mature plants,both of fungicides could not suppress the vascular streak dieback disease. Key words: Fungicide, cocoa, vascular streak dieback, triazole, flutriafol, azoxystrobin+difenoconazol

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.

Sclerotherapy for Benign Cystic Diseases in the Neck

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Kim, Ji Hoon; Sohn, Chul Ho; Choi, Seung Hong; Yun, Tae Jin [Dept. of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2012-08-15

Surgery has been the classic treatment of choice for benign cystic diseases, including lymphatic malformation, ranula, branchial cleft cyst, thyroglossal duct cyst, thyroid cyst, parathyroid cyst, and lymphocele. However, surgery is associated with a tendency toward recurrence and may be accompanied by various complications, such as nerve injuries, vascular injuries, and scar formation. Therefore, sclerotherapy using various agents has been applied successfully to treatment of benign cystic diseases in the neck. This editorial reviews the use of various sclerotic agents and application of sclerotherapy to benign cystic diseases in the neck.

Sclerotherapy for Benign Cystic Diseases in the Neck

International Nuclear Information System (INIS)

Kim, Ji Hoon; Sohn, Chul Ho; Choi, Seung Hong; Yun, Tae Jin

2012-01-01

Surgery has been the classic treatment of choice for benign cystic diseases, including lymphatic malformation, ranula, branchial cleft cyst, thyroglossal duct cyst, thyroid cyst, parathyroid cyst, and lymphocele. However, surgery is associated with a tendency toward recurrence and may be accompanied by various complications, such as nerve injuries, vascular injuries, and scar formation. Therefore, sclerotherapy using various agents has been applied successfully to treatment of benign cystic diseases in the neck. This editorial reviews the use of various sclerotic agents and application of sclerotherapy to benign cystic diseases in the neck.

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

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Hu, Xiaoming; De Silva, T. Michael; Chen, Jun; Faraci, Frank M.

2017-01-01

The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events. PMID:28154097

Lymphatic microangiopathy of the skin in systemic sclerosis.

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Leu, A J; Gretener, S B; Enderlin, S; Brühlmann, P; Michel, B A; Kowal-Bielecka, O; Hoffmann, U; Franzeck, U K

1999-03-01

The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

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.

Interplay between coagulation and vascular inflammation in sickle cell disease

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Sparkenbaugh, Erica; Pawlinski, Rafal

2013-01-01

Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease. PMID:23593937

A case with post-irradiation cerebral vascular disease accompanied by Cushing's disease

International Nuclear Information System (INIS)

Shinoda, Keiichi; Kuriyama, Takanobu; Kimura, Fumiharu; Kawamura, Hiroshi; Takamatsu, Junta; Mozai, Toshiji

1986-01-01

A 37-year-old man with Cushing's disease developed cerebral infarction 13 years after Co-60 irradiation of a total dose of 60 Gy for pituitary adenoma. Cerebral angiography showed stenosis or occlusion of the bilateral carotid arteries and basilar artery which were in the radiation fields. A basophilic adenoma was resected, and symptoms of Cushing's disease have resolved. The vascular lesions are likely to be not only radiation-induced, but also stimulated by hyperlipemia and hypertension associated with Cushing's disease. It is recommended to eliminate factors, such as hyperlipemia and hypertension, stimulatig vascular damage in the management of patients treated with radiation therapy. The relevant literature is reviewed. (Namekawa, K.)

Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction.

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Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

2012-02-01

Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, 'premature' vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using 'endothelial therapy' aiming at maintaining or restoring vascular endothelial health. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

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Khalil, Raouf A

2013-12-15

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

Lymphatic System Flows

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Moore, James E., Jr.; Bertram, Christopher D.

2018-01-01

The supply of oxygen and nutrients to tissues is performed by the blood system and involves a net leakage of fluid outward at the capillary level. One of the principal functions of the lymphatic system is to gather this fluid and return it to the blood system to maintain overall fluid balance. Fluid in the interstitial spaces is often at subatmospheric pressure, and the return points into the venous system are at pressures of approximately 20 cmH2O. This adverse pressure difference is overcome by the active pumping of collecting lymphatic vessels, which feature closely spaced one-way valves and contractile muscle cells in their walls. Passive vessel squeezing causes further pumping. The dynamics of lymphatic pumping have been investigated experimentally and mathematically, revealing complex behaviors that indicate that the system performance is robust against minor perturbations in pressure and flow. More serious disruptions can lead to incurable swelling of tissues called lymphedema.

Noninvasive studies of peripheral vascular disease

International Nuclear Information System (INIS)

Yao, J.S.T.

1987-01-01

Plethysmography probably is the oldest method for measuring blood flow. In this method, measurements are made of changes in volume of an organ or region of tissue. In the modern practice of vascular surgery, the use of plethysmography has been expanded to include detection of not only arterial occlusive disease but also carotid artery disease and venous problems. Several types of plethysmographs are now available for clinical use in the evaluation of arterial occlusions. These are volume, strain-gauge, and photoelectric plethysmographs. The water-filled volume recorder, popular in the early use of plethysmography, is now obsolete and has been replaced by the air-filled volume plethysmograph, notably, the pulse-volume recorder. For clinical application, the newer plethysmographs, such as the strain-gauge, photopletyhsmograph, and pulse-volume recorder, are now standard equipment in many vascular laboratories. They are discussed in this article

Lymphatic flow in humans as indicated by the clearance of 125I-labeled albumin from the subcutaneous tissue of the leg

International Nuclear Information System (INIS)

Fernandez, M.J.; Davies, W.T.; Owen, G.M.; Tyler, A.

1983-01-01

Since the removal of albumin from the extracellular space and its return to the vascular compartment is the essential function of the lymphatic system, the rate at which it is removed from the interstitial tissue may be regarded as a means of estimating lymphatic efficiency. An objective measure of lymphatic function can be obtained by monitoring the rate of clearance following injection of 125 I-labeled albumin (RIHSA) from the subcutaneous tissue of a limb. The clearance of 125 I-RIHSA from lower limb was monitored in a group of patients with normal limbs, patients with unilateral edema due to deep vein thrombosis, and patients with bilateral edema due to hypoproteinemia. The mean T1/2 in normal legs was 32.7 hr, compared to 23.7 hr in edematous limbs due to deep vein thrombosis and 19.4 in edematous limbs due to hypoproteinemia. There is a clear-cut difference in clearance rate between edematous and nonedematous limbs. This suggests that lymphatic flow is increased in edema due to venous obstruction and hypoproteinemia

Lymphatic drainage of lung segments in the visceral pleura: a cadaveric study.

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Fourdrain, Alex; Lafitte, Sophie; Iquille, Jules; De Dominicis, Florence; Havet, Eric; Peltier, Johann; Bagan, Patrick; Berna, Pascal

2018-01-01

Although peribronchial lymphatic drainage of the lung has been well characterized, lymphatic drainage in the visceral pleura is less well understood. The objective of the present study was to evaluate the lymphatic drainage of lung segments in the visceral pleura. Adult, European cadavers were examined. Cadavers with a history of pleural or pulmonary disease were excluded. The cadavers had been refrigerated but not embalmed. The lungs were surgically removed and re-warmed. Blue dye was injected into the subpleural area and into the first draining visceral pleural lymphatic vessel of each lung segment. Twenty-one cadavers (7 males and 14 females; mean age 80.9 years) were dissected an average of 9.8 day postmortem. A total of 380 dye injections (in 95 lobes) were performed. Lymphatic drainage of the visceral pleura followed a segmental pathway in 44.2% of the injections (n = 168) and an intersegmental pathway in 55.8% (n = 212). Drainage was found to be both intersegmental and interlobar in 2.6% of the injections (n = 10). Lymphatic drainage in the visceral pleura followed an intersegmental pathway in 22.8% (n = 13) of right upper lobe injections, 57.9% (n = 22) of right middle lobe injections, 83.3% (n = 75) of right lower lobe injections, 21% (n = 21) of left upper lobe injections, and 85.3% (n = 81) of left lower lobe injections. In the lung, lymphatic drainage in the visceral pleura appears to be more intersegmental than the peribronchial pathway is-especially in the lower lobes. The involvement of intersegmental lymphatic drainage in the visceral pleura should now be evaluated during pulmonary resections (and especially sub-lobar resections) for lung cancer.

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

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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

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

International Nuclear Information System (INIS)

Short, Robert F.; Shiels, William E.; Sferra, Thomas J.; Nicol, Kathleen K.; Schofield, Minka; Wiet, Gregory J.

2007-01-01

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

Chapter 20. Lymphatic system

International Nuclear Information System (INIS)

Meyniel, G.; Plagne, R.; Veyre, A.

1975-01-01

It is recalled than in isotopic lymphography the tracer may be introduced into the lymphatic system by two methods: direct lymphography when the product is injected directly into a lymphatic vessel or lymph node, indirect lymphography when the product is injected into interstitial tissues, taken up by the lymph flow and fixed by the glands. The disadvantages of the direct method at present restrict the radioisotopic exploration of the lymphatic system to indirect lymphography. This technique, whereby the lymphatic draining of the tracer injection zone may be followed, is described. The use of metallic colloids (Au-198, In-111, Tc-99m) fixed by the glands gives a sharp and lasting contrast, but also possesses disadvantages. The conditions required of a selective tracer are examined and the possibilities of various types of molecules for this study estimated. In spite of undeniable disadvantages the colloids of technetium-99m are being used more and more because of the quality of the images obtained. The results are interpreted and the chief indications of the method defined. The therapeutic possibilities of isotopic lymphography are also shown [fr

Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

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Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

2010-03-01

White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

Vascular endothelial growth factors and angiogenesis in eye disease

NARCIS (Netherlands)

Witmer, A. N.; Vrensen, G. F. J. M.; van Noorden, C. J. F.; Schlingemann, R. O.

2003-01-01

The vascular endothelial growth factor (VEGF) family of growth factors controls pathological angiogenesis and increased vascular permeability in important eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). The purpose of this review is to develop new insights

Evaluation and percutaneous management of atherosclerotic peripheral vascular disease

International Nuclear Information System (INIS)

Widlus, D.M.; Osterman, F.A. Jr.

1989-01-01

Atherosclerotic peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass. Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high. Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation and nonoperative management of PVD, with an emphasis on the newer modalities of management presently being investigated

Diagnostics of vascular diseases as a cause for acute abdomen

International Nuclear Information System (INIS)

Juchems, M.S.; Aschoff, A.J.

