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Sample records for ameliorates experimental lymphatic

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

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    Kenta Nakamura

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

  2. 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.

  3. Lymphatic vessel density and function in experimental bladder cancer

    International Nuclear Information System (INIS)

    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

  4. Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function

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    Gousopoulos, Epameinondas; Proulx, Steven T.; Bachmann, Samia B.; Scholl, Jeannette; Dionyssiou, Dimitris; Demiri, Efterpi; Halin, Cornelia; Dieterich, Lothar C.

    2016-01-01

    Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell–related networks, and indeed depletion of CD4+ cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema. Indeed, increased infiltration of Tregs was identified in mouse lymphedematous skin and in human lymphedema specimens. To investigate the role of Tregs during disease progression, loss-of-function and gain-of-function studies were performed. Depletion of Tregs in transgenic mice with Tregs expressing the primate diphtheria toxin receptor and green fluorescent protein (Foxp3-DTR-GFP) mice led to exacerbated edema, concomitant with increased infiltration of immune cells and a mixed TH1/TH2 cytokine profile. Conversely, expansion of Tregs using IL-2/anti–IL-2 mAb complexes significantly reduced lymphedema development. Therapeutic application of adoptively transferred Tregs upon lymphedema establishment reversed all of the major hallmarks of lymphedema, including edema, inflammation, and fibrosis, and also promoted lymphatic drainage function. Collectively, our results reveal that Treg application constitutes a potential new curative treatment modality for lymphedema. PMID:27734032

  5. Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells.

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    Wang, Shan; Li, Heng; Zhang, Min; Yue, Long-Tao; Wang, Cong-Cong; Zhang, Peng; Liu, Ying; Duan, Rui-Sheng

    2016-07-28

    Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG. PMID:27181511

  6. Flemingia macrophylla Extract Ameliorates Experimental Osteoporosis in Ovariectomized Rats

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    Hui-Ya Ho

    2011-01-01

    Full Text Available Flemingia macrophylla (Leguminosae, a native plant of Taiwan, is used as folk medicine. An in vitro study showed that a 75% ethanolic extract of F. macrophylla (FME inhibited osteoclast differentiation of cultured rat bone marrow cells, and the active component, lespedezaflavanone A (LDF-A, was isolated. It was found that oral administration of FME for 13 weeks suppressed bone loss in ovariectomized rats, an experimental model of osteoporosis. In addition, FME decreased urinary deoxypyridinoline concentrations but did not inhibit serum alkaline phosphatase activities, indicating that it ameliorated bone loss via inhibition of bone resorption. These results suggest that FME may represent a useful remedy for the treatment of bone resorption diseases, such as osteoporosis. In addition, LDF-A could be used as a marker compound to control the quality of FME.

  7. Bushen Yisui Capsule ameliorates axonal injury in experimental autoimmune encephalomyelitis

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    Ling Fang; Lei Wang; Qi Zheng; Tao Yang; Hui Zhao; Qiuxia Zhang; Kangning Li; Li Zhou; Haiyang Gong; Yongping Fan

    2013-01-01

    A preliminary clinical study by our group demonstrated Bushen Yisui Capsule (formerly cal ed Er-huang Formula) in combination with conventional therapy is an effective prescription for the treat-ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re-mains unclear. In this study, a MOG 35-55-immunized C57BL/6 mouse model of experimental au-toimmune encephalomyelitis was intragastrical y administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim-mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of rege-neration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.

  8. Augmenting DAF levels in vivo ameliorates experimental autoimmune encephalomyelitis.

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    Li, Qing; Huang, Danping; Nacion, Kristine; Bu, Hong; Lin, Feng

    2009-09-01

    Recent studies in experimental autoimmune encephalomyelitis (EAE) have found that CNS injury in Daf1(-/-) mice is much greater than in wild types (WTs), suggesting that upregulating DAF levels in vivo might ameliorate disease. To test this, we generated a Daf1 transgenic (Tg) mouse which had elevated DAF levels on its cell surfaces. In by-stand C3b uptake assays, Daf1 Tg mouse erythrocytes took up less C3b on their surfaces than WT erythrocytes. When co-cultured with OT-II CD4(+) T cells together with OVA(323-339) peptide, Daf1 Tg mouse bone marrow derived dendritic cells (BM-DCs) produced less C5a and C3a than WT BM-DCs and stimulated a lesser T cell response. In MOG(35-55) immunization induced EAE model, Daf1 Tg mice exhibited delayed disease onset and decreased clinical scores compared to WTs. Histological analyses showed that there were less inflammation and demyelination in spinal cords in Daf1 Tg mice than those in WTs. In accordance with these results, Daf1 Tg mice had decreased MOG(35-55) specific Th1 and Th17 responses. These data provide further evidence that DAF suppresses autoreactive T cell responses in EAE, and indicate that augmenting its expression levels could be effective therapeutically in treating multiple sclerosis as well as other T cell mediated diseases. PMID:19660813

  9. Triptolide ameliorates colonic fibrosis in an experimental rat model.

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    Tao, Qingsong; Wang, Baochai; Zheng, Yu; Li, Guanwei; Ren, Jianan

    2015-08-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn's disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS daily (control) simultaneously. Extracellular matrix (ECM) deposition in the colon was examined with image analysis of Masson Trichrome staining. Total collagen levels in colonic homogenates were measured by a Sircol assay. Collagen Iα1 transcripts and collagen I protein were measured ex vivo in the isolated colonic subepithelial myofibroblasts by reverse transcription-quantitative polymerase chain reaction and immunoblot analysis, respectively. The results indicated that triptolide decreased ECM deposition and collagen production in the colon, and inhibited collagen Iα1 transcripts and collagen I protein expression in the isolated subepithelial myofibroblasts of the rats with colonic fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the experimental rat model, suggesting triptolide may be a promising compound for inflammatory bowel disease treatment. PMID:25845760

  10. Polymerase I pathway inhibitor ameliorates experimental autoimmune encephalomyelitis.

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    Achiron, Anat; Mashiach, Roi; Zilkha-Falb, Rina; Meijler, Michael M; Gurevich, Michael

    2013-10-15

    Applying high throughput gene expression microarrays we identified that the suppression of polymerase 1 (POL1) pathway is associated with benign course of multiple sclerosis (MS). This finding supports the rationale for direct targeting of the POL1 transcription machinery as an innovative strategy to suppress MS. To evaluate the effects of a specific polymerase I inhibitor (POL1-I) on experimental autoimmune encephalomyelitis (EAE), we immunized female C57BL/6J mice (8 weeks) with MOG35-55/CFA. A new POL1-I was administered at a daily dose of 12.5mg/kg body weight by oral gavage either from the day of immunization until disease onset (EAE score 1.0, immunization model), at disease onset (EAE score=1.0) for the following 14 days (treatment model), or by alternate daily dose of 25.0mg/kg body weight, by oral gavage from the day of immunization for the following 25 days (combined model). POL1-I remarkably suppressed EAE in the immunization model; while in the Vehicle group the onset of EAE occurred on day 10.0±0.4 with maximal clinical score of 3.2±0.2, in the POL1-I treated mice onset was significantly delayed and occurred on day 16.9±1.1 (p=0.001), and maximal disease score 2.0±0.1 was reduced (p=0.004). In the treatment model POL1-I treatment significantly reduced disease activity; maximal score was 2.0±0.5 while in the Vehicle group it reached a mean maximal score of 3.9±0.1, (p=0.0008). In the combined model, POL1-I treatment completely inhibited disease activity. The effect of POL1-I treatment was modulated through decreased expression of POL1 pathway key-related genes LRPPRC, pre-RNA, POLR1D and RRN3 together with activation of P53 dependent apoptosis of CD4+ splenocytes. Our findings demonstrate that POL1 pathway inhibition delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs.

  11. Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model

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    Haisheng Liu; Zhili Ni; Yetao Chen; Dong Wang; Yan Qi; Qiuhang Zhang; Shijie Wang

    2012-01-01

    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil(R) (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.

  12. Lymphatic Filariasis

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    ... CDC Cancel Submit Search The CDC Parasites - Lymphatic Filariasis Note: Javascript is disabled or is not supported ... please visit this page: About CDC.gov . Lymphatic Filariasis General Information Frequently Asked Questions (FAQs) Vectors of ...

  13. Mechanisms of lymphatic regeneration after tissue transfer.

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    Alan Yan

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

  14. Fatty Acid Synthase Inhibitor C75 Ameliorates Experimental Colitis

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    Matsuo, Shingo; Yang, Weng-Lang; Aziz, Monowar; Kameoka, Shingo; Wang, Ping

    2013-01-01

    Abnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activity. We hypothesized that C75 treatment could effectively reduce the severity of experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS) for 7 d. C75 (5 mg/kg body weight) or...

  15. Silencing MicroRNA-155 Ameliorates Experimental Autoimmune Encephalomyelitis

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    Murugaiyan, Gopal; Beynon, Vanessa; Mittal, Akanksha; Joller, Nicole; Howard L Weiner

    2011-01-01

    IFN-γ–producing Th1 and IL-17–producing Th17 cells are the key participants in various autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Although both of these T cell subsets are known to be regulated by specific transcription factors and cytokines, the role of microRNAs that control these two inflammatory T cell subsets and whether targeting microRNAs can have therapeutic effects are not known. In this study, we show that...

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

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    Armando Angelo Casaroli

    2011-01-01

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

  17. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis.