2010-01-01

Vascular pathologies are rare causes of an acute abdomen. If the cause is a vascular disease a rapid diagnosis is desired as vascular pathologies are associated with high mortality. A differentiation must be made between arterial and venous diseases. An occlusion of the superior mesenteric artery is the most common reason for acute mesenteric ischemia but intra-abdominal arterial bleeding is also of great importance. Venous pathologies include thrombotic occlusion of the portal vein, the mesenteric vein and the vena cava. Multi-detector computed tomography (MDCT) is predestined for the diagnostics of vascular diseases of the abdomen. Using multiphasic contrast protocols enables reliable imaging of the arterial and venous vessel tree and detection of disorders with high sensitivity and specificity. Although conventional angiography has been almost completely replaced by MDCT as a diagnostic tool, it is still of high importance for minimally invasive interventions, for example in the management of gastrointestinal bleeding. (orig.) [de

Investigations of lymphatic drainage from the interstitial space

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Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

2017-11-01

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

Neuropsychiatric symptoms in patients with Alzheimer’s disease with a vascular component

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Mariola Bidzan

2014-06-01

Full Text Available objective. Vascular changes are observed in most cases of Alzheimer’s disease (AD. Observations of AD and vascular disease (VD allow us to surmise that vascular changes may not only affect cognitive impairment in AD but may also have a negative influence on the neuropsychiatric symptoms which often occur in the course of the disease. The aim of the study was to evaluate the impact of vascular factors on the neuropsychiatric symptoms in Alzheimer’s Disease. material and methods. The study included 48 people with a preliminary diagnosis of Alzheimer’s Disease on the basis of NINCDS/ADRDA criteria. The evaluation of impairments in cognitive functioning was carried out by means of the Alzheimer Disease Assessment Scale – the cognitive part (ADAS – cog, whereas the behavioural and psychological symptoms were evaluated by means of the Neuropsychiatric Inventory – the version adapted for residents of nursing homes for the elderly (Neuropsychiatric Inventory – Nursing Home Version (NPI – NH. The score on the Hachinski scale was the basis for dividing the study participants into two groups – those with a mild vascular component (0–1 points on the Hachinski scale and those with a severe vascular component (2–4 points. results. The analyzed groups did not differ with respect to the intensity of cognitive impairments (ADAS-cog or age of the participants. Scores obtained on the NPI – NH scale as well as some of its elements (depression/dysphoria and anxiety had a discriminating value. Studies show that vascular factors are a serious risk factor for neuropsychiatric symptoms in AD. conclusions. Vascular factors in Alzheimer’s Disease influence the presence of neuropsychiatric symptoms. In the course of angiogenic dementia a greater frequency in depressive disorders was shown. The most visible differences between individuals with a greater and lesser burden of vascular factors was in the realm of depressive and dysphoric disorders.

An interesting case of peripheral vascular disease, vascular reperfusion, and subsequent development of pain due to Paget's disease of bone.

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Kwun, Sunna; Tucci, Joseph R

2013-01-01

To present a case of Paget's disease of bone that was unmasked after vascular reperfusion. In this case study, we review the presentation, evaluation, diagnosis, and management of a patient with Paget's disease and peripheral vascular disease. A 79-year-old-woman with a history of coronary artery heart disease and recent finding of a T5 compression fracture was hospitalized for evaluation of right lower extremity claudication. Angiography demonstrated a focal complete occlusion of the distal right femoral and popliteal arteries. A self-expanding stent was placed in the distal femoral and popliteal arteries. Approximately 48 hours after the procedure, the patient developed severe, right lower leg pain. On endocrine evaluation, the patient was found to have clinical signs suggesting Paget's disease of bone, which was subsequently confirmed by imaging. This patient's development of severe pain following reperfusion of distal femoral and popliteal arteries is in keeping with the known and aforementioned hypervascularity of pagetic bone. The finding of increased warmth over an area of skeletal deformation should always raise the possibility of Paget's disease of bone.

Study on enhanced lymphatic tracing of isosulfan blue injection by influence of osmotic pressure on lymphatic exposure.

Science.gov (United States)

Ye, Tiantian; He, Rui; Wu, Yue; Shang, Lei; Wang, Shujun

2018-04-01

Isosulfan blue (IB) is being used as a lymphatic tracer has been approved by the FDA in 1981. This study aimed at improving lymphatic exposure of IB injection by osmotic pressure regulation to achieve step-by step lymphatic tracing. First, IB injection with appropriate osmotic pressure, stability, and suitable pH was prepared. Next, the lymphatic tracing ability of different osmotic pressure was studied to determine the blue-stained state of IB in three-level lymph nodes after subcutaneous administration. Furthermore, pharmacokinetics of lymphatic drainage, lymph node uptake, and plasma concentration was investigate to explore the improving law of the lymphatic tracing by osmotic pressure, and combined with tissue irritation to determine the optimal osmotic pressure. At last, the tissue distribution in mice of IB injection which had the property of optimal osmotic pressure was investigated. The results showed that increasing osmotic pressure could significantly reduce injection site retention and increase IB concentration of lymph node. The lymph nodes could be obviously blue-stained by IB injection which had 938 mmol/kg osmotic pressure and would not cause inflammatory reaction and blood exposure. The tissue distribution study suggested that IB injection which had 938 mmol/kg osmotic pressure was mainly distributed into gallbladder and duodenum that verified the reports that 90% IB was excreted through the feces through biliary excretion. In conclusion, this study provides the basic study to improve lymphatic exposure of IB injection by regulate the osmotic pressure and have the potential to be the helpful guidance for the elective lymph node dissection.

Noninvasive diagnosis of allograft vascular disease after heart transplantation

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Fernando Bacal

2001-01-01

Full Text Available OBJECTIVE: To determine the predictive values of noninvasive tests for the detection of allograft vascular disease. METHODS: We studied 39 patients with mean ages of 48±13 years and a follow-up period of 86±13 months. The diagnosis of allograft vascular disease was made by cine-coronary arteriography, and it was considered as positive if lesions existed that caused > or = 50% obstruction of the lumen. Patients underwent 24h Holter monitoring, thallium scintigraphy, a treadmill stress test, and dobutamine stress echocardiography. Sensitivity, specificity, and positive and negative predictive values were determined in percentages for each method, as compared with the cine-coronary arteriography results. RESULTS: Allograft vascular disease was found in 15 (38% patients. The Holter test showed 15.4% sensitivity, 95.5% specificity. For the treadmill stress test, sensitivity was 10%, specificity was 100%. When thallium scintigraphy was used, sensitivity was 40%, specificity 95.8%. On echocardiography with dobutamine, we found a 63.6% sensitivity, 91.3% specificity. When the dobutamine echocardiogram was associated with scintigraphy, sensitivity was 71.4%, specificity was 87%. CONCLUSION: In this group of patients, the combination of two noninvasive methods (dobutamine echocardiography and thallium scintigraphy may be a good alternative for the detection of allograft vascular disease in asymptomatic patients with normal ventricular function.

Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease

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Ya-Ru Wen

2018-01-01

Full Text Available Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease. The therapeutic effect of current pharmacotherapies is unsatisfactory, and some treatments cause severe side effects. The meningeal lymphatic vessels might be a new route for amyloid-β clearance. This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain. First, human lymphatic endothelial cells were treated with 100 ng/mL recombinant human vascular endothelial growth factor-C (rhVEGF-C protein. Light microscopy verified that rhVEGF-C, a specific ligand for vascular endothelial growth factor receptor-3 (VEGFR-3, significantly promoted tube formation of human lymphatic endothelial cells in vitro. In an in vivo study, 200 μg/mL rhVEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice, once every 2 days, four times in total. Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer's disease mice. One week after rhVEGF-C administration, enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain. The Morris water maze test demonstrated that spatial cognition was restored. These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice, suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.

Percutaneous Sclerotherapy of Congenital Slow-Flow Vascular Malformations of the Orbit

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Chiramel, George Koshy, E-mail: gkchiramel@gmail.com; Keshava, Shyamkumar Nidugala, E-mail: aparna-shyam@yahoo.com; Moses, Vinu, E-mail: vinu@cmcvellore.ac.in; Mammen, Suraj, E-mail: surajmammen77@gmail.com [Christian Medical College, Department of Radiology (India); David, Sarada, E-mail: saradadavid@gmail.com [Christian Medical College, Department of Ophthalmology (India); Sen, Sudipta, E-mail: paedsur@cmcvellore.ac.in [Christian Medical College, Department of Pediatric Surgery (India)

2015-04-15

PurposeThis manuscript describes the clinical features, imaging findings, treatment details, and short-term outcomes of a series of congenital slow-flow vascular malformations.MethodsThis was a prospective study of congenital slow-flow vascular malformations involving the orbital region treated at a single institution with percutaneous sclerotherapy.ResultsTen patients presented during the study period, comprising eight venous malformations, one lymphatic malformation, and one veno-lymphatic malformation. Nine patients underwent percutaneous sclerotherapy under digital subtraction angiography guidance, of which three developed marked rise in intraocular pressure requiring lateral canthotomy. The treatments were performed in the presence of an ophthalmologist who measured the intraorbital pressure during and after the procedure. On follow-up, some of the patients required repeat sessions of sclerotherapy. All patients had improvement of symptoms on follow up after the procedure.ConclusionCongenital slow-flow vascular malformations of the orbital region are rare lesions that should be treated using a multidisciplinary approach. Monitoring of the intraorbital pressure is required both during and after the procedure to decide about the need for lateral canthotomy to reduce the transiently increased intraorbital pressure.

Percutaneous Sclerotherapy of Congenital Slow-Flow Vascular Malformations of the Orbit

International Nuclear Information System (INIS)

Chiramel, George Koshy; Keshava, Shyamkumar Nidugala; Moses, Vinu; Mammen, Suraj; David, Sarada; Sen, Sudipta

2015-01-01

PurposeThis manuscript describes the clinical features, imaging findings, treatment details, and short-term outcomes of a series of congenital slow-flow vascular malformations.MethodsThis was a prospective study of congenital slow-flow vascular malformations involving the orbital region treated at a single institution with percutaneous sclerotherapy.ResultsTen patients presented during the study period, comprising eight venous malformations, one lymphatic malformation, and one veno-lymphatic malformation. Nine patients underwent percutaneous sclerotherapy under digital subtraction angiography guidance, of which three developed marked rise in intraocular pressure requiring lateral canthotomy. The treatments were performed in the presence of an ophthalmologist who measured the intraorbital pressure during and after the procedure. On follow-up, some of the patients required repeat sessions of sclerotherapy. All patients had improvement of symptoms on follow up after the procedure.ConclusionCongenital slow-flow vascular malformations of the orbital region are rare lesions that should be treated using a multidisciplinary approach. Monitoring of the intraorbital pressure is required both during and after the procedure to decide about the need for lateral canthotomy to reduce the transiently increased intraorbital pressure

Pleural function and lymphatics.

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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.

Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.

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Targher, Giovanni; Lonardo, Amedeo; Byrne, Christopher D

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.