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    Murugaiyan, Gopal; Beynon, Vanessa; Mittal, Akanksha; Joller, Nicole; Weiner, Howard L

    2011-09-01

    IFN-γ-producing Th1 and IL-17-producing Th17 cells are the key participants in various autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Although both of these T cell subsets are known to be regulated by specific transcription factors and cytokines, the role of microRNAs that control these two inflammatory T cell subsets and whether targeting microRNAs can have therapeutic effects are not known. In this study, we show that microRNA-155 (Mir-155) expression is elevated in CD4(+) T cells during EAE, and Mir-155(-/-) mice had a delayed course and reduced severity of disease and less inflammation in the CNS. The attenuation of EAE in Mir-155(-/-) mice was associated with a decrease in Th1 and Th17 responses in the CNS and peripheral lymphoid organs. The T cell-intrinsic function of Mir-155(-/-) was demonstrated by the resistance of Mir-155(-/-) CD4(+) T cell-repleted Rag-1(-/-) mice to EAE. Finally, we found that anti-Mir-155 treatment reduced clinical severity of EAE when given before and after the appearance of clinical symptoms. These findings demonstrate that Mir-155 confers susceptibility to EAE by affecting inflammatory T cell responses and identify Mir-155 as a new target for therapeutic intervention in multiple sclerosis. PMID:21788439

  18. Macrofilaricidal activity and amelioration of lymphatic pathology in bancroftian filariasis after 3 weeks of doxycycline followed by single-dose diethylcarbamazine.

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    Mand, Sabine; Pfarr, Kenneth; Sahoo, Prakash K; Satapathy, Ashok K; Specht, Sabine; Klarmann, Ute; Debrah, Alexander Y; Ravindran, Balachandran; Hoerauf, Achim

    2009-10-01

    In a placebo controlled trial, the effects of 21- and 10-day doxycycline treatments (200 mg/day) followed by single dose diethylcarbamazine (administered 4 months post treatment) on depletion of Wolbachia endobacteria from Wuchereria bancrofti, filaricidal activity, and amerlioration of scrotal lymph vessel dilation were studied in 57 men from Orissa, India. The 21-day doxycycline course reduced Wolbachia in W. bancrofti by 94% before diethylcarbamazine administration. After 12 months, all patients with this treatment were amicrofilaremic and different from the 10-day doxycycline (42.9%) and placebo (37.5%) groups, and significantly fewer were positive for scrotal worm nests (6.7%) compared with 10-day doxycycline (60%) and placebo (66.7%). Average scrotal lymph vessel diameters were reduced from 0.7 cm pre-treatment to 0.02 cm in patients after 21 days of treatment, while no significant changes were seen in the other groups. This latter feature confirms the beneficial effects of doxycycline on lymphatic dilation and thus adds to the existing evidence that doxycycline, in addition to being macrofilaricidal, may be used to prevent or reverse lymphatic pathology. PMID:19815891

  19. Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis

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    Yifat Amir-Levy

    2014-01-01

    Full Text Available Background. The neural stem cells (NSCs migrate to the damaged sites in multiple sclerosis (MS and in experimental autoimmune encephalomyelitis (EAE. However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU+GFAP+ NSCs to BrdU+DCX+ neuroblasts in the subventricular zone (SVZ, increased BrdU+NeuN+ neurons in the granular cell layer of the dentate gyrus, and increased BrdU+O4+ oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS.

  20. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice.

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    Sun, Jun-Jun; Ren, Qing-Guo; Xu, Lin; Zhang, Zhi-Jun

    2015-09-18

    More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients.

  1. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats.

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    Meena, Sunita; Rajput, Yudhishthir S; Pandey, Amit K; Sharma, Rajan; Singh, Raghvendar

    2016-08-01

    This study was designed to assess anti-diabetic potential of goat, camel, cow and buffalo milk in streptozotocin (STZ) induced type 1 diabetic albino wistar rats. A total of 48 rats were taken for the study where one group was kept as non-diabetic control group (8 rats) while others (40 rats) were made diabetic by STZ (50 mg/kg of body weight) injection. Among diabetic rats, a control group (8 rats) was kept and referred as diabetic control whereas other four groups (8 rats each) of diabetic rats were fed on 50 ml of goat or camel or cow or buffalo milk for 4 weeks. All the rats (non-diabetic and diabetic) were maintained on standard diet for four weeks. STZ administration resulted in enhancement of glucose, total cholesterol, triglyceride, low density lipoprotein, HbA1c and reduction in high density lipoprotein in plasma and lowering of antioxidative enzymes (catalase, glutathione peroxidase and superoxide dismutase) activities in pancreas, kidney, liver and RBCs, coupled with enhanced levels of TBARS and protein carbonyls in pancreas, kidney, liver and plasma. OGTT carried out at the end of 4 week milk feeding indicated that all milks helped in early maintenance of glucose level. All milks reduced atherogenic index. In camel milk fed diabetic group, insulin concentration enhanced to level noted for non-diabetic control while goat, cow and buffalo milk failed to restore insulin level. HbA1c level was also restored only in camel milk fed diabetic group. The level of antioxidative enzymes (catalase, GPx and SOD) in pancreas enhanced in all milk fed groups. Camel milk and to a reasonable extent goat milk reduced formation of TBARS and PCs in tissues and blood. It can be concluded that camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. Further, only camel milk completely ameliorated oxidative damage in pancreas and normalised insulin level. PMID:27600979

  2. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

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    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  3. Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection.

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    Kalliopi Pitarokoili

    Full Text Available Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system.Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53-78 of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN.We conclude that immunomodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.

  4. Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Tomohiro Kudo; Shinichi Okamura; Yajing Zhang; Takashige Masuo; Masatomo Mori

    2011-01-01

    AIM: To examine the efficacy of glycyrrhizin preparation (GL-p) in the treatment of a rat model of ulcerative colitis (UC). METHODS: Experimental colitis was induced by oral administration of dextran sodium sulfate. Rats with colitis were intrarectally administered GL-p or saline. The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score. The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis. The effect of GL-p on myeloperoxidase (MPO) activity in the inflamed mucosa and purified enzyme was assayed. RESULTS: GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline. Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin (IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa. Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO. CONCLUSION: GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

  5. Pulmonary lymphatics and radiation

    International Nuclear Information System (INIS)

    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

  6. Ameliorating effects of antioxidative compounds from four plant extracts in experimental models of diabetes

    Directory of Open Access Journals (Sweden)

    Dinić Svetlana

    2013-01-01

    Full Text Available Given that oxidative stress plays a major role in pancreatic β-cell dysfunction and ultimate destruction, as well as in different complications of diabetes, therapy with antioxidants has assumed an important place in diabetes management. The relatively limited effects of established antioxidant compounds have stimulated efforts to develop new therapeutic strategies, e.g. to increase the endogenous antioxidant defenses through pharmacological modulation of key antioxidant enzymes. Plant extracts are gaining popularity in treating diabetes because many substances synthesized by higher plants and fungi possess antioxidant activities and can prevent or protect tissues against the damaging effects of free radicals. This review summarizes experimental models of diabetes and possible mechanisms that lie behind the antioxidative effects of α-lipoic acid (LA, a powerful antioxidant and compound that stimulates cellular glucose uptake, as well as of plant extracts from sweet chestnut (Castanea sativa, edible mushroom (Lactarius deterrimus and natural products containing β-glucans in the treatment of diabetes. Their roles in preventing pancreatic β-cell death and in ameliorating the effects of severe diabetic complications are discussed. [Projekat Ministarstva nauke Republike Srbije, br. 173020

  7. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats

    Institute of Scientific and Technical Information of China (English)

    Ru-Tao Hong; Jian-Ming Xu; Qiao Mei

    2009-01-01

    AIM:To investigate the protective effects of melatonin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats. METHODS:All rats were randomly divided into normal control group, model control group treated with CCl4 for 12 wk, CCl4 + NAC group treated with CCl4 + NAC (100 mg/kg, i.p.) for 12 wk, CCl4 + MEL-1 group treated with CCl4 + melatonin (2.5 mg/kg) for 12 wk, CCl4 + MEL-2 group treated with CCl4 + melatonin (5.0 mg/kg) for 12 wk, and CCl4 + MEL-3 group treated with CCl4 + melatonin (10 mg/kg). Rats in the treatment groups were injected subcutaneously with sterile CCl4 (3 mL/kg, body weight) in a ratio of 2:3 with olive oil twice a week. Rats in normal control group received hypodermic injection of olive oil at the same dose and frequency as those in treatment groups. At the end of experiment, rats in each group were anesthetized and sacrificed. Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine changes in liver pathology. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and protein concentration were measured with routine laboratory methods using an autoanalyzer. Hydroxyproline (HYP) content in liver and malondialdehyde (MDA) and glutathione peroxidase (GPx) levels in liver homogenates were assayed by spectrophotometry. Serum hyaluronic acid (HA), laminin (LN), and procollagen Ⅲ N-terminal peptide (PⅢNP) were determined by radioimmunoassay. RESULTS:Pathologic grading showed that the fibrogenesis was much less severe in CCl4 + MEL3 group than in model control group ( u = 2.172, P < 0.05), indicating that melatonin (10 mg/kg) can significantly ameliorate CCl4-induced hepatic fibrotic changes. The serum levels of ALT and AST were markedly lower in CCl4 + MEL treatment groups (5, 10 mg/kg) than in model control group (ALT:286.23 serum laminin (LN) and hyaluronic acid (HA) levels and hydroxyproline (HYP) contents in liver were significantly lower in CCl4 + MEL-3 group (10

  8. Mesenchymal stem cells transplantation mildly ameliorates experimental diabetic nephropathy in rats

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hong; TIAN Hao-ming; LONG Yang; ZHANG Xiang-xun; ZHONG Li; DENG Li; CHEN Xiao-he; LI Xiu-qun

    2009-01-01

    Background Diabetic nephropathy is a common complication of diabetes mellitus.This study aimed to explore whether mesenchymal stem cells(MSCs)transplantation could attenuate diabetic nephropathy in experimental diabetic rats.Methods Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin(STZ)(60 mg/kg).Diabetic rats were randomized to four groups:diabetes control group(DC),ciclosporin A group(CsA),MSC group,and MSC+CsA group(MSCA).Bone marrow mesenchymal stern cells were cultured,identified and labeled by 5-bromo-2'-deoxyuridine(BrdU)in vitro.Then they were transplanted to diabetic rats via introcardiac infusion.Ciclosporin A was administered daily at 5 mg/kg.At 1,2,4,8 weeks after transplantation,random blood glucose,urine albumin/creatinine ratio(Alb/Cr),endogenous creatinine clearance rate and renal mass index were tested.Renal morphology and labeled cells were examined.Results Cultured MSCs expressed mesenchymal cell phenotype,and could be multidifferentiated to osteogenic and adipogenic cells.Labeled MSCs could be detected in the kidney of nephropathic rats,mainly in renal interstitium,but they did not propagate after engrafting in kidney.Over the course of the experiment,MSCA group showed a significant decrease in blood glucose compared with MSC group,CsA group and DC group(P<0.05,respectively).The Alb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group(P<0.05).And the Alb/Cr in MSCA group showed a significant decrease compared with MSC group(0.74 vs 0.84,P<0.05).There was a significant difference in renal mass index between the MSCA group and DC group(5.66 vs 6.37,P<0.05).No significant difference was found in creatinine clearance rate among 4 groups(P>0.05).Treatment with MSC+CsA significantly ameliorated the morphology of diabetic kidney.Conclusion MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose,Alb/Cr ratio and renal mass index.

  9. Anatomy of the lymphatics.

    Science.gov (United States)

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

    2007-01-01

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

  10. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  11. Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model.

    Directory of Open Access Journals (Sweden)

    Sun Woo Lim

    Full Text Available BACKGROUND: This study was performed to investigate whether ginseng has a protective effect in an experimental mouse model of cyclosporine-induced pancreatic injury. METHODS: Mice were treated with cyclosporine (30 mg/kg/day, subcutaneously and Korean red ginseng extract (0.2 or 0.4 g/kg/day, oral gavage for 4 weeks while on a 0.01% salt diet. The effect of ginseng on cyclosporine-induced pancreatic islet dysfunction was investigated by an intraperitoneal glucose tolerance test and measurements of serum insulin level, β cell area, macrophage infiltration, and apoptosis. Using an in vitro model, we further examined the effect of ginseng on a cyclosporine-treated insulin-secreting cell line. Oxidative stress was measured by the concentration of 8-hydroxy-2'-deoxyguanosine in serum, tissue sections, and culture media. RESULTS: Four weeks of cyclosporine treatment increased blood glucose levels and decreased insulin levels, but cotreatment with ginseng ameliorated the cyclosporine-induced glucose intolerance and hyperglycemia. Pancreatic β cell area was also greater with ginseng cotreatment compared with cyclosporine monotherapy. The production of proinflammatory molecules, such as induced nitric oxide synthase and cytokines, and the level of apoptotic cell death also decreased in pancreatic β cell with ginseng treatment. Consistent with the in vivo results, the in vitro study showed that the addition of ginseng protected against cyclosporine-induced cytotoxicity, inflammation, and apoptotic cell death. These in vivo and in vitro changes were accompanied by decreases in the levels of 8-hydroxy-2'-deoxyguanosine in pancreatic β cell in tissue section, serum, and culture media during cotreatment of ginseng with cyclosporine. CONCLUSIONS: The results of our in vivo and in vitro studies demonstrate that ginseng has a protective effect against cyclosporine-induced pancreatic β cell injury via reducing oxidative stress.

  12. Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model.

    Science.gov (United States)

    Sil, Rajarshi; Ray, Doel; Chakraborti, Abhay Sankar

    2015-11-01

    Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60%) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome. PMID:26400710

  13. Alpha-tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells

    Directory of Open Access Journals (Sweden)

    Haikuo Xue

    2016-05-01

    Full Text Available Objective(s: Multiple sclerosis (MS is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E is an important component of human diet with antioxidant activity, which protects the body’s biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE, the animal model of MS, and treated EAE with α-tocopherol (AT which is the main content of Vit E. Materials and Methods:Twenty C57BL/6 adult female mice were used and divided into two groups randomly. EAE was induced with myelin oligodendrocyte glycoprotein (MOG, and one group was treated with AT, at a dose of 100 mg/kg on the 3th day post-immunization with MOG, the other group was treated with 1% alcohol. Mice were euthanized on day 14, post-immunization, spleens were removed for assessing splenocytes proliferation and cytokine profile, and spinal cords were dissected to assess the infiltration of inflammatory cells in spinal cord. Results:AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-γ (Th1 cytokine, though the other cytokines were only affected slightly. Conclusion:According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS.

  14. Spleen and Lymphatic System

    Science.gov (United States)

    ... Help a Friend Who Cuts? Spleen and Lymphatic System KidsHealth > For Teens > Spleen and Lymphatic System Print A A A Text Size What's in ... en español Bazo y sistema linfático The lymphatic system is an extensive drainage network that helps keep ...

  15. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury.

    Science.gov (United States)

    Li, Guo-Yu; Zheng, Ya-Xin; Sun, Fu-Zhou; Huang, Jian; Lou, Meng-Meng; Gu, Jing-Kai; Wang, Jin-Hui

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury. PMID:26389883

  16. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

    Directory of Open Access Journals (Sweden)

    Guo-Yu Li

    2015-09-01

    Full Text Available This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory in acute liver injury. Pathological observation, reactive oxygen species (ROS detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS. Similarity ensemble approach (SEA docking, molecular modeling, molecular docking, and molecular dynamics (MD simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.

  17. Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration.

    Science.gov (United States)

    Choi, Inho; Lee, Yong Suk; Chung, Hee Kyoung; Choi, Dongwon; Ecoiffier, Tatiana; Lee, Ha Neul; Kim, Kyu Eui; Lee, Sunju; Park, Eun Kyung; Maeng, Yong Sun; Kim, Nam Yun; Ladner, Robert D; Petasis, Nicos A; Koh, Chester J; Chen, Lu; Lenz, Heinz-Josef; Hong, Young-Kwon

    2013-01-01

    Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.

  18. Ameliorative effects of arctiin from Arctium lappa on experimental glomerulonephritis in rats.

    Science.gov (United States)

    Wu, Jian-Guo; Wu, Jin-Zhong; Sun, Lian-Na; Han, Ting; Du, Jian; Ye, Qi; Zhang, Hong; Zhang, Yu-Guang

    2009-11-01

    Membranous glomerulonephritis (MGN) remains the most common cause of adult-onset nephrotic syndrome in the world and up to 40% of untreated patients will progress to end-stage renal disease. Although the treatment of MGN with immunosuppressants or steroid hormones can attenuate the deterioration of renal function, numerous treatment-related complications have also been established. In this study, the ameliorative effects of arctiin, a natural compound isolated from the fruits of Arctium lappa, on rat glomerulonephritis induced by cationic bovine serum albumin (cBSA) were determined. After oral administration of arctiin (30, 60, 120 mg/kgd) for three weeks, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and 24-h urine protein content markedly decreased, while endogenous creatinine clearance rate (ECcr) significantly increased. The parameters of renal lesion, hypercellularity, infiltration of polymorphonuclear leukocyte (PMN), fibrinoid necrosis, focal and segmental proliferation and interstitial infiltration, were reversed. In addition, we observed that arctiin evidently reduced the levels of malondialdehyde (MDA) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha), suppressed nuclear factor-kappaB p65 (NF-kappaB) DNA binding activity, and enhanced superoxide dismutase (SOD) activity. These findings suggest that the ameliorative effects of arctiin on glomerulonephritis is carried out mainly by suppression of NF-kappaB activation and nuclear translocation and the decreases in the levels of these pro-inflammatory cytokines, while SOD is involved in the inhibitory pathway of NF-kappaB activation. Arctiin has favorable potency for the development of an inhibitory agent of NF-kappaB and further application to clinical treatment of glomerulonephritis, though clinical studies are required.

  19. Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2013-08-15

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

  20. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  1. MDA—Lymphatic Filariasis

    OpenAIRE

    Ichimori, Kazuyo

    2014-01-01

    Lymphatic filariasis is one of the neglected tropical diseases. It is estimated that 120 million people are currently infected in 73 countries where filariasis is endemic. Lymphatic filariasis is a leading cause of chronic disability worldwide, including of 15 million people who have lymphoedema (elephantiasis) and 25 million men who have hydrocoele.