Early Detection System of Vascular Disease and Its Application Prospect

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Huan Liu

2016-01-01

Full Text Available Markers of imaging, structure, and function reflecting vascular damage, integrating a long time accumulation effect of traditional and unrecognized cardiovascular risk factors, can be regarded as surrogate endpoints of target organ damage before the occurrence of clinical events. Prevention of cardiovascular disease requires risk stratification and treatment of traditional risk factors, such as smoking, hypertension, hyperlipidemia, and diabetes. However, traditional risk stratification is not sufficient to provide accurate assessment of future cardiovascular events. Therefore, vascular injury related parameters obtained by ultrasound or other noninvasive devices, as a surrogate parameter of subclinical cardiovascular disease, can improve cardiovascular risk assessment and optimize the preventive treatment strategy. Thus, we will summarize the research progress and clinical application of early assessment technology of vascular diseases in the present review.

The role of immunohistochemistry in the detection of vascular invasion in specimens of endoscopic submucosal dissection

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Nayze Lucena Sangreman Aldeman

2013-08-01

Full Text Available INTRODUCTION: Endoscopic submucosal dissection (ESD of early neoplasias of the gastrointestinal tract (GIT has been increasingly applied as an alternative to invasive surgical procedures, with the aim to preserve the patient's organ and quality of life, although it does not allow the histopathological analysis of lymph nodes. Previous studies demonstrated that the presence of neoplastic emboli in lymphatic (lymphatic vascular invasion [LVI] or blood vessels (blood vascular invasion [BVI] is considered a positive predictive factor for the occurrence of lymph node metastasis. The assessment of vascular invasion carried out only by routine hematoxylin and eosin staining (HE may yield both falsepositive and false-negative results. D2-40 is a specific monoclonal antibody to the lymphatic endothelium. Thus, it is useful for identifying LVI and distinguishing if tumor embolization is found in blood or lymphatic vessels. OBJECTIVE: To determine the role of immunohistochemistry (IHC in the assessment of ESD specimens by comparing the detection of LVI and BVI by HE and IHC with D2-40 and CD34 immunolabeling. METHOD: We conducted the IHC study using D2-40 and CD34 markers (pan-endothelial in 30 cases of ESD with histological diagnosis of carcinoma in order to assess the presence of LVI and BVI. RESULTS: The detection of LVI was more prevalent than BVI. Three out of six cases with LVI were false-positive by HE and six were false-negative by IHC. Regarding BVI, five cases were identified and one was false-negative by IHC. CONCLUSION: Our results indicated that the histopathological analysis of ESD specimens by exclusively routine HE staining does not allow proper evaluation of BVI or LVI.

Linking vascular disorders and Alzheimer’s disease: Potential involvement of BACE1

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Cole, Sarah L.; Vassar, Robert

2012-01-01

The etiology of Alzheimer’s disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation. PMID:18289733

Increased Vascular Disease Mortality Risk in Prediabetic Korean Adults Is Mainly Attributable to Ischemic Stroke.

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Kim, Nam Hoon; Kwon, Tae Yeon; Yu, Sungwook; Kim, Nan Hee; Choi, Kyung Mook; Baik, Sei Hyun; Park, Yousung; Kim, Sin Gon

2017-04-01

Prediabetes is a known risk factor for vascular diseases; however, its differential contribution to mortality risk from various vascular disease subtypes is not known. The subjects of the National Health Insurance Service in Korea (2002-2013) nationwide cohort were stratified into normal glucose tolerance (fasting glucose mortality risk for vascular disease and its subtypes-ischemic heart disease, ischemic stroke, and hemorrhagic stroke. When adjusted for age, sex, and body mass index, IFG stage 2, but not stage 1, was associated with significantly higher all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.18-1.34) and vascular disease mortality (HR, 1.27; 95% CI, 1.08-1.49) compared with normal glucose tolerance. Among the vascular disease subtypes, mortality from ischemic stroke was significantly higher (HR, 1.60; 95% CI, 1.18-2.18) in subjects with IFG stage 2 but not from ischemic heart disease and hemorrhagic stroke. The ischemic stroke mortality associated with IFG stage 2 remained significantly high when adjusted other modifiable vascular disease risk factors (HR, 1.51; 95% CI: 1.10-2.09) and medical treatments (HR, 1.75; 95% CI, 1.19-2.57). Higher IFG degree (fasting glucose, 110-125 mg/dL) was associated with increased all-cause and vascular disease mortality. The increased vascular disease mortality in IFG stage 2 was attributable to ischemic stroke, but not ischemic heart disease or hemorrhagic stroke in Korean adults. © 2017 American Heart Association, Inc.

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

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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.

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

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Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane

2015-01-01

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

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Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2015-07-01

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

Inapparent pulmonary vascular disease in an ex-heroin user

International Nuclear Information System (INIS)

Antonelli Incalzi, R.; Ludovico Maini, C.; Giuliano Bonetti, M.; Campioni, P.; Pistelli, R.; Fuso, L.

1986-01-01

A severe pulmonary vascular derangement, usually reported in drug addicts, was diagnosed in a 28-year-old asymptomatic ex-heroin user by means of fortuitously performed pulmonary perfusion imaging. Neither physical findings nor pulmonary function tests, aroused suspicion of the diagnosis. A search for asymptomatic pulmonary vascular disease probably should be undertaken in drug addicts

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

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Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

2016-04-04

The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

Diagnostic value of vascular endothelial growth factor and interleukin-17 in association with molecular diagnosis of Wuchereria bancrofti infection

OpenAIRE

Dalia Abdelhamid Omran; Mayssa Mohamed Zaki; Salwa Fayez Hasan; Hend Ibrahim Shousha

2015-01-01

Objective: To explore effective diagnosis of Wuchereria bancrofti through DNA-based techniques followed by assessment of vascular endothelial growth factor concentration (VEGF-C) and interleukin 17 (IL-17) as indicators for lymphatic endothelial cell activation, proliferation and massive tissue reaction that may be a good indicator for ongoing lymphatic filariasis. Methods: Blood samples were collected from 38 patients: 23 males (60.5%) and 15 females (39.5%) with filariasis...

Comparative and Developmental Anatomy of Cardiac Lymphatics

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A. Ratajska

2014-01-01

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

Intrathoracic manifestations of collagen vascular diseases on high-resolution chest computed tomography

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Silva, C. Isabela S. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital]. E-mail: isabela.silva@vch.ca; Mueller, Nestor L. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital. Dept. of Radiology

2008-05-15

Intrathoracic manifestations of collagen vascular diseases are very common. The frequency of intrathoracic manifestations and the patterns of abnormality are variable depending on the type of collagen vascular disease and may simultaneously involve one or more of the following: lung parenchyma, airways, pulmonary vessels, pericardium, and pleura. The most common pulmonary manifestations are diffuse interstitial pneumonia and pulmonary hypertension which together represent the main causes of morbidity and mortality of these patients. Pulmonary, airway and pleural involvement may also be secondary to the disease therapy, or result from bacterial pneumonia or opportunistic infection. In the present review, the authors summarize the main intrathoracic manifestations of collagen vascular diseases and the differential diagnosis on high-resolution chest computed tomography. (author)

Peripheral vascular disease in patients with coronary artery disease

International Nuclear Information System (INIS)

Bashir, E. A.; Aslam, N.

2001-01-01

Objective: The prevalence of peripheral vascular disease (PVD) in patients with coronary artery disease (CAD) has been investigated in many different ways. It depends on the diagnostic methods used and definition of atherosclerotic manifestations in the different vascular beds. This study was carried out to determine the prevalence of PVD in the lower limbs in group of patients with CAD. Design: This is a prospective observational study. Place and duration of study: The study was conducted at Combined Military Hospital/Armed Forces institute of Cardiology, Rawalpindi, over a period of one year (January 1998 to January 1999). Subjects and methods: A total number of 200 patient (171 male and 29 females) aged 55-77 years with CAD. Diagnosed by coronary angiography were included in the study. In all patients blood pressure was recorded in both arms by sphygmomanometer and ankle systolic pressure by Doppler ultrasound. Ankle branchial index was calculated. Demographic data were obtained from the patient's hospital files. Results: The prevalence of PVD was 22.5% in patients with CAD in agreement with the results of most previous investigation. There was tendency towards increasing prevalence of PVD with more advanced CAD. Thirty patients (27%) showed evidence of triple vessel disease as compared to 13 patient (18%) with double vessel and 2 patients (1%) with single vessel disease. Conclusion: A non-invasive investigation of peripheral arterial circulation should be included early in the clinical consideration of patients with chest pain or similar symptoms suggesting coronary artery disease. Ankle systolic pressure appears to be simple and cheap technique for evaluation of results. (author)

A series of parapharyngeal glial heterotopia mimicking lymphatic malformation.

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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.

Dramatic Vascular Course of Behcet's Disease

International Nuclear Information System (INIS)

Elsharawy, Mohamed A.; Hassan, Khairi A.; Al-Awami, Majed; Al-Mulhim, Fatma A.

2004-01-01

Vascular involvement in Behcet's disease is rare (approximately 14% venous and 1.6% arterial), serious and recurrent. We report a case of Behcet's disease with deep venous thrombosis and right iliac pseudoaneurysm which was repaired with polytetrafluoroethylene (PTFE) graft. The patient received warfarin, aspirin, clopidogrel, immunosupressive and corticosteroids. Two months later the patient developed manifestations of superior vena cava thrombosis and the graft was blocked. Three months later, ischemia of the right foot deteriorated and left femoral artery crossover (PTFE) graft was performed. (author)

Lamb congenital lymphatic malformation - a case report

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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.

Elevated circulating homocyst(e)ine levels in placental vascular disease and associated pre-eclampsia.

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Wang, J; Trudinger, B J; Duarte, N; Wilcken, D E; Wang, X L

2000-07-01

We examined the hypothesis that hyperhomocyst(e)inaemia in the maternal or fetal circulation is associated with placental vascular disease with either the maternal syndrome of pre-eclampsia and/or fetal syndrome of growth restriction. Maternal plasma homocyst(e)ine levels were significantly higher in pregnancies complicated by pre-eclampsia, pregnancies with evidence of umbilical placental vascular disease, and pregnancies with both complications compared with the normal pregnancy group. In the fetal circulation mean plasma homocyst(e)ine concentration was significantly higher in the pre-eclampsia group compared with the normal group. The results suggest that hyperhomocyst(e)inaemia may be a risk marker for placental vascular disease and maternal pre-eclampsia. The elevated fetal plasma homocyst(e)ine concentrations, found only in the group of pregnancies with pre-eclampsia in the absence of umbilical placental vascular disease, may be due to an effect of placental vascular disease on homocyst(e)ine transfer from the maternal to fetal circulation.

Usefulness of Diffusion Tensor Imaging of White Matter in Alzheimer Disease and Vascular Dementia

International Nuclear Information System (INIS)

Sugihara, S.; Kinoshita, T.; Matsusue, E.; Fujii, S.; Ogawa, T.