  2. MDA—Lymphatic Filariasis

    Science.gov (United States)

    2014-01-01

    Lymphatic filariasis is one of the neglected tropical diseases. It is estimated that 120 million people are currently infected in 73 countries where filariasis is endemic. Lymphatic filariasis is a leading cause of chronic disability worldwide, including of 15 million people who have lymphoedema (elephantiasis) and 25 million men who have hydrocoele. PMID:25425947

  3. Thalidomide ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in an experimental model.

    Science.gov (United States)

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-04-01

    Cisplatin is a platinum-based chemotherapy drug. However, its chemotherapeutic use is restricted by serious side effects, especially nephrotoxicity. Inflammatory mechanisms have a significant role in the pathogenesis of cisplatin-induced nephrotoxicity. Thalidomide is an immunomodulatory and anti-inflammatory agent and is used for the treatment of various inflammatory diseases. The purpose of this study was to investigate the potential nephroprotective effect of thalidomide in a mouse model of cisplatin-induced nephrotoxicity. Nephrotoxicity was induced in mice by a single injection of cisplatin (15 mg/kg, i.p.) and treated with thalidomide (50 and 100 mg/kg/day, orally) for 4 days, beginning 24 h prior to the cisplatin injection. Renal toxicity induced by cisplatin was demonstrated by increasing plasma levels of creatinine and blood urea nitrogen (BUN). Cisplatin increased the renal production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β1. In addition, kidney levels of malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) were increased by cisplatin. Biochemical results showed that thalidomide reduced cisplatin-induced increase in plasma creatinine and BUN. Thalidomide treatment also significantly reduced tissue levels of the proinflammatory cytokines, MDA, MPO, and NO and increased anti-inflammatory cytokine IL-10. Furthermore, histological examination indicated that thalidomide ameliorated renal damage caused by cisplatin. These data suggest that thalidomide attenuates cisplatin-induced nephrotoxicity possibly by inhibition of inflammatory reactions. Taken together, our findings indicate that thalidomide might be a valuable candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  5. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  6. A Mushroom Extract Piwep from Phellinus igniarius Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Immune Cell Infiltration in the Spinal Cord

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    Lan Li

    2014-01-01

    Full Text Available The present study aimed to evaluate the therapeutic potential of a mushroom extract from Phellinus igniarius in an animal model of multiple sclerosis. The medicinal mushroom, Phellinus igniarius, contains biologically active compounds that modulate the human immune system. Experimental autoimmune encephalomyelitis (EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG 35–55 in C57BL/6 female mice. A water-ethanol extract of Phellinus igniarius (Piwep was delivered intraperitoneally every other day for the entire experimental course. Three weeks after the initial immunization, demyelination and immune cell infiltration in the spinal cord were examined. Piwep injection profoundly decreased the daily incidence rate and clinical score of EAE. The Piwep-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, macrophages, and B cells in the spinal cord. Piwep reduced expression of vascular cell adhesion molecule-1 (VCAM-1 in the spinal cord and integrin-α4 in the lymph node of EAE mice. Piwep also inhibited proliferation of lymphocytes and secretion of interferon-γ in the lymph node of EAE mice. The results suggest that a mushroom extract, Piwep, may have a high therapeutic potential for ameliorating multiple sclerosis progression.

  7. Evaluating the efficacy of rBmHATαc as a multivalent vaccine against lymphatic filariasis in experimental animals and optimizing the adjuvant formulation

    Science.gov (United States)

    Dakshinamoorthy, Gajalakshmi; Kalyanasundaram, Ramaswamy

    2013-01-01

    Developing an effective vaccine against lymphatic filariasis will complement the WHO's effort to eradicate the infection from endemic areas. Currently 83 different countries are endemic for this infection and over 1 billion people are at risk. An effective vaccine coupled with mass drug administration will reduce the morbidity and social stigma associated with this gruesome disease. Several potential vaccine candidates that can confer partial protection in experimental animals have been reported from different laboratories. However, no licensed vaccines are currently available for this disease. Among the several vaccine antigens identified from our laboratory, three most promising antigens; rBmHSPαc (α crystalline domain and c-terminal extension of Heat Shock Protein 12.6), rBmALT-2 (Abundant larval transcript) and rBmTSP LEL (Tetraspanin large extracellular loop) was further developed as a recombinant fusion protein vaccine (rBmHATαc). In a mouse model this fusion protein vaccine gave close to 68% protection following a challenge infection. To improve the vaccine efficiency of rBmHATαc, in this study we evaluated various preparations of alum (AL007, AL019, Alhydrogel and Imject® Alum) as adjuvants. Our results show that mice immunized with rBmHATαc formulated in AL007 (alum from IDRI) and/or AL019 (alum plus TLR-4 agonist from IDRI) gave the highest IgG antibody titer compared to other groups. Subsequent in vivo challenge experiments confirmed that >95% protection can be achieved when AL007 or AL019 was used as the adjuvant. However, when Imject® Alum or alhydrogel was used as the adjuvant only 76% and 72% protection respectively could be achieved. These results show that AL007 or AL019 (IDRI) is an excellent choice of adjuvant for the rBmHATαc vaccine against B. malayi L3 in mice. PMID:24211167

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Simvastatin ameliorates low-dose streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model.

    Science.gov (United States)

    Zhang, Siwei; Xu, Huali; Yu, Xiaofeng; Wang, Yuchen; Sun, Fanfan; Sui, Dayuan

    2015-01-01

    The present study aims to study the possible renal protective effect of simvastatin in the development and progression of type 2 diabetic nephropathy. A rat model of T2DN was induced by high-fat diet together with single low-dose of streptozotocin. The diabetic rats were either given treatment or vehicle control for 13 weeks to develop nephropathy. At the end of treatment, parameters of renal function were determined. Kidney samples were collected for histological studies and generated homogenates for biochemical analysis. In T2DN rats, severe hyperglycemia was developed, FBG were markedly elevated. Diabetes induced significant alterations in renal structure, such as severe reduction of glomerular tufts, increase in Bowman's spaces, thickening of GBM. In addition, and SCr, UAER and BUN are elevated, accompanied with reduction in UCr and CCr, indicating obvious renal failure. On the other hand, endogenous antioxidants SOD, GSH-Px were reduced, whereas MDA was increased. However, treatment of T2DN rats with simvastatin restored renal changes in different aspects. Our results showed that STZ-induced T2DN could be attenuated by simvastatin. The renoprotective effects of simvastatin was indicated by improvements in kidney function parameters, and was attributed by its lipid-lowering effect as well as its anti-oxidative stress, anti-inflammatory properties without having noticeable influence on glycemic control. Simvastatin ameliorates low-dose Streptozotocin-induced type 2 diabetic nephropathy in an experimental rat model. PMID:26131264

  10. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.

    Directory of Open Access Journals (Sweden)

    Kamaldeen A Muili

    Full Text Available BACKGROUND: The approved immunomodulatory agents for the treatment of multiple sclerosis (MS are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE model of multiple sclerosis. METHODOLOGY/PRINCIPAL FINDINGS: The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α and up-regulation of anti-inflammatory cytokines (IL-4, IL-10 in vitro and in vivo. CONCLUSION/SIGNIFICANCE: These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.

  11. LONG TERM EFFECTS OF AMELIORATIVE WORKS ON SOME SOIL QUALITY PARAMETERS FROM BAIA –MOLDOVA EXPERIMENTAL AGRICULTURAL DRAINAGE FIELD

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    V. Moca

    2009-10-01

    Full Text Available The soil-climatic conditions from Baia Depression – the hydrographical basin from the extra-Carpathian area of the Moldova River - have frequently determined the presence, under different forms, intensities and periods, of temporary water excess from soil. The underground drainage, as a measure of water excess control, with stagnant character, caused mainly by rainfall amounts registered for 1-5 consecutive days, was firstly arranged in pilot-experimental fields during 1972-1978. We followed the behaviour in exploitation of underground drainage technical solutions, as concerns the functional efficiency of the means of water excess removal and of the improved soil favourableness and/or suitability for crop growing.In order to assess the long-term effects of ameliorating works, applied in 1978 in the drainage field of Baia, on an area of 3.50 ha, we have qualitatively classified and estimated the albic stagnic glossic Luvosoil (S.R.T.S. – 2003, improved and unimproved. Based on this study, we have estimated the present favourableness for crops of the improved soil, as compared to unimproved soil, used as natural grassland, after an exploitation cycle of 30 years (1978- 2008.

  12. Proteasome Inhibitor Bortezomib Suppresses Nuclear Factor-Kappa B Activation and Ameliorates Eye Inflammation in Experimental Autoimmune Uveitis

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    Sheng-Min Hsu

    2015-01-01

    Full Text Available Bortezomib is a proteasome inhibitor used for hematologic cancer treatment. Since it can suppress NF-κB activation, which is critical for the inflammatory process, bortezomib has been found to possess anti-inflammatory activity. In this study, we evaluated the effect of bortezomib on experimental autoimmune uveitis (EAU in mice and investigated the potential mechanisms related to NF-κB inactivation. High-dose bortezomib (0.75 mg/kg, low-dose bortezomib (0.15 mg/kg, or phosphate buffered saline was given after EAU induction. We found that the EAU is ameliorated by high-dose bortezomib treatment when compared with low-dose bortezomib or PBS treatment. The DNA-binding activity of NF-κB was suppressed and expression of several key inflammatory mediators including TNF-α, IL-1α, IL-1β, IL-12, IL-17, and MCP-1 was lowered in the high-dose bortezomib-treated group. These results suggest that proteasome inhibition is a promising treatment strategy for autoimmune uveitis.

  13. Rituximab therapy reduces organ-specific T cell responses and ameliorates experimental autoimmune encephalomyelitis.

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    Nancy L Monson

    Full Text Available Recent clinical trials have established B cell depletion by the anti-CD20 chimeric antibody Rituximab as a beneficial therapy for patients with relapsing-remitting multiple sclerosis (MS. The impact of Rituximab on T cell responses remains largely unexplored. In the experimental autoimmune encephalomyelitis (EAE model of MS in mice that express human CD20, Rituximab administration rapidly depleted peripheral B cells and strongly reduced EAE severity. B cell depletion was also associated with diminished Delayed Type Hypersensitivity (DTH and a reduction in T cell proliferation and IL-17 production during recall immune response experiments. While Rituximab is not considered a broad immunosuppressant, our results indicate a role for B cells as a therapeutic cellular target in regulating encephalitogenic T cell responses in specific tissues.

  14. FMS-like tyrosine kinase 3 ligand treatment does not ameliorate experimental rapidly progressive glomerulonephritis.

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    Joanna R Ghali

    Full Text Available Fms-like tyrosine kinase 3-ligand (FL is a growth factor that may expand dendritic cell and regulatory T cell populations. We hypothesised that FL-induced regulatory T cells would protect mice from experimental rapidly progressive glomerulonephritis. To determine if FL was able to enhance regulatory T cell populations, C57BL/6 mice received 10 days of daily intraperitoneal injections of either FL or phosphate buffered saline. To induce accelerated autologous-phase anti-mouse glomerular basement membrane glomerulonephritis, mice were sensitized to sheep globulin 4 days prior to the induction of glomerulonephritis with sheep anti-mouse glomerular basement membrane globulin, and experiments ended 10 days later. FL was administered before, throughout and during the sensitization phase of this glomerulonephritis model. Renal disease and systemic immunity to the nephritogenic antigen were assessed. FL increased regulatory T cell and plasmacytoid dendritic cell proportions within spleen and lymph nodes. FL administration prior to glomerulonephritis did not protect mice from renal injury. When FL was given throughout the model, FL treated mice had reduced survival, with more interstitial neutrophils and glomerular CD11c+ cells than controls. Systemic immune responses showed increased IL-17A production from splenocytes, with more CD11c+ cells, but reduced plasmacytoid dendritic cell proportions in spleen and lymph nodes, despite increased regulatory T cell proportions. Under homeostatic conditions, FL expanded regulatory T cell and plasmacytoid dendritic cell populations, but FL enhanced systemic inflammatory responses and conventional dendritic cell populations when given during experimental glomerulonephritis, suggesting selective attempts to suppress pathogenic immunity by dendritic cell manipulation may be harmful.

  15. Lymphatic Filariasis: Frequently Asked Questions (FAQs)

    Science.gov (United States)

    ... the treatment for lymphatic filariasis? What is lymphatic filariasis? Lymphatic filariasis is a parasitic disease caused by ... worms in the United States. How is lymphatic filariasis spread? The disease spreads from person to person ...

  16. Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity

    Institute of Scientific and Technical Information of China (English)

    Osamu Kanauchi; Masanobu Fukuda; Yoshiaki Matsumoto; Shino Ishii; Toyokazu Ozawa; Makiko Shimizu; Keiichi Mitsuyama; Akira Andoh

    2006-01-01

    AIM: To examine the effect of Eubacterium limosum (E.limosum) on colonic epithelial cell line in vitro, and to evaluate the effect of E.limosum on experimental colitis.METHODS: E.limosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E.limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 (TLR4) was evaluated by real time PCR.Colitis was induced by feeding BALB/C mice with 2.0%dextran sodium sulfate. These mice received either 5%lyophilized E.limosum (n = 7) or control diet (n = 7).Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.RESULTS: The E.limosum produced butyrate, acetate,propionate, and lactate at 0.25, 1.0, 0.025 and 0.07mmol/L, respectively in medium. At this concentration,each acid had no growth stimulating activity on T84cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1mmol/L. In addition, under TNF-α stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E.limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.CONCLUSION: E.limosum can ameliorate experimental colonic inflammation. In part, the metabolite of E.limosum, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.

  17. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    International Nuclear Information System (INIS)

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys3]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation

  18. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

  19. Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome

    Science.gov (United States)

    Xu, Duo; Chen, Bing; Gu, Jianteng; Chen, Lin; Belguise, Karine; Wang, Xiaobo; Yi, Bin; Lu, Kaizhi

    2016-01-01

    Hepatopulmonary syndrome (HPS) is a defective liver-induced pulmonary vascular disorder with massive pulmonary microvascular dilation and excessive proliferation of pulmonary microvascular endothelial cells (PMVECs). Growing evidence suggests that autophagy is involved in pulmonary diseases, protectively or detrimentally. Thus, it is interesting and important to explore whether autophagy might be involved in and critical in HPS. In the present study, we report that autophagy was activated in common bile duct ligation (CBDL) rats and cultured pulmonary PMVECs induced by CBDL rat serum, two accepted in vivo and in vitro experimental models of HPS. Furthermore, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) significantly alleviated pathological alterations and typical symptom of HPS in CBDL rats in vivo, and consistently 3-MA significantly attenuated the CBDL rat serum-induced excessive proliferation of PMVECs in vitro. All these changes mediated by 3-MA might explain the observed prominent improvement of pulmonary appearance, edema, microvascular dilatation and arterial oxygenation in vivo. Collectively, these results suggest that autophagy activation may play a critical role in the pathogenesis of HPS, and autophagy inhibition may have a therapeutic potential for this disease. PMID:27480323

  20. Extract of Sesbania grandiflora Ameliorates Hyperglycemia in High Fat Diet-Streptozotocin Induced Experimental Diabetes Mellitus.

    Science.gov (United States)

    Panigrahi, Ghanshyam; Panda, Chhayakanta; Patra, Arjun

    2016-01-01

    Background. Sesbania grandiflora has been traditionally used as antidiabetic, antioxidant, antipyretic, and expectorant and in the management of various ailments. Materials and Methods. The study evaluates the antidiabetic activity of methanolic extract of Sesbania grandiflora (MESG) in type 2 diabetic rats induced by low dose streptozotocine and high fat diet. Diabetic rats were given vehicle, MESG (200 and 400 mg/kg, p.o.), and the standard drug, metformin (10 mg/kg), for 28 days. During the experimental period, body weight, abdominal girth, food intake, fasting serum glucose, urine analyses were measured. Insulin tolerance test was carried out on 25th day of drug treatment period. Serum analyses for lipid profile and SGOT and SGPT and serums creatinine, urea, protein, SOD, and MDA were also carried out. At the end of the experiment, animals were euthanized, the liver and pancreas were immediately dissected out, and the ratio of pancreas to body weight and hepatic glycogen were calculated. Results. MESG (200 and 400 mg/kg, p.o.) induced significant reduction (P < 0.05) of raised blood glucose levels in diabetic rats and also restored other parameters to normal level. Conclusion. Therefore, it is concluded that MESG has potential antihyperglycemic and antihyperlipemic activities and alleviate insulin resistance conditions. PMID:27313954

  1. A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia

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    Songqing Na

    2011-01-01

    Full Text Available Vitamin D receptor (VDR agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH2D3 and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia.

  2. Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Jin-Fang Zheng; Li-Jian Liang; Chang-Xiong Wu; Jin-Song Chen; Zhen-Sheng Zhang

    2006-01-01

    AIM: To investigate the effect of transplanted fetal liver epithelial progenitor (FLEP) cells on liver fibrosis in mice.METHODS: FLEP cells were isolated from embryonal day (ED) 14 BALB/c mice and transplanted into female syngenic BALB/c mice (n = 60). After partial hepatectomy (PH), diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN.Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN) in serum,and hydroxyproline (Hyp) content in liver were assessed.Alpha-smooth muscle actin (α-SMA) of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sry (sex determination region for Y chromosome) protein.RESULTS: Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and α-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo.CONCLUSION: Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.

  3. 5-Androstenediol Ameliorates Pleurisy, Septic Shock, and Experimental Autoimmune Encephalomyelitis in Mice

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    Ferdinando Nicoletti

    2010-01-01

    Full Text Available Androstenediol (androst-5-ene-3β,17β-diol; 5-AED, a natural adrenal steroid, has been shown to suppress experimental autoimmune encephalomyelitis (EAE in female SJL/J mice. We here report that 5-AED limits inflammation and proinflammatory cytokines including TNFα in murine models of carrageenan-induced pleurisy and lippopolysaccaride- (LPS induced septic shock. 5-AED binds to and transactivates sex steroid receptors with the same general rank order of potency (ERβ > ERα ≫ AR. 5-AED provides benefit in EAE in a dose-dependent fashion, even when treatment is delayed until onset of disease. The minimally effective dose may be as low as 4 mg/kg in mice. However, benefit was not observed when 5-AED was given in soluble formulation, leading to a short half-life and rapid clearance. These observations suggest that treatment with 5-AED limits the production of pro-inflammatory cytokines in these animal models and, ultimately, when formulated and administered properly, may be beneficial for patients with multiple sclerosis and other Th1-driven autoimmune diseases.

  4. Mechanical forces and lymphatic transport.

    Science.gov (United States)

    Breslin, Jerome W

    2014-11-01

    This review examines the current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect the pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. An improved understanding of the physiological mechanisms by which lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema. PMID:25107458

  5. Mechanical Forces and Lymphatic Transport

    Science.gov (United States)

    Breslin, Jerome W.