2004-01-01

Purpose: To evaluate the usefulness of diffusion tensor imaging in detecting the water diffusivity caused by neuro pathological change in Alzheimer disease and vascular dementia. Material and Methods: Twenty patients with Alzheimer disease, 20 with vascular dementia, and 10 control subjects were examined. Diffusion tensor imaging applied diffusion gradient encoding in six non-collinear directions. Fractional anisotropy values were compared in the genu and splenium of the corpus callosum, and anterior and posterior white matter among the three groups. Results: In the patients with Alzheimer disease, fractional anisotropy values of the posterior white matter were significantly lower than those of controls. In patients with vascular dementia, fractional anisotropy values of the anterior white matter tended to be lower than those of the posterior white matter (P=0.07). Conclusion: Diffusion tensor imaging reflects the neuro pathological changes in the white matter, and may be useful in the diagnosis of Alzheimer disease and vascular dementia. Keywords: Alzheimer disease, .; diffusion tensor imaging, .; vascular dementia

Shared constitutional risks for maternal vascular-related pregnancy complications and future cardiovascular disease

NARCIS (Netherlands)

A.L. Berends (Anne); C.J.M. de Groot (Christianne); E.J.G. Sijbrands (Eric); M.P.S. Sie (Mark); S.H. Benneheij (Sofie); R. Pal (Richard); R. Heydanus (Rogier); B.A. Oostra (Ben); P. Tikka-Kleemola (Päivi); R.P.M. Steegers-Theunissen (Régine)

2008-01-01

textabstractMaternal predisposition to vascular and metabolic disease may underlie both vascular-related pregnancy complications, such as preeclampsia and intrauterine growth restriction, as well as future maternal cardiovascular disease. We aimed to substantiate this hypothesis with biochemical and

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

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Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

2013-01-01

Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

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Rodolfo Mastropasqua

2015-01-01

Full Text Available Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA. Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA and indocyanine green angiography (ICGA with Spectralis HRA + OCT (Heidelberg Engineering GmbH were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes, age-related macular degeneration related (2, branch retinal vein occlusion (BRVO (2, and branch retinal artery occlusion (BRAO (1. OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics.

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Louveau, Antoine; Plog, Benjamin A; Antila, Salli; Alitalo, Kari; Nedergaard, Maiken; Kipnis, Jonathan

2017-09-01

Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.

Clinicopathological correlation of psychosis and brain vascular changes in Alzheimer's disease.

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Ting, Simon Kang Seng; Hao, Ying; Chia, Pei Shi; Tan, Eng-King; Hameed, Shahul

2016-02-12

Psychosis is common in Alzheimer's disease (AD). However, studies on neuropathology in vascular etiology contributing to psychosis in AD is lacking to date. The aim of this study was to investigate neuropathological vascular related changes in Alzheimer's disease with psychosis. Data of patients with AD from the National Alzheimer's Coordinating Center between 2005 to September 2013 was accessed and reviewed. Presence of psychosis was determined based on Neuropsychiatric Inventory Questionnaire taken from the last visit within one year prior to death, and patients were divided into psychosis positive and negative group. Comparison of clinical details and neuropathological vascular changes between the groups was performed using Wilcoxon rank sum test and Chi-square/ Fisher's exact test. Significant variables were further included in a multivariate logistic model. Overall, 145 patients was included. Of these, 50 patients were psychosis positive. Presence of one or more cortical microinfarcts and moderate to severe arteriosclerosis was found to be positively associated with psychosis. Our results suggest vascular changes correlate with psychosis in Alzheimer's disease.

Lymphatic albumin clearance from psoriatic skin

International Nuclear Information System (INIS)

Staberg, B.; Klemp, P.; Aasted, M.; Worm, A.M.; Lund, P.

1983-01-01

In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with 125 I or 131 I was injected intradermally in symmetrically located involved and uninvolved skin. The activity of the depots was followed by external detection, and the arrival of labelled albumin in plasma was monitored. In involved psoriatic skin the local mean half-time (T1/2) for tracer disappearance was 20.8 +/- 8.2 (S.D.) hr and in clinically normal skin, 29.1 +/- 9.6 (S.D.) hr. The difference was significant (p less than 0.002). Accordingly, the tracer from involved skin reached higher plasma levels than the tracer from uninvolved skin. However, under slight lymphatic stasis the appearance rate of radiolabelled albumin in plasma from both tissues was minimal during 1 to 2 hours after the injection, indicating that a local direct transvascular drainage of plasma albumin from the interstitium of diseased and normal skin was negligible. We conclude that the previously demonstrated increased extravasation of plasma proteins in involved psoriatic skin is compensated by an increased lymphatic drainage of plasma proteins, and not by an increased local transvascular return

HRCT of the lung in collagen vascular diseases

International Nuclear Information System (INIS)

Diederich, S.; Roos, N.; Schmitz-Linneweber, B.; Gaubitz, M.; Peters, P.E.

1996-01-01

Collagen vascular diseases, representing systemic soft tissue disorders, may cause a broad spectrum of pathologic changes of the respiratory tract. The type and extent of manifestations can vary considerably among individuals and entities. This survey describes the chest radiographic and, in particular, high-resolution computed tomographic and, in particular, high-resolution computed tomographic (HRCT) findings of individual lesions of the respiratory tract. It includes fibrosing alveolitis (alveolitis, interstitial pneumonia, pulmonary fibrosis) and bronchial (bronchitis/bronchiolitis, bronchiectasis), pleural and vascular manifestations, as well as lymphadenopathy and abnormalities related to therapy. We present typical patterns of changes in progressive systemic sclerosis (PSS, scleroderma), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD, Sharp syndrome), Sjoegren syndrome, overlap syndrome and rheumatoid arthritis (RA). Furthermore, we describe findings which are specific for individual entities such as esophageal involvement in PSS, acute pneumonitis and pulmonary hemorrhage in SLE, lymphoproliferative disease in Sjoegren syndrome and necrobiotic nodules in RA. (orig.) [de

Craniofacial CT findings of Gorham-Stout disease and generalized lymphatic anomaly

Energy Technology Data Exchange (ETDEWEB)

Kato, Hiroki; Matsuo, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Ozeki, Michio; Fukao, Toshiyuki [Gifu University School of Medicine, Department of Pediatrics, Gifu (Japan)

2016-08-15

The present study aimed to assess the craniofacial CT imaging features for differentiating between Gorham-Stout disease (GSD) and generalized lymphatic anomaly (GLA). Seven patients with GSD and four patients with GLA were included in this study. All patients underwent CT examinations that encompassed the craniofacial bones. The presence, distribution, and type of craniofacial osteolysis were assessed. The clinical symptoms that were associated with craniofacial osteolysis were also reviewed. Craniofacial osteolysis including cranial osteolysis was seen in four of seven (57 %) patients with GSD and in three of four (75 %) patients with GLA. Facial osteolysis was seen in two (29 %) patients with GSD, but this was not observed in patients with GLA. Among patients with craniofacial osteolysis, those with GSD showed diffuse involvement, whereas those with GLA showed multifocal involvement. The craniofacial osteolysis of GSD could be classified into three patterns: medullary involvement, thinning bone, and disappearing bone. The clinical symptoms of craniofacial osteolysis were observed in all patients with GSD but were not present in patients with GLA. Craniofacial involvement was observed in both groups. The craniofacial osteolysis of GSD showed diffuse involvement with clinical symptoms, whereas that of GLA showed multifocal involvement without clinical symptoms. (orig.)

Primary disorders of the lymphatic vessels--a unified concept.

Science.gov (United States)

Levine, C

1989-03-01

Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.

The effect of lymphatic valve morphology on fluid transport

Science.gov (United States)

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

2016-11-01

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

Pulmonary lymphatics and radiation

International Nuclear Information System (INIS)

Leeds, S.E.

1976-01-01

Knowledge of the anatomy and physiology of the respiratory system has been more difficult to acquire than that of other organ systems owing to the complexity of the respiratory function of the lungs and to the technical difficulties involved. This is especially true of the lymphatics of the lung and is illustrated by the fact that the first measurement of pulmonary lymph flow was in 1942 by Warren and Drinker. A review of the literature reveals that few experiments have been designed to study the pulmonary lymphatics per se in relation to the effects of external radiation or after the inhalation of radioactive particles. However, the documented involvement of hilar lymph nodes implies that the lung lymphatics have a role in transporting particles from the alveoli or malignant cells from the parenchyma. Information from clinical and experimental sources, though scattered, is fairly abundant and of value in assessing the role of the pulmonary lymphatics. Our method for collecting pulmonary lymph is presented. Studies on the pulmonary lymph flow in normal dogs and in dogs with experimental congestive heart failure are described. We irradiated (4000 to 5000 R) the medial one-third of both lungs of a series of dogs. The lymph flow of the lungs was measured immediately after the course of irradiation and after a period of about 5 months. Although lung biopsies showed characteristic radiation pneumonitis in many areas, alterations in the lung parenchyma were not quantitatively reflected in the pulmonary lymph flow either in the acute stage or after fibrosis had time to develop

Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease

DEFF Research Database (Denmark)

Sarwar, N; Gao, P; Seshasai, S R Kondapally

2010-01-01

BACKGROUND: Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. METHODS: We undertook a meta-analysis...... of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body......-mass index to calculate hazard ratios (HRs) for vascular disease. FINDINGS: Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8.49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2.00 (95% CI 1.83-2.19) for coronary heart...

Three-dimensional computer-assisted dissection of pancreatic lymphatic anatomy on human fetuses: a step toward automatic image alignment.

Science.gov (United States)

Bardol, T; Subsol, G; Perez, M-J; Genevieve, D; Lamouroux, A; Antoine, B; Captier, G; Prudhomme, M; Bertrand, M M

2018-05-01

Pancreatic cancer is the fourth cause of death by cancer worldwide. Lymph node (LN) involvement is known to be the main prognostic factor. However, lymphatic anatomy is complex and only partially characterized. The aim of the study was to study the pancreatic lymphatic system using computer-assisted anatomic dissection (CAAD) technique and also to update CAAD technique by automatizing slice alignment. We dissected three human fetuses aged from 18 to 34 WA. 5-µm serial sections of duodeno-pancreas and spleen blocks were stained (hematoxylin-eosin, hematoxylin of Mayer and Masson trichrome), scanned, aligned and modeled in three dimensions. We observed a rich, diffuse but not systematized lymphatic network in the peri-pancreatic region. There was an equal distribution of LNs between the cephalic and body-tail portions. The lymphatic vascularization appeared in continuity from the celiac trunk to the distal ends of its hepatic and splenic arterial branches parallel to the nerve ramifications of the celiac plexus. We also observed a continuity between the drainage of the pancreatic head and the para-aortic region posteriorly. In view of the wealth of peri-pancreatic LNs, the number of LNs to harvest could be increased to improve nodal staging and prognostic evaluation. Pancreatic anatomy as described does not seem to be compatible with the sentinel LN procedure in pancreatic surgery. Finally, we are now able to offer an alternative to manual alignment with a semi-automated alignment.