    2014-01-01

    This review examines current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including: evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. Improved understanding of the physiological mechanisms by lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema. PMID:25107458

  6. Eugenia jambolana Lam. Increases lifespan and ameliorates experimentally induced neurodegeneration in C. elegans

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    Maria de Fátima Bezerra

    2014-09-01

    Full Text Available Summary. Type-2 diabetes mellitus (T2DM, dyslipidemia (DL and inflammation (IF are associated with reduced lifespan (LS and increased risk of neurodegenerative diseases (NDG. Dysregulation in insulin/insulin-like growth factor-1 (IGF-1 (IIS signaling, forkhead box O transcription factor (FOXO and Silent Information Regulators or Sirtuins (SIRT may be responsible. We investigated the effect of spray dried Jambolan (Eugenia jambolana Lam. fruit in Caenorhabditis elegans model for lifespan, amyloid b1-42 (Ab1-42 aggregation induced paralysis and MPP+ (1-methyl-4-phenylpyridinium induced neurodegeneration. Effect on modulating critical genes involved signaling pathways important in IIS, LS and NDG were also studied in C. elegans. Results show suggest statistically significant increase in lifespan (9-22.7% coupled with a delay in Ab1-42 induced paralysis (11.5% and MPP+ induced paralysis (38-43%. Gene expression studies indicated a significant upregulation in expression of  C. elegans homologs of foxo, sirt1, dopamine D1 receptor and suggested a non-FOXO mediated mechanism of action.Industrial relevance. Jambolan is a bioactive-rich tropical fruit with high colorant potential. Despite this fact, its perishability has hampered its market and industrial use beyond the countries where it is cultivated. Considering that drying is a popular technique able to extend fruits shelf life and concentrate their natural bioactive compounds, this research investigates the health relevance of spray dried jambolan. Here we addressed the potential of dried Jambolan fruit to extend lifespan and inhibit the progression of experimentally induced neurodegeneration using the C. elegans model. We demonstrated that this convenient fruit product was able to increase the lifespan of C. elegans. The jambolan extracts also influenced some critical genes of signaling pathways relevant to metabolic diseases, aging and neurodegeneration. Based on our results, some insight about

  7. Amelioration of Experimental Autoimmune Encephalomyelitis by Plumbagin through Down-Regulation of JAK-STAT and NF-κB Signaling Pathways

    OpenAIRE

    Yan Jia; Ji Jing; Yang Bai; Zhen Li; Lande Liu; Jian Luo; Mingyao Liu; Huaqing Chen

    2011-01-01

    Plumbagin (PL), a herbal compound derived from roots of the medicinal plant Plumbago zeylanica, has been shown to have immunosuppressive properties. Present report describes that PL is a potent novel agent in control of encephalitogenic T cell responses and amelioration of mouse experimental autoimmune encephalomyelitis (EAE), through down-regulation of JAK-STAT pathway. PL was found to selectively inhibit IFN-γ and IL-17 production by CD4(+) T cells, which was mediated through abrogated phos...

  8. What Is the Lymphatic System?

    Science.gov (United States)

    ... archives // Knowledge and support What is the Lymphatic System? To better understand lymphedema , we first must understand the normal lymphatic system (see diagram) . This system functions parallel to the ...

  9. Infection of non-encapsulated species of Trichinella ameliorates experimental autoimmune encephalomyelitis involving suppression of Th17 and Th1 response.

    Science.gov (United States)

    Wu, Zhiliang; Nagano, Isao; Asano, Kazunobu; Takahashi, Yuzo

    2010-10-01

    Epidemiological and experimental studies have indicated that helminth infections can ameliorate autoimmune diseases. The present study investigated the amelioration effect of the Trichinella pseudospiralis infection on experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of central nervous system (CNS), and expression kinetics of Th17 and Th1 cytokine which play a crucial role in the pathogenesis of EAE. The results indicated that the infection of helminth T. pseudospiralis obviously ameliorated clinical severity and greatly delayed the onset of EAE induced by myelin oligodendrocyte glycoprotein (MOG) immunization. Infection caused much lesser inflammatory infiltration and demyilination in the CNS of infected EAE mice than uninfected EAE mice. The reduced infiltration was also suggested by the expressions of the inflammation cytokines, IL-17, IL-6, IL-1β, IFN-γ, and TNF-α, which were high in the spinal cords of the uninfected EAE mice, but was nearly normal or low in the infected EAE mice. The increased production of MOG-induced IL-17 and IFN-γ and the expression of IL-6, IL-1β, TGF-β in splenocytes after restimulation with MOG was inhibited in the infected EAE mice. On the other hand, the greatly induced Th2 response was observed in the splenocytes of the infected EAE mice. The present study showed that T. pseudospiralis infection can suppresses EAE by reducing the inflammatory infiltration in CNS, likely associated with the suppression of Th17 and Th1 responses by the infection. PMID:20661746

  10. ENDOMETRIOSIS WITH LYMPHATIC SPREAD

    Directory of Open Access Journals (Sweden)

    Narmadha

    2014-10-01

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

  11. Urban lymphatic filariasis

    DEFF Research Database (Denmark)

    Simonsen, Paul Erik; Mwakitalu, Mbutolwe E.

    2013-01-01

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

  12. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis

    Institute of Scientific and Technical Information of China (English)

    Kunwar; Shailubhai; Vaseem; Palejwala; Krishna; Priya; Arjunan; Sayali; Saykhedkar; Bradley; Nefsky; John; A; Foss; Stephen; Comiskey; Gary; S; Jacob; Scott; E; Plevy

    2015-01-01

    AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first

  13. Immunology of lymphatic filariasis

    OpenAIRE

    Babu, Subash; Nutman, Thomas B.

    2014-01-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen - specific Th2 response and an expansion of IL-10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen specific T cell hypo-responsiveness appears to be crucial for the maintenance of the sustained, long-stan...

  14. Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature

    OpenAIRE

    Chaitanya, Ganta Vijay; Omura, Seiichi; Sato, Fumitaka; Martinez, Nicholas E.; Minagar, Alireza; Ramanathan, Murali; Guttman, Bianca Weinstock; Zivadinov, Robert; Tsunoda, Ikuo; Alexander, Jonathan S

    2013-01-01

    Background Multiple sclerosis (MS) is associated with ectopic lymphoid follicle formation. Podoplanin+ (lymphatic marker) T helper17 (Th17) cells and B cell aggregates have been implicated in the formation of tertiary lymphoid organs (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium, we investigated whether the pathophysiology of MS involves inductions of lymphatic proteins in the infla...

  15. Immunology of lymphatic filariasis.

    Science.gov (United States)

    Babu, S; Nutman, T B

    2014-08-01

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

  16. Immunology of lymphatic filariasis

    Science.gov (United States)

    Babu, Subash; Nutman, Thomas B.

    2013-01-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen - specific Th2 response and an expansion of IL-10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen specific T cell hypo-responsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4+ T cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T cell hypo-responsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general. PMID:24134686

  17. Mesenchymal Stromal/Stem Cells Do Not Ameliorate Experimental Autoimmune Encephalomyelitis and Are Not Detectable in the Central Nervous System of Transplanted Mice.

    Science.gov (United States)

    Abramowski, Pierre; Krasemann, Susanne; Ernst, Thomas; Lange, Claudia; Ittrich, Harald; Schweizer, Michaela; Zander, Axel R; Martin, Roland; Fehse, Boris

    2016-08-01

    Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from different tissues. Based on their immunomodulatory and neuroprotective functions, MSC-based cell-therapy approaches have been suggested to antagonize inflammatory activity and neuronal damage associated with autoimmune disease of the central nervous system (CNS), for example, multiple sclerosis (MS). Intravenous MSC transplantation was reported to ameliorate experimental autoimmune encephalomyelitis (EAE), the murine model of MS, within days after transplantation. However, systemic distribution patterns and fate of MSCs after administration, especially their potential to migrate into inflammatory lesions within the CNS, remain to be elucidated. This question has of recent become particularly important, since therapeutic infusion of MSCs is now being tested in clinical trials with MS-affected patients. Here, we made use of the established EAE mouse model to investigate migration and therapeutic efficacy of murine bone marrow-derived MSCs. Applying a variety of techniques, including magnetic resonance imaging, immunohistochemistry, fluorescence in-situ hybridization, and quantitative polymerase chain reaction we found no evidence for immediate migration of infused MSC into the CNS of treated mice. Moreover, in contrast to other studies, transplanted MSCs did not ameliorate EAE. In conclusion, our data does not provide substantiation for a relevant migration of infused MSCs into the CNS of EAE mice supporting the hypothesis that potential therapeutic efficacy could be based on systemic effects. Evaluation of possible mechanisms underlying the observed discrepancies in MSC treatment outcomes between different EAE models demands further studies. PMID:27250994

  18. Trypanosoma cruzi-Trypanosoma rangeli co-infection ameliorates negative effects of single trypanosome infections in experimentally infected Rhodnius prolixus.

    Science.gov (United States)

    Peterson, Jennifer K; Graham, Andrea L; Elliott, Ryan J; Dobson, Andrew P; Triana Chávez, Omar

    2016-08-01

    Trypanosoma cruzi, causative agent of Chagas disease, co-infects its triatomine vector with its sister species Trypanosoma rangeli, which shares 60% of its antigens with T. cruzi. Additionally, T. rangeli has been observed to be pathogenic in some of its vector species. Although T. cruzi-T. rangeli co-infections are common, their effect on the vector has rarely been investigated. Therefore, we measured the fitness (survival and reproduction) of triatomine species Rhodnius prolixus infected with just T. cruzi, just T. rangeli, or both T. cruzi and T. rangeli. We found that survival (as estimated by survival probability and hazard ratios) was significantly different between treatments, with the T. cruzi treatment group having lower survival than the co-infected treatment. Reproduction and total fitness estimates in the T. cruzi and T. rangeli treatments were significantly lower than in the co-infected and control groups. The T. cruzi and T. rangeli treatment group fitness estimates were not significantly different from each other. Additionally, co-infected insects appeared to tolerate higher doses of parasites than insects with single-species infections. Our results suggest that T. cruzi-T. rangeli co-infection could ameliorate negative effects of single infections of either parasite on R. prolixus and potentially help it to tolerate higher parasite doses. PMID:27174360

  19. Initial afferent lymphatic vessels controlling outbound leukocyte traffic from skin to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Ignacio eMelero

    2013-12-01

    Full Text Available Tissue drains fluid and macromolecules through lymphatic vessels, which are lined by a specialized endothelium that expresses peculiar differentiation proteins, not found in blood vessels (i.e: LYVE-1, Podoplanin, PROX-1 and VEGFR-3. Lymphatic capillaries are characteristically devoid of a continuous basal membrane and are anchored to the ECM by elastic fibers that act as pulling ropes which open the vessel to avoid oedema if tissue volume increases, as it occurs upon inflammation. Lymphatic vessels are also crucial for the transit of T lymphocytes and antigen presenting cells from tissue to draining lymph nodes. Importantly, cell traffic control across lymphatic endothelium is differently regulated under resting and inflammatory conditions. Under steady-state non-inflammatory conditions, leukocytes enter into the lymphatic capillaries through basal membrane gaps (portals. This entrance is integrin-independent and seems to be mainly guided by CCL21 chemokine gradients acting on leukocytes expressing CCR7. In contrast, inflammatory processes in lymphatic capillaries involve a plethora of cytokines, chemokines, leukocyte integrins and other adhesion molecules. Importantly, under inflammation a role for integrins and their ligands becomes apparent and, as a consequence, the number of leukocytes entering the lymphatic capillaries multiplies several-fold. Enhancing transmigration of dendritic cells en route to lymph nodes is conceivably useful for vaccination and cancer immunotherapy, whereas interference with such key mechanisms may ameliorate autoimmunity or excessive inflammation. Recent findings illustrate how, transient cell-to-cell interactions between lymphatic endothelial cells and leukocytes contribute to shape the subsequent behaviour of leukocytes and condition the lymphatic vessel for subsequent trans-migratory events.

  20. Lymphatic Biodistribution of Polylactide Nanoparticles

    OpenAIRE

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

    2010-01-01

    Tumor metastases occur through both the cardiovascular and lymphatic circulations. However, the majority of nanoparticle biodistribution studies have been focused on the cardiovascular circulation. In this study, we report the formulation of Cy5-labeled polylactide (Cy5-PLA) nanoparticles with controlled size and surface features and the subsequent evaluation of their lymphatic biodistribution. Cy5-PLA nanoparticles were formulated through Cy5/(BDI)ZnN(TMS)2-mediated [(BDI) = 2-((2,6-diisopro...

  1. Lymphatic filariasis control in Tanzania

    DEFF Research Database (Denmark)

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

    2013-01-01

    Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with th...... with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania....

  2. Lymphatic Regulation of Cellular Trafficking

    Science.gov (United States)

    Jackson, David G.

    2016-01-01

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

  3. Ethyl pyruvate ameliorates experimental colitis in mice by inhibiting the HMGB1-Th17 and Th1/Tc1 responses.

    Science.gov (United States)

    Guo, Xianghua; Guo, Runhua; Luo, Xia; Zhou, Lian

    2015-12-01

    Ethyl pyruvate (EP), a simple lipophilic pyruvate ester, has demonstrated protective effects against murine colitis through inhibition the release of inflammatory factor high-mobility group protein box 1 (HMGB1). HMGB1 has been implicated in several autoimmune diseases by inducing Thl and Thl7 cells activation. This study was designed to investigate whether EP amelioration of murine colitis is related to the blocking of the HMGB1-Th17/Thl pathway. We induced murine colitis by intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Ethyl pyruvate was injected intraperitoneally once a day for 7days. One week after intrarectal challenge with TNBS, HMGB1, IL-17 and IFN-γ protein levels were remarkably increased following severe colon inflammation. Meanwhile, excessive infiltration of Th17 cells in colonic tissues, and an upregulated proportion of Th17 and Th1/Tc1 cells in the spleen and mesenteric lymph nodes (MLN) were found in the TNBS-treated group compared to the control group. Treatment with the HMGB1 inhibitor EP not only remarkably improved colon pathological damage, but also significantly reduced the number of Th17 cells in the local tissues of the colitis-induced mice. Furthermore, the percentage of Th1/Tc1 and Th17 cells in the spleen and MLN, as well as levels of serum IFN-γ and IL-17A, were all markedly decreased in the EP-treated group. Moreover, in vitro, our results showed that EP in a dose dependent manner inhibited HMGB1 release induced by LPS from CT26 cells (murine colon adenocarcinoma cell line). These results suggest that HMGB1 contributes to the development of murine colitis by promoting the Th17 and Th1/Tc1 responses, and that EP can significantly inhibit HMGB1-Th17 and Thl/Tc1 pathway activation, which may provide better protection to mice with TNBS-induced colitis.

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

    Science.gov (United States)

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

    2016-03-01

    The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum. PMID:26927910

  5. Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17.

    Science.gov (United States)

    Sun, Yan; Lin, Lian-Jie; Lin, Yan; Sang, Li-Xuan; Jiang, Min; Zheng, Chang-Qing

    2015-01-01

    This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).

  6. Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice.

    Science.gov (United States)

    Sun, Yafei; Tian, Tian; Gao, Juan; Liu, Xiaoqian; Hou, Huiqing; Cao, Runjing; Li, Bin; Quan, Moyuan; Guo, Li

    2016-03-15

    Immoderate immunoreaction of antigen-specific Th17 and Treg cell dysfunction play critical roles in the pathogenesis of multiple sclerosis. We examined Th17/Treg immune responses and the underlying mechanisms in response to metformin in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Metformin reduced Th17 and increased Treg cell percentages along with the levels of associated cytokines. Molecules involved in cellular metabolism were altered in mice with EAE. Suppressed activation of mTOR and its downstream target, HIF-1α, likely mediated the protective effects of metformin. Our findings demonstrate that regulation of T cell metabolism represents a new therapeutic target for CNS autoimmune disorders.

  7. Amelioration of experimental autoimmune encephalomyelitis by plumbagin through down-regulation of JAK-STAT and NF-κB signaling pathways.

    Directory of Open Access Journals (Sweden)

    Yan Jia

    Full Text Available Plumbagin (PL, a herbal compound derived from roots of the medicinal plant Plumbago zeylanica, has been shown to have immunosuppressive properties. Present report describes that PL is a potent novel agent in control of encephalitogenic T cell responses and amelioration of mouse experimental autoimmune encephalomyelitis (EAE, through down-regulation of JAK-STAT pathway. PL was found to selectively inhibit IFN-γ and IL-17 production by CD4(+ T cells, which was mediated through abrogated phosphorylation of JAK1 and JAK2. Consistent with IFN-γ and IL-17 reduction was suppressed STAT1/STAT4/T-bet pathway which is critical for Th1 differentiation, as well as STAT3/ROR pathway which is essential for Th17 differentiation. In addition, PL suppressed pro-inflammatory molecules such as iNOS, IFN-γ and IL-6, accompanied by inhibition of IκB degradation as well as NF-κB phosphorylation. These data give new insight into the novel immune regulatory mechanism of PL and highlight the great value of this kind of herb compounds in probing the complex cytokine signaling network and novel therapeutic targets for autoimmune diseases.

  8. Toll/Interleukin-1 Receptor Domain Derived from TcpC (TIR-TcpC) Ameliorates Experimental Autoimmune Arthritis by Down-modulating Th17 Cell Response.

    Science.gov (United States)

    Pasi, Shweta; Kant, Ravi; Surolia, Avadhesha

    2016-06-01

    Evasion through immunomodulation is one of the several strategies adopted by pathogens to prolong their survival within the host. One such pathogen, Escherichia coli CFT073, utilizes an immunomodulatory protein, TcpC, to combat the host's innate immune defense. TcpC abrogates the function of MyD88 in macrophages, thus perturbing all the signaling processes that involve this adaptor protein. Although central to various signaling pathways initiated by IL-1, IL-18, and toll-like receptors, the precise contribution of MyD88 to the development of autoimmunity, particularly rheumatoid arthritis, still needs extensive exploration. Herein, by using the toll/interleukin-1 receptor (TIR) domain homologous C-terminal motif of TcpC, i.e. TIR-TcpC, we found MyD88 to be critical for the induction and progression of rheumatoid arthritis through its pivotal role in the development of Th17 cells, the subset of CD4(+) T-cells widely implicated in various autoimmune disorders. The TIR-TcpC mediated inhibition of signaling through MyD88, and subsequent amelioration of experimental autoimmune arthritis was observed to be an outcome of perturbations in the NFκB-RORγt (RAR-related orphan receptor γt) axis. PMID:27022030

  9. Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

    Directory of Open Access Journals (Sweden)

    Shou-Chieh Wang

    2011-01-01

    Full Text Available Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glutathione activities significantly in diabetic kidney, and decreasing the plasma levels of triglyceride, low-density lipoprotein (LDL and increasing high-density lipoprotein (HDL value. In histological examination, HSE improves hyperglycemia-caused osmotic diuresis in renal proximal convoluted tubules (defined as hydropic change in diabetic rats. The study also reveals that up-regulation of Akt/Bad/14-3-3γ and NF-κB-mediated transcription might be involved. In conclusion, our results show that HSE possesses the potential effects to ameliorate diabetic nephropathy via improving oxidative status and regulating Akt/Bad/14-3-3γ signaling.