Comparative study of CT scan findings and intellectual function between Parkinson's disease and vascular Parkinsonism

International Nuclear Information System (INIS)

Indo, Toshikatsu

1986-01-01

Comparative study of CT scan findings and intellectual function between 64 cases with Parkinson's disease and 25 cases with vascular Parkinsonism was carried out. The rate of abnormality of CT scan findings, either ventricular dilatation or widening of sulci, in vascular Parkinsonism was strikingly high compared with Parkinson's disease. Patients could be divided into three groups according to the degree of overall abnormalities of CT scan findings (group A: markedly abnormal, group B: mildly abnormal, group C: normal). Incidences of group A were 9.4 % in Parkinson's disease and 52 % in vascular Parkinsonism, whereas those of group C were 56 % in the former and 28 % in the latter. All patients of group A were over 65 years of age in Parkinson's disease, but one-third of patients in group A were under 59 years of age in vascular Parkinsonism. Moreover, in vascular Parkinsonism, the level of disability was directly proportional to the abnormality of CT scan findings. The rate of predementia and dementia classified by Hasegawa's intelligence scale was 12.5 % in Parkinson's disease and 48 % in vascular Parkinsonism. No difference was found between the mean values of intelligence scale and background factors in Parkinson's disease. On the other hand, the mean value was significantly low in proportion to the poverty of L-dopa effect in vascular Parkinsonism. From these results, the abnormality of CT scan findings and intellectual impairment were probably related to the cerebral pathological process in vascular Parkinsonism, but these relationship was absent in Parkinson's disease. (author)

Comparative study of CT scan findings and intellectual function between Parkinson's disease and vascular Parkinsonism

Energy Technology Data Exchange (ETDEWEB)

Indo, Toshikatsu

1986-01-01

Comparative study of CT scan findings and intellectual function between 64 cases with Parkinson's disease and 25 cases with vascular Parkinsonism was carried out. The rate of abnormality of CT scan findings, either ventricular dilatation or widening of sulci, in vascular Parkinsonism was strikingly high compared with Parkinson's disease. Patients could be divided into three groups according to the degree of overall abnormalities of CT scan findings (group A: markedly abnormal, group B: mildly abnormal, group C: normal). Incidences of group A were 9.4 % in Parkinson's disease and 52 % in vascular Parkinsonism, whereas those of group C were 56 % in the former and 28 % in the latter. All patients of group A were over 65 years of age in Parkinson's disease, but one-third of patients in group A were under 59 years of age in vascular Parkinsonism. Moreover, in vascular Parkinsonism, the level of disability was directly proportional to the abnormality of CT scan findings. The rate of predementia and dementia classified by Hasegawa's intelligence scale was 12.5 % in Parkinson's disease and 48 % in vascular Parkinsonism. No difference was found between the mean values of intelligence scale and background factors in Parkinson's disease. On the other hand, the mean value was significantly low in proportion to the poverty of L-dopa effect in vascular Parkinsonism. From these results, the abnormality of CT scan findings and intellectual impairment were probably related to the cerebral pathological process in vascular Parkinsonism, but these relationship was absent in Parkinson's disease.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature.

Science.gov (United States)

Cabibi, Daniela; Pipitone, Giulia; Porcasi, Rossana; Ingrao, Sabrina; Benza, Ignazio; Porrello, Calogero; Cajozzo, Massimo; Giannone, Antonino Giulio

2017-08-15

Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood cells and containing Alcian blue positive material. The tumor showed positive immunostaining for Vimentin, CD31, CK7, D2-40, c-MYC, Ki67, focal positivity for PanCK, and negative immunostaining for Factor VIII, CD34, WT1, CK5/6, Calretinin, EMA, HBME-1, CEA, p63, EpCAM, Bcl-2, TTF1 and Thyroglobulin. CD99 showed a granular/paranuclear pattern of positivity. The histological and immunohistochemical features were consistent with "pleural angiosarcoma with lymphatic differentiation, epithelioid variant". Epithelioid angiosarcoma with lymphatic differentiation is very rare and aggressive. Moreover, the positivity for c-MYC suggests the relationship with radiometabolic therapy. To our knowledge, this is the first case of pleural c-MYC-positive angiosarcoma with lymphatic differentiation reported in the literature and the first one arisen after radiometabolic therapy for thyroid carcinoma.

Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

Science.gov (United States)

Feldman, Steven R; Huang, William W; Huynh, Tu T

2014-06-01

Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

IR imaging of blood circulation of patients with vascular disease

Science.gov (United States)

Wang, Hsin; Wade, Dwight R., Jr.; Kam, Jack

2004-04-01

We conducted a preliminary IR imaging study of blood circulation in patients with peripheral vascular diseases. Abnormal blood flow is common in older adults, especially those with elevated blood lipids, diabetes, hypertension, and a history of smoking. All of these conditions have a high prevalence in our population, often with more than one condition in the same individual. The differences in blood flow is revealed by temperature differences in areas of the extremities as well as other regions of the body. However, what is needed is an imaging technique that is relatively inexpensive and can reveal the blood flow in real time. The IR imaging can show detailed venous system and small tempearture changes associated with blood flow. Six patients with vascular diseases were tested in a clinic set up. Their legs and feet were imaged. We observed large temperature differences (cooling of more than 10° C) at the foot, especially toes. More valuable information were obtained from the temperature distribution maps. IR thermography is potentially a very valuable tool for medical application, especially for vascular diseases.

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

NARCIS (Netherlands)

Clarijs, Johannes Antonius Godefridus Marinus

2003-01-01

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

Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

Directory of Open Access Journals (Sweden)

Villegas VM

2014-05-01

Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

Science.gov (United States)

Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

2011-08-01

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

Lymphatic endothelial cells efferent to inflamed joints produce iNOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice.

Science.gov (United States)

Liang, Qianqian; Ju, Yawen; Chen, Yan; Wang, Wensheng; Li, Jinlong; Zhang, Li; Xu, Hao; Wood, Ronald W; Schwarz, Edward M; Boyce, Brendan F; Wang, Yongjun; Xing, Lianping

2016-03-12

In this study, we sought to determine the cellular source of inducible nitric oxide synthase (iNOS) induced in lymphatic endothelial cells (LECs) in response to tumor necrosis factor (TNF), the effects of iNOS on lymphatic smooth muscle cell (LSMC) function and on the development of arthritis in TNF-transgenic (TNF-Tg) mice, and whether iNOS inhibitors improve lymphatic function and reduce joint destruction in inflammatory erosive arthritis. We used quantitative polymerase chain reactions, immunohistochemistry, histology, and near-infrared imaging to examine (1) iNOS expression in podoplanin + LECs and lymphatic vessels from wild-type (WT) and TNF-Tg mice, (2) iNOS induction by TNF in WT LECs, (3) the effects of iNOS inhibitors on expression of functional muscle genes in LSMCs, and (4) the effects of iNOS inhibitors on lymphatic vessel contraction and drainage, as well as the severity of arthritis, in TNF-Tg mice. LECs from TNF-Tg mice had eight fold higher iNOS messenger RNA levels than WT cells, and iNOS expression was confirmed immunohistochemically in podoplanin + LECs in lymphatic vessels from inflamed joints. TNF (0.1 ng/ml) increased iNOS levels 40-fold in LECs. LSMCs cocultured with LECs pretreated with TNF had reduced expression of functional muscle genes. This reduction was prevented by ferulic acid, which blocked nitric oxide production. Local injection of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide into inflamed paws of TNF-Tg mice resulted in recovery of lymphatic vessel contractions and drainage. Treatment of TNF-Tg mice with ferulic acid reduced synovial inflammation as well as cartilage and bone erosion, and it also restored lymphatic contraction and drainage. iNOS is produced primarily by LECs in lymphatic vessel efferent from inflamed joints of TNF-Tg mice in response to TNF and inhibits LSMC contraction and lymph drainage. Ferulic acid represents a potential new therapy to restore lymphatic function and thus improve inflammatory

Imaging of the interaction of cancer cells and the lymphatic system.

Science.gov (United States)

Tran Cao, Hop S; McElroy, Michele; Kaushal, Sharmeela; Hoffman, Robert M; Bouvet, Michael

2011-09-10

A thorough understanding of the lymphatic system and its interaction with cancer cells is crucial to our ability to fight cancer metastasis. Efforts to study the lymphatic system had previously been limited by the inability to visualize the lymphatic system in vivo in real time. Fluorescence imaging can address these limitations and allow for visualization of lymphatic delivery and trafficking of cancer cells and potentially therapeutic agents as well. Here, we review recent articles in which antibody-fluorophore conjugates are used to label the lymphatic network and fluorescent proteins to label cancer cells in the evaluation of lymphatic delivery and imaging. Copyright © 2011 Elsevier B.V. All rights reserved.

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.

Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia.

Science.gov (United States)

Barker, Rachel; Ashby, Emma L; Wellington, Dannielle; Barrow, Vivienne M; Palmer, Jennifer C; Kehoe, Patrick G; Esiri, Margaret M; Love, Seth

2014-05-01

Little is known about the contributors and physiological responses to white matter hypoperfusion in the human brain. We previously showed the ratio of myelin-associated glycoprotein to proteolipid protein 1 in post-mortem human brain tissue correlates with the degree of ante-mortem ischaemia. In age-matched post-mortem cohorts of Alzheimer's disease (n = 49), vascular dementia (n = 17) and control brains (n = 33) from the South West Dementia Brain Bank (Bristol), we have now examined the relationship between the ratio of myelin-associated glycoprotein to proteolipid protein 1 and several other proteins involved in regulating white matter vascularity and blood flow. Across the three cohorts, white matter perfusion, indicated by the ratio of myelin-associated glycoprotein to proteolipid protein 1, correlated positively with the concentration of the vasoconstrictor, endothelin 1 (P = 0.0005), and negatively with the concentration of the pro-angiogenic protein, vascular endothelial growth factor (P = 0.0015). The activity of angiotensin-converting enzyme, which catalyses production of the vasoconstrictor angiotensin II was not altered. In samples of frontal white matter from an independent (Oxford, UK) cohort of post-mortem brains (n = 74), we confirmed the significant correlations between the ratio of myelin-associated glycoprotein to proteolipid protein 1 and both endothelin 1 and vascular endothelial growth factor. We also assessed microvessel density in the Bristol (UK) samples, by measurement of factor VIII-related antigen, which we showed to correlate with immunohistochemical measurements of vessel density, and found factor VIII-related antigen levels to correlate with the level of vascular endothelial growth factor (P = 0.0487), suggesting that upregulation of vascular endothelial growth factor tends to increase vessel density in the white matter. We propose that downregulation of endothelin 1 and upregulation of vascular endothelial growth factor in the context

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

Science.gov (United States)

Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

2013-04-01

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

Binswanger's disease: biomarkers in the inflammatory form of vascular cognitive impairment and dementia.

Science.gov (United States)

Rosenberg, Gary A

2018-03-01

Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the impact of vascular disease on Alzheimer's disease. VCID is a heterogeneous group of diseases for which there are no proven treatments. Biomarkers can be used to select more homogeneous populations. Small vessel disease is the most prevalent form of VCID and is the optimal form for treatment trials because there is a progressive course with characteristic pathological changes. Subcortical ischemic vascular disease of the Binswanger type (SIVD-BD) has a characteristic set of features that can be used both to identify patients and to follow treatment. SIVD-BD patients have clinical, neuropsychological, cerebrospinal fluid (CSF) and imaging features that can be used as biomarkers. No one feature is diagnostic, but a multimodal approach defines the SIVD-BD spectrum disorder. The most important features are large white matter lesions with axonal damage, blood-brain barrier disruption as shown by magnetic resonance imaging and CSF, and neuropsychological evidence of executive dysfunction. We have used these features to create a Binswanger Disease Scale and a probability of SIVD-BD, using a machine-learning algorithm. The patients discussed in this review are derived from published studies. Biomarkers not only aid in early diagnosis before the disease process has progressed too far for treatment, but also can indicate response to treatment. Refining the use of biomarkers will allow dementia treatment to enter the era of precision medicine. This article is part of the Special Issue "Vascular Dementia". © 2017 International Society for Neurochemistry.

N-acetylcysteine improves arterial vascular reactivity in patients with chronic kidney disease

DEFF Research Database (Denmark)

Wittstock, Antje; Burkert, Magdalena; Zidek, Walter

2009-01-01

Patients with stage 5 chronic kidney disease show increased cardiovascular morbidity and mortality that are partly related to impaired arterial vascular reactivity. We investigated whether intravenous administration of the antioxidant acetylcysteine improves arterial vascular reactivity in these ...

Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

Science.gov (United States)

Christianson, Dawn R; Dobroff, Andrey S; Proneth, Bettina; Zurita, Amado J; Salameh, Ahmad; Dondossola, Eleonora; Makino, Jun; Bologa, Cristian G; Smith, Tracey L; Yao, Virginia J; Calderone, Tiffany L; O'Connell, David J; Oprea, Tudor I; Kataoka, Kazunori; Cahill, Dolores J; Gershenwald, Jeffrey E; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2015-02-24

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis

International Nuclear Information System (INIS)

Shibuya, Masabumi; Claesson-Welsh, Lena

2006-01-01

The VEGF/VPF (vascular endothelial growth factor/vascular permeability factor) ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates. VEGF-A, the prototype VEGF ligand, binds and activates two tyrosine kinase receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). VEGFR1, which occurs in transmembrane and soluble forms, negatively regulates vasculogenesis and angiogenesis during early embryogenesis, but it also acts as a positive regulator of angiogenesis and inflammatory responses, playing a role in several human diseases such as rheumatoid arthritis and cancer. The soluble VEGFR1 is overexpressed in placenta in preeclampsia patients. VEGFR2 has critical functions in physiological and pathological angiogenesis through distinct signal transduction pathways regulating proliferation and migration of endothelial cells. VEGFR3, a receptor for the lymphatic growth factors VEGF-C and VEGF-D, but not for VEGF-A, regulates vascular and lymphatic endothelial cell function during embryogenesis. Loss-of-function variants of VEGFR3 have been identified in lymphedema. Formation of tumor lymphatics may be stimulated by tumor-produced VEGF-C, allowing increased spread of tumor metastases through the lymphatics. Mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases

Ample spectrum of vascular hepatic disease

International Nuclear Information System (INIS)

Camacho, Juan C; Marquez Adriana; Romero, Javier; Aguirre Diego

2010-01-01

Hepatic vascular diseases (HVD) are a broad spectrum of entities of low prevalence but with different clinical manifestations that may even lead to death. Its early detection and timely treatment may change the prognosis. Diagnostic imaging plays a key role and imaging findings may be typical. However, in most cases, radiologists must take into account a wide range of differential diagnosis. Computed tomography (CT) of the abdomen is one of the most useful tools for the diagnosis of HVD taking also into account the value of other imaging methods such as Doppler Ultrasound and Magnetic Resonance Imaging (MRI). HVD can be classified according to the compromised vascular structure and can be divided into venous, portal, arterial, sinusoidal and others disorders. The objective of this review is to describe the most common presentation HVD. The major imaging findings and differential diagnosis recognizing its correlation with the pathophysiological mechanisms.

Imaging findings and therapeutic alternatives for peripheral vascular malformations

International Nuclear Information System (INIS)

Monsignore, Lucas Moretti; Nakiri, Guilherme Seizem; Santos, Daniela dos; Abud, Thiago Giansante; Abud, Daniel Giansante

2010-01-01

Peripheral vascular malformations represent a spectrum of lesions that appear through the lifetime and can be found in the whole body. Such lesions are uncommon and are frequently confounded with infantile hemangioma, a common benign neoplastic lesion. In the presence of such lesions, the correlation between the clinical and radiological findings is extremely important to achieve a correct diagnosis, which will guide the best therapeutic approach. The most recent classifications for peripheral vascular malformations are based on the blood flow (low or high) and on the main vascular components (arterial, capillary, lymphatic or venous). Peripheral vascular malformations represent a diagnostic and therapeutic challenge, and complementary methods such as computed tomography, Doppler ultrasonography and magnetic resonance imaging, in association with clinical findings can provide information regarding blood flow characteristics and lesions extent. Arteriography and venography confirm the diagnosis, evaluate the lesions extent and guide the therapeutic decision making. Generally, low flow vascular malformations are percutaneously treated with sclerosing agents injection, while in high flow lesions the approach is endovascular, with permanent liquid or solid embolization agents. (author)

Community members' perceptions of mass drug administration for control of lymphatic filariasis in rural rural and urban Tanzania

DEFF Research Database (Denmark)

Kisoka, William J.; Tersbøl, Britt Pinkowski; Meyrowitsch, Dan Wolf

2016-01-01

Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as 'neglected diseases of poverty'. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general...

Comparison of three quality of life instruments in lymphatic filariasis: DLQI, WHODAS 2.0, and LFSQQ.

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Cristina Thomas

2014-02-01

Full Text Available BACKGROUND: The Global Program to Eliminate Lymphatic Filariasis aims to interrupt transmission of lymphatic filariasis and manage morbidity in people currently living with the disease. A component of morbidity management is improving health-related quality of life (HRQoL in patients. Measurement of HRQoL in current management programs is varied because of the lack of a standard HRQoL tool for use in the lymphatic filariasis population. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the psychometric properties of three health status measures were compared when used in a group of lymphatic filariasis patients and healthy controls. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0, the Dermatology Life Quality Index (DLQI, and the Lymphatic Filariasis Quality of Life Questionnaire (LFSQQ were administered to 36 stage II and stage III lymphatic filariasis subjects and 36 age and sex matched controls in Kerala, India. All three tools yielded missing value rates lower than 10%, suggesting high feasibility. Highest internal consistency was seen in the LFSQQ (α = 0.97. Discriminant validity analysis demonstrated that HRQoL was significantly lower in the LF group than in controls for the WHODAS 2.0, DLQI, and LFSQQ, but total HRQoL scores did not differ between stage II and stage III lymphedema subjects. The LFSQQ total score correlated most strongly with the WHODAS 2.0 (r = 0.91, p<0.001 and DLQI (r = 0.81, p<0.001. CONCLUSIONS/SIGNIFICANCE: The WHODAS 2.0, DLQI, and LFSQQ demonstrate acceptable feasibility, internal consistency, discriminate validity, and construct validity. Based on our psychometric analyses, the LFSQQ performs the best and is recommended for use in the lymphatic filariasis population.

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

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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.

Lymphatic vessel density and function in experimental bladder cancer

International Nuclear Information System (INIS)

Saban, Marcia R; Wu, Xue-Ru; Saban, Ricardo; Towner, Rheal; Smith, Nataliya; Abbott, Andrew; Neeman, Michal; Davis, Carole A; Simpson, Cindy; Maier, Julie; Mémet, Sylvie

2007-01-01

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. 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. 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 flow within the tumoral area. In addition, NIRF

Laryngeal spaces and lymphatics: current anatomic concepts

International Nuclear Information System (INIS)

Welsh, L.W.; Welsh, J.J.; Rizzo, T.A. Jr.

1983-01-01

This investigation evaluates the anatomic concepts of individual spaces or compartments within the larynx by isotope and dye diffusion. The authors identified continuity of spaces particularly within the submucosal planes and a relative isolation within the fixed structures resulting from the longitudinal pattern of fibroelastic tissues, muscle bands, and perichondrium. The historical data of anatomic resistance are refuted by the radioisotope patterns of dispersion and the histologic evidence of tissue permeability to the carbon particles. There is little clinical application of the compartment concept to the perimeter of growth and the configuration of extensive endolaryngeal cancers. The internal and extralaryngeal lymphatic network is presented and the regional associations are identified. The normal ipsilateral relationship is distorted by dispersion within the endolarynx supervening the anatomic midline. The effects of lymphatic obstruction caused by regional lymphadenectomy, tumor fixation, and irradiation-infection sequelae are illustrated; these result in widespread bilateral lymphatic nodal terminals. Finally, the evidence suggests that the internal network is modified by external interruption to accommodate an outflow system in continuity with the residual patent lymphatic channels

Dipeptidyl peptidase-4 inhibitor gemigliptin protects against vascular calcification in an experimental chronic kidney disease and vascular smooth muscle cells.

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Soon-Youn Choi

Full Text Available Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats. In cultured vascular smooth muscle cells, phosphate-induced increase in calcium content was reduced by gemigliptin. Gemigliptin reduced phosphate-induced PiT-1 mRNA expression, reactive oxygen species generation, and NADPH oxidase mRNA expression (p22phox and NOX4. The reduction of oxidative stress by gemigliptin was associated with the downregulation of phospho-PI3K/AKT expression. High phosphate increased the expression of frizzled-3 (FDZ3 and decreased the expression of dickkopf-related protein-1 (DKK-1 in the Wnt pathway. These changes were attenuated by gemigliptin treatment. Gemigliptin restored the decreased expression of vascular smooth muscle cells markers (α-SMA and SM22α and increased expression of osteogenic makers (CBFA1, OSX, E11, and SOST induced by phosphate. In conclusion, gemigliptin attenuated vascular calcification and osteogenic trans-differentiation in vascular smooth muscle cells via multiple steps including downregulation of PiT-1 expression and suppression of reactive oxygen species generation, phospho-PI3K/AKT, and the Wnt signaling pathway.

Impaired vascular reactivity in patients with chronic kidney disease

DEFF Research Database (Denmark)

Tetzner, Fabian; Scholze, Alexandra; Wittstock, Antje

2008-01-01

Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics....

Temperature-dependent modulation of regional lymphatic contraction frequency and flow.

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

2017-11-01

Lymph drainage and propulsion are sustained by an extrinsic mechanism, based on mechanical forces acting from the surrounding tissues against the wall of lymphatic vessels, and by an intrinsic mechanism attributable to active spontaneous contractions of the lymphatic vessel muscle. Despite being heterogeneous, the mechanisms underlying the generation of spontaneous contractions share a common biochemical nature and are thus modulated by temperature. In this study, we challenged excised tissues from rat diaphragm and hindpaw, endowed with spontaneously contracting lymphatic vessels, to temperatures from 24°C (hindpaw) or 33°C (diaphragmatic vessels) to 40°C while measuring lymphatic contraction frequency ( f c ) and amplitude. Both vessel populations displayed a sigmoidal relationship between f c and temperature, each centered around the average temperature of surrounding tissue (36.7 diaphragmatic and 32.1 hindpaw lymphatics). Although the slope factor of the sigmoidal fit to the f c change of hindpaw vessels was 2.3°C·cycles -1 ·min -1 , a value within the normal range displayed by simple biochemical reactions, the slope factor of the diaphragmatic lymphatics was 0.62°C·cycles -1 ·min -1 , suggesting the added involvement of temperature-sensing mechanisms. Lymph flow calculated as a function of temperature confirmed the relationship observed on f c data alone and showed that none of the two lymphatic vessel populations would be able to adapt to the optimal working temperature of the other tissue district. This poses a novel question whether lymphatic vessels might not adapt their function to accommodate the change if exposed to a surrounding temperature, which is different from their normal condition. NEW & NOTEWORTHY This study demonstrates to what extent lymphatic vessel intrinsic contractility and lymph flow are modulated by temperature and that this modulation is dependent on the body district that the vessels belong to, suggesting a possible

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.

Quantum dots trace lymphatic drainage from the mouse eye

International Nuclear Information System (INIS)

Tam, Alex L C; Gupta, Neeru; Zhang Zhexue; Yuecel, Yeni H

2011-01-01

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.

The Use of N-Terminal Pro-Brain Natriuretic Peptide to Evaluate Vascular Disease in Elderly Patients with Mental Illness

OpenAIRE

Nilsson, Karin; Gustafson, Lars; Hultberg, Björn

2012-01-01

Background: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is regarded as a sensitive marker of cardiovascular disease. Vascular disease plays an important role in cognitive impairment. Method: In 447 elderly patients with mental illness, serum NT-proBNP level and the presence or absence of vascular disease according to the medical record were used to categorize patients in different subgroups of vascular disease. Results and Conclusion: Patients with vascular disease and elevated...

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 skeletal muscle contraction (Dmc) decreased to 61.3 ± 1.4% of the precontraction value [resting diameter (Drest)]; however, if injection was 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.

Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease

NARCIS (Netherlands)

Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A.; Kappelle, L. Jaap; de Borst, Gert Jan; Cramer, Maarten J.; Visseren, Frank L.J.; Aboyans, Victor; Westerink, Jan

2017-01-01

Background Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and

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

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 ...

Distinguishing between vascular dementia and Alzheimer's disease by means of the WAIS : A meta-analysis

NARCIS (Netherlands)

Scherder, Erik J. A.; Oosterman, J

2006-01-01

This study was intended to, meta-analytically, review whether the subtests of the Wechsler Adult Intelligence Scale are useful in differentiating between vascular dementia and Alzheimer's disease. We expected the Alzheimer's disease group to outperform the vascular dementia group on those subtests

Distinguishing between vascular dementia and Alzheimer's disease by means of the WAIS: A meta-analysis

NARCIS (Netherlands)

Scherder, E.J A; Oosterman, J

2006-01-01

This study was intended to, meta-analytically, review whether the subtests of the Wechsler Adult Intelligence Scale are useful in differentiating between vascular dementia and Alzheimer's disease. We expected the Alzheimer's disease group to outperform the vascular dementia group on those subtests

Distinguishing between vascular dementia and alzheimer's disease by means of the WAIS: a meta-analysis.

NARCIS (Netherlands)

Oosterman, J.M.; Scherder, E.J.A.

2006-01-01

This study was intended to, meta-analytically, review whether the subtests of the Wechsler Adult Intelligence Scale are useful in differentiating between vascular dementia and Alzheimer's disease. We expected the Alzheimer's disease group to outperform the vascular dementia group on those subtests

C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma.

Science.gov (United States)

Kawamata, Futoshi; Homma, Shigenori; Kamachi, Hirofumi; Einama, Takahiro; Kato, Yasutaka; Tsuda, Masumi; Tanaka, Shinya; Maeda, Masahiro; Kajino, Kazunori; Hino, Okio; Takahashi, Norihiko; Kamiyama, Toshiya; Nishihara, Hiroshi; Taketomi, Akinobu; Todo, Satoru

2014-01-01

Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay. Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr). Immunohistochemically, "luminal membrane positive" of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients' prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), "luminal membrane positive" of mesothelin significantly correlated with unfavorable patients' outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P ERC/mesothelin associated with lymphatic invasion of cancer in vitro.

Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

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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.

Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods

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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.

The lymphatic mechanisms of brain cleaning: application of optical coherence tomography and fluorescence microscopy

Science.gov (United States)

Glushkovskaya-Semyachkina, O.; Abdurashitov, A.; Fedosov, I.; Namykin, A.; Pavlov, A.; Shirokov, A.; Shushunova, N.; Sindeeva, O.; Khorovodov, A.; Ulanova, M.; Sagatova, V.; Agranovich, I.; Bodrova, A.; Kurths, J.

2018-04-01

Here we studied the role of cerebral lymphatic system in the brain clearing using intraparenchymal injection of Evans Blue and gold nanorods assessed by optical coherent tomography and fluorescence microscopy. Our data clearly show that the cerebral lymphatic system plays an important role in the brain cleaning via meningeal lymphatic vessels but not cerebral veins. Meningeal lymphatic vessels transport fluid from the brain into the deep cervical node, which is the first anatomical "station" for lymph outflow from the brain. The lymphatic processes underlying brain clearing are more slowly vs. peripheral lymphatics. These results shed light on the lymphatic mechanisms responsible for brain clearing as well as interaction between the intra- and extracranial lymphatic compartment.

Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing

Science.gov (United States)

Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Bragin, Denis; Bragina, Olga; Shushunova, Nataliya; Maslyakova, Galina; Navolokin, Nikita; Bucharskaya, Alla; Tuchin, Valery; Kurths, Juergen; Shirokov, Alexander

2017-12-01

The meningeal lymphatic vessels were discovered 2 years ago as the drainage system involved in the mechanisms underlying the clearance of waste products from the brain. The blood-brain barrier (BBB) is a gatekeeper that strongly controls the movement of different molecules from the blood into the brain. We know the scenarios during the opening of the BBB, but there is extremely limited information on how the brain clears the substances that cross the BBB. Here, using the model of sound-induced opening of the BBB, we clearly show how the brain clears dextran after it crosses the BBB via the meningeal lymphatic vessels. We first demonstrate successful application of optical coherence tomography (OCT) for imaging of the lymphatic vessels in the meninges after opening of the BBB, which might be a new useful strategy for noninvasive analysis of lymphatic drainage in daily clinical practice. Also, we give information about the depth and size of the meningeal lymphatic vessels in mice. These new fundamental data with the applied focus on the OCT shed light on the mechanisms of brain clearance and the role of lymphatic drainage in these processes that could serve as an informative platform for a development of therapy and diagnostics of diseases associated with injuries of the BBB such as stroke, brain trauma, glioma, depression, or Alzheimer disease.

Skin autofluorescence associates with vascular calcification in chronic kidney disease.

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Wang, Angela Yee-Moon; Wong, Chun-Kwok; Yau, Yat-Yin; Wong, Sharon; Chan, Iris Hiu-Shuen; Lam, Christopher Wai-Kei

2014-08-01

This study aims to evaluate the relationship between tissue advanced glycation end products, as reflected by skin autofluorescence, and vascular calcification in chronic kidney disease. Three hundred patients with stage 3 to 5 chronic kidney disease underwent multislice computed tomography to estimate total coronary artery calcium score (CACS) and had tissue advanced glycation end product assessed using a skin autofluorescence reader. Intact parathyroid hormone (Pskin autofluorescence after age (Pskin autofluorescence was associated with a 7.43-fold (95% confidence intervals, 3.59-15.37; PSkin autofluorescence retained significance in predicting CACS ≥400 (odds ratio, 3.63; 95% confidence intervals, 1.44-9.18; P=0.006) when adjusting for age, sex, serum calcium, phosphate, albumin, C-reactive protein, lipids, blood pressure, estimated glomerular filtration rate, and intact parathyroid hormone but marginally lost significance when additionally adjusting for diabetes mellitus (odds ratio, 2.23; 95% confidence intervals, 0.81-6.14; P=0.1). Combination of diabetes mellitus and higher intact parathyroid hormone was associated with greater skin autofluorescence and CACS versus those without diabetes mellitus and having lower intact parathyroid hormone. Tissue advanced glycation end product, as reflected by skin autofluorescence, showed a significant novel association with vascular calcification in chronic kidney disease. These data suggest that increased tissue advanced glycation end product may contribute to vascular calcification in chronic kidney disease and diabetes mellitus and warrant further experimental investigation. © 2014 American Heart Association, Inc.

Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

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Pappa, Theodora; Alevizaki, Maria

2012-08-01

Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

CARDIO-VASCULAR RISK FACTORS IN ELDERLY PATIENTS WITH DISEASES OF THE STOMATOGNATHIC SYSTEM

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Botez C

2011-09-01

Full Text Available The association between dental and cardio-vascular diseases is essential as both are highly prevalent. Finding a possible causal relation between cardiovascular disease and chronic periodontal pathology, known to cause tooth loss, is therefore essential. The existence of some risk factors, such as smoking, bacterial infections, malnutrition and nutritional deficiencies, may explain the associations observed between cardio-vascular and oral pathologies. In the case of dental diseases, acceleration of atherosclerosis is supported by the role played by infections. The study – performed between 2008-2009 – analyzed 45 cases, selected from the patients hospitalized in the Medical Clinics of the Military Hospital of Ia[i. The patients included in the study suffered from arterial hypertension (HTA, cardiac insufficiency, ischemic cardiopathy, pectoral angina and subacute infectious endocarditis. All were subjected to a stomatological examination, for establishing their dental hygiene, the stomatological diseases they had had and the treatments performed. There are several ways in which infections of the oral cavity lead to cardiovascular disease. These include: transitory bacteriemia; inflammation and vascular lesions; diet and smoking.

The Use of N-Terminal Pro-Brain Natriuretic Peptide to Evaluate Vascular Disease in Elderly Patients with Mental Illness

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Karin Nilsson

2012-02-01

Full Text Available Background: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP is regarded as a sensitive marker of cardiovascular disease. Vascular disease plays an important role in cognitive impairment. Method: In 447 elderly patients with mental illness, serum NT-proBNP level and the presence or absence of vascular disease according to the medical record were used to categorize patients in different subgroups of vascular disease. Results and Conclusion: Patients with vascular disease and elevated serum NT-proBNP level had a lower cognition level, shorter survival time, lower renal function and a higher percentage of pathological brain imaging than patients with vascular disease and normal NT-proBNP level. Thus, elevated serum NT-proBNP level might be helpful to detect patients who have a more severe cardiovascular disease.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Effect of VEGF-C siRNA and endostatin on ring formation and proliferation of esophageal squamous cell carcinoma lymphatic endothelial cells

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Zheng YP

2016-10-01

Full Text Available Yuping Zheng,1–3,* Miaomiao Sun,4,* Jinyan Chen,1,2 Lulu He,1,2 Na Zhao,1,2 Kuisheng Chen1,2 1Pathology Department, The First Affiliated Hospital of Zhengzhou University, 2Henan Key Laboratory of Tumor Pathology, 3Pathology Department, The Second Hospital of Shandong University, Jinan, 4Pathology Department, Henan Tumor Hospital, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Objective: To study the effects of vascular endothelial growth factor C small interfering RNA and endostatin on esophageal squamous cell carcinoma-related ring formation in vitro and proliferation of lymphatic endothelial cells.Materials and methods: KYSE150 cells were subjected to analysis of cell transfection and endostatin operation. The groups were as follows: negative group, blank group, negative plus endostatin group, endostatin group, SG1 group, SG2 group, SG1 plus endostatin group, and SG2 plus endostatin group. The esophageal cancer-related microlymphatic endothelial cells were three-dimensionally cultured. Cell Counting Kit-8 (CCK-8 assay was employed to detect cell proliferation.Results: The negative group’s three-dimensional culture result was the highest, followed by the blank group, negative plus endostatin group, endostatin group, SG2 group, SG1 group, SG1 plus endostatin group, and SG2 plus endostatin group. The quantity of living cells in the blank group was the highest, followed by the negative control, endostatin, SG2, SG1, negative plus endostatin, SG1 plus endostatin, and SG2 plus endostatin groups. Conclusion: Both vascular endothelial growth factor C small interfering RNA and endostatin could inhibit ring formation in esophageal squamous cell carcinoma and proliferation of lymphatic endothelial cells. Keywords: esophageal squamous carcinoma cells, esophageal cancer-associated lymphatic endothelial cells, VEGF-C, ring formation, proliferation

Mesoglycan: Clinical Evidences for Use in Vascular Diseases

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Antonella Tufano

2010-01-01

Full Text Available Vascular glycosaminoglycans (GAG are essential components of the endothelium and vessel wall and have been shown to be involved in several biologic functions. Mesoglycan, a natural GAG preparation, is a polysaccharide complex rich in sulphur radicals with strong negative electric charge. It is extracted from porcine intestinal mucosa and is composed of heparan sulfate, dermatan sulfate, electrophoretically slow-moving heparin, and variable and minimal quantities of chondroitin sulfate. Data on antithrombotic and profibrinolytic activities of the drug show that mesoglycan, although not indicated in the treatment of acute arterial or venous thrombosis because of the low antithrombotic effect, may be useful in the management of vascular diseases, when combined with antithrombotics in the case of disease of cerebral vasculature, and with antithrombotics and vasodilator drugs in the case of chronic peripheral arterial disease. The protective effect of mesoglycan in patients with venous thrombosis and the absence of side effects, support the use of GAG in patients with chronic venous insufficiency and persistent venous ulcers, in association with compression therapy (zinc bandages, multiple layer bandages, etc., elastic compression stockings, and local care, and in the prevention of recurrences in patients with previous DVT following the standard course of oral anticoagulation treatment.

[The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

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Fischer, Tamás

2015-03-01

The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

Optical coherent tomography and fluorescent microscopy for the study of meningeal lymphatic systems

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Semyachkina-Glushkovskaya, O.; Abdurashitov, A.; Namykin, A.; Fedosov, I.; Pavlov, A.; Karavaev, A.; Sindeeva, O.; Shirokov, A.; Ulanova, M.; Shushunova, N.; Khorovodov, A.; Agranovich, I.; Bodrova, A.; Sagatova, M.; Shareef, Ali Esmat; Saranceva, E.; Dvoryatkina, M.; Tuchin, V.

2018-04-01

The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo.

Vascular disease in women: comparison of diagnoses in hospital episode statistics and general practice records in England

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Wright F

2012-10-01

Full Text Available Abstract Background Electronic linkage to routine administrative datasets, such as the Hospital Episode Statistics (HES in England, is increasingly used in medical research. Relatively little is known about the reliability of HES diagnostic information for epidemiological studies. In the United Kingdom (UK, general practitioners hold comprehensive records for individuals relating to their primary, secondary and tertiary care. For a random sample of participants in a large UK cohort, we compared vascular disease diagnoses in HES and general practice records to assess agreement between the two sources. Methods Million Women Study participants with a HES record of hospital admission with vascular disease (ischaemic heart disease [ICD-10 codes I20-I25], cerebrovascular disease [G45, I60-I69] or venous thromboembolism [I26, I80-I82] between April 1st 1997 and March 31st 2005 were identified. In each broad diagnostic group and in women with no such HES diagnoses, a random sample of about a thousand women was selected for study. We asked each woman’s general practitioner to provide information on her history of vascular disease and this information was compared with the HES diagnosis record. Results Over 90% of study forms sent to general practitioners were returned and 88% of these contained analysable data. For the vast majority of study participants for whom information was available, diagnostic information from general practice and HES records was consistent. Overall, for 93% of women with a HES diagnosis of vascular disease, general practice records agreed with the HES diagnosis; and for 97% of women with no HES diagnosis of vascular disease, the general practitioner had no record of a diagnosis of vascular disease. For severe vascular disease, including myocardial infarction (I21-22, stroke, both overall (I60-64 and by subtype, and pulmonary embolism (I26, HES records appeared to be both reliable and complete. Conclusion Hospital admission data

A New Technique to Map the Lymphatic Distribution and Alignment of the Penis.

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Long, Liu Yan; Qiang, Pan Fu; Ling, Tao; Wei, Zhang Yan; Long, Zhang Yu; Shan, Meng; Rong, Li Shi; Li, Li Hong

2015-08-01

The present study was to examine the distribution of lymphatic vessels in the penis of normal adult males, which could provide an anatomical basis for improvement of incisions in penile lengthening surgery, and may also help to prevent postoperative refractory edema. Thirteen normal adult male volunteers were recruited for this study. Contrast agent was injected subcutaneously in the foreskin of the penis, and after two minutes magnetic resonance lymphangiography (MRL) was performed. The acquired magnetic resonance images were analyzed to determine the changes in the number and diameter of lymphatic vessels in different parts of the penis. Maximum intensity projections (MIP) and materializes interactive medical image control system (MIMICS) were applied to analyze the overall distribution of lymphatic vessels in the penis. Magnetic resonance imaging (MRI) showed that the lymphatic vessels were in conspicuous contrast with surrounding tissues and could be clearly identified. Penile lymphatic vessels were clearly visible in the root of the penis. At the junction of the penis and the abdominal wall, all lymphatic vessels were found to be concentrated in the dorsal part of the penis. MIP two-dimensional reconstruction showed that the overall distribution of relatively large lymphatic vessels in the dorsal and ventral parts of the penis could be seen clearly on bilateral 45° position, but not inside the abdominal wall because some of lymphatic vessels were overlapped by other tissues in the abdomen. MIMICS three-dimensional reconstruction was able to reveal the overall spatial distribution of lymphatic vessels in the penis from any angle. The reconstruction results showed that there were 1-2 main lymphatic vessels on the root of dorsal penis, which coursed along the cavernous to the first physiological curvature of the penis. Lymphatic vessels merged on both sides of the ventral penis. At the root of the penis, lymphatic vessels gradually coursed to the dorsal surface

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.

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

African Journals Online (AJOL)

Nevine M.F. El Deeb

2014-06-20

Jun 20, 2014 ... migration of connective tissue cells, and re-epithelialization of the wound ... lymphatic vessels sprouting in experimental rabbit ear wounds.9The ..... of lymphatic flow within 14 days, regaining the ability to drain fluid and ...

Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study

DEFF Research Database (Denmark)

Christoffersen, Mette; Frikke-Schmidt, Ruth; Schnohr, Peter

2011-01-01

To test the hypothesis that xanthelasmata and arcus corneae, individually and combined, predict risk of ischaemic vascular disease and death in the general population.......To test the hypothesis that xanthelasmata and arcus corneae, individually and combined, predict risk of ischaemic vascular disease and death in the general population....

Histopathologic aspects of radiation effects on lymphatic tissues and malignancies

International Nuclear Information System (INIS)

Lushbaugh, C.C.; Swartzendruber, D.C.

1976-01-01

Morphologic study with the light microscope remains our most facile and rapid means of tissue identification, diagnosis and staging of diseases, and demonstration of radiation-induced and other toxic effects. The inadequacy of its use alone, however, for the solution of biologic problems is nowhere better illustrated than in such studies on lymphatic tissues as are reported in this symposium. Nearly every classical concept concerning lymphocyte biology and disease derived by morphologic methods has been challenged or disproved in recent years by applications of nonmorphologic technologies. Studies with light and electron microscopy in combination with cell-labeling techniques, histochemical methodology, virology, immunology, and radiation biology have corrected many of our misconceptions and provided unifying concepts of lymphatic-tissue structure and function which explain anew our observations of the past. For example, nearly everyone now accepts the biologic role of viruses in what once were considered radiation-caused neoplasms in rodents, although whether the role of radiation and other physical and chemical insults in human carcinogenesis is direct or indirect is still to be elucidated. Also, the exact relations that obtain between radiation and cancer induction via viruses even in well-studied rodent systems remain to be determined; and here morphologic studies continue to play an important integrating role for the multidisciplinary studies that are required

Uric Acid, Hyperuricemia and Vascular Diseases

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Jin, Ming; Yang, Fan; Yang, Irene; Yin, Ying; Luo, Jin Jun; Wang, Hong; Yang, Xiao-Feng

2011-01-01

Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by Toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation. PMID:22201767

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

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Jerzy Laudański

2011-04-01

Full Text Available The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69. Positive LVI was significantly correlated with lymph node metastasis (p < 0.001, tumor size (p < 0.001, histological grading (p = 0.017, tumor depth (p = 0.001, and stage (p < 0.001. Multivariate logistic analysis identified LVI (p = 0.036 as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04 and overall survival (p = 0.032 in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90–97