  10. Ameliorative effects of human adipose tissue-derived mesenchymal stem cells on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats

    Institute of Scientific and Technical Information of China (English)

    Myung-Soon Ko; Hyeong-geun Park; Young-Min Yun; Jeong Chan Ra; Taekyun Shin; Kyoung-Kap Lee

    2011-01-01

    Mesenchymal stem cells have been previously shown to exert an immunomodulatory function. The present study sought to investigate the effects of multipotential human adipose tissue-derived mesenchymal stem cells (hAdMSCs) on disease progression and cytokine expression in Lewis rats with experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein. The duration of EAE paralysis in the group treated on day 7 postimmunization with 5 × 106 hAdMSCs was significantly reduced compared with the vehicle-treated controls and the 1 × 106 hAdMSC- treated group. The duration of EAE paralysis in the groups treated with 5 × 106 hAdMSCs on both day 1 and day 7 postimmunization was significantly reduced compared with the vehicle-treated controls and the groups treated with 5 × 106 hAdMSCs on both day 7 and day 10 postimmunization. The mRNA expression of interleukin-10 and indoleamine 2, 3-dioxygenase was significantly decreased in the hAdMSC-treated group compared with the vehicle-treated group. These findings suggest that the ameliorative effects of hAdMSCs on EAE symptoms operate in a dose- and time-dependent manner and can be mediated in part by the ample production of anti-inflammatory cytokines.

  11. Lymphatic filariasis: Perspectives on lymphatic remodeling and contractile dysfunction in filarial disease pathogenesis

    OpenAIRE

    Chakraborty, Sanjukta; Gurusamy, Manokaran; Zawieja, David C.; Muthuchamy, Mariappan

    2013-01-01

    Lymphatic filariasis, one of the most debilitating diseases associated with the lymphatic system, affects over a hundred million people worldwide and manifests itself in a variety of severe clinical pathologies. The filarial parasites specifically target the lymphatics and impair lymph flow, which is critical for the normal functions of the lymphatic system in maintenance of body fluid balance and physiological interstitial fluid transport. The resultant contractile dysfunction of the lymphat...

  12. Amelioration of experimental colitis by Astragalus membranaceus through anti-oxidation and inhibition of adhesion molecule synthesis

    Institute of Scientific and Technical Information of China (English)

    Joshua Ka-Shun Ko; Flora Ying-Lee Lam; Andrew Pok-Lap Cheung

    2005-01-01

    AIM: To investigate the protective effects of Astragalus membranaceus(Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism.METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Rats were either pretreated with Am extract (2 or 4 g/kg, p.o. once daily) starting from 10 d before DNBS enema, or received Am post-treatment (2 or 4 g/kg, p.o.twice daily) on the three consecutive days following DNBS administration. Colonic lesion area and histological damage were determined, while the activities of myeloperoxidase (MPO) and xanthine oxidase, as well as reduced glutathione (GSH) content were measured in the excised colonic tissues. Besides, protein expression of inducible nitrite oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and P-selectin was also detected by Western blot analysis.RESULTS: Our findings had shown that both macroscopic lesion area and histological colonic damage induced by DNBS were significantly reduced by both Am pre- and post-treatments. These were accompanied by attenuation of the elevated colonic MPO activity and downregulation of the iNOS, P-selectin, and ICAM-1 protein expression.Besides, deprivation of colonic GSH level under colitis condition was also preserved.CONCLUSION: These results demonstrate that Am possesses both preventive and therapeutic potential in experimental colitis. The anti-inflammatory actions involve anti-oxidation along with inhibition of adhesion molecule synthesis in the colonic tissues.

  13. FTY720, Sphingosine 1-Phosphate Receptor Modulator, Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibition of T Cell Infiltration

    Institute of Scientific and Technical Information of China (English)

    Hirotoshi Kataoka; Kunio Sugahara; Kyoko Shimano; Koji Teshima; Mamoru Koyama; Atsushi Fukunari; Kenji Chiba

    2005-01-01

    FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P] on experimental autoimmune encephalomyelitis (EAE) in rats and mice.Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE,and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4+ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and (S)-FTY720-P. When FTY720 or (S)-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4+ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4+ T cells into the inflammation site.

  14. Prominent Lymphatic Vessel Hyperplasia with Progressive Dysfunction and Distinct Immune Cell Infiltration in Lymphedema.

    Science.gov (United States)

    Gousopoulos, Epameinondas; Proulx, Steven T; Scholl, Jeannette; Uecker, Maja; Detmar, Michael

    2016-08-01

    Lymphedema is a common complication that occurs after breast cancer treatment in up to 30% of the patients undergoing surgical lymph node excision. It is associated with tissue swelling, fibrosis, increased risk of infection, and impaired wound healing. Despite the pronounced clinical manifestations of the disease, little is known about the morphological and functional characteristics of the lymphatic vasculature during the course of lymphedema progression. We used an experimental murine tail lymphedema model where sustained fluid stasis was generated on disruption of lymphatic flow, resulting in chronic edema formation with fibrosis and adipose tissue deposition. Morphological analysis of the lymphatic vessels revealed a dramatic expansion during the course of the disease, with active proliferation of lymphatic endothelial cells at the early stages of lymphedema. The lymphatic capillaries exhibited progressively impaired tracer filling and retrograde flow near the surgery site, whereas the collecting lymphatic vessels showed a gradually decreasing contraction amplitude with unchanged contraction frequency, leading to lymphatic contraction arrest at the later stages of the disease. Lymphedema onset was associated with pronounced infiltration by immune cells, predominantly Ly6G(+) and CD4(+) cells, which have been linked to impaired lymphatic vessel function. PMID:27315777

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-27

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

  16. Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling.

    Science.gov (United States)

    Li, Wen; Zhang, Zhihui; Zhang, Kai; Xue, Zhenyi; Li, Yan; Zhang, Zimu; Zhang, Lijuan; Gu, Chao; Zhang, Qi; Hao, Junwei; Da, Yurong; Yao, Zhi; Kong, Ying; Zhang, Rongxin

    2016-10-01

    Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.

  17. Lymphatic Filariasis control in Tanzania

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  18. Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

    Directory of Open Access Journals (Sweden)

    Vikash Chandra

    Full Text Available BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs to differentiate into functional islet like cell aggregates (ICAs. Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17 and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes.

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

    Science.gov (United States)

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

    2015-12-01

    Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over-activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation. PMID:26546103

  20. Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

    Institute of Scientific and Technical Information of China (English)

    Li-Fei; Yuan; Guang-Da; Li; Xin-Jun; Ren; Hong; Nian; Xiao-Rong; Li; Xiao-Min; Zhang

    2015-01-01

    · AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

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

    Directory of Open Access Journals (Sweden)

    Hiroo Suami

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

  2. Seroprevalence of lymphatic filariasis at Puducherry

    OpenAIRE

    S.C. Parija; Garg, Atul

    2010-01-01

    Lymphatic filariasis is a major vector borne disease prevalent in the tropics. This study was carried out to estimate the seroprevalence of lymphatic filariasis in and around Puducherry using indirect haemaggulutination test. Of the 5056 clinically suspected cases, 2214 (43.78%) were found to be positive, of whom majority were males (57.8%) belonging to the age group of 21–40 years, indicating that lymphatic filariasis mainly affects the adolescents and adults mainly. This high seroprevalence...

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

    Science.gov (United States)

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

    2014-03-01

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

  4. Lymphatics and Lymphangiogenesis in the Eye

    Directory of Open Access Journals (Sweden)

    Shintaro Nakao

    2012-01-01

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

  5. Abnormal lung lymphatics and respiratory failure.

    OpenAIRE

    Moss, S F; Currie, D C; Sheffield, E A; M. Baxter; Corrin, B.; Evans, T. W.

    1989-01-01

    A 65 year old man presented with respiratory failure, pleural effusions, fine reticulonodular shadowing on a chest radiograph, and severe impairment of carbon monoxide diffusing capacity (transfer factor). Open lung biopsy showed only dilated pleural and subpleural lymphatic channels. Hypoplastic deep pulmonary lymphatics may have led to respiratory failure.

  6. Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Souheil El-Chemaly

    2012-09-01

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

  7. Lymphatic Territories (Lymphosomes) in a Canine: An Animal Model for Investigation of Postoperative Lymphatic Alterations

    OpenAIRE

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

    2013-01-01

    Background Lymph node dissection is often performed as a part of surgical treatment for breast cancer and malignant melanoma to prevent malignant cells from traveling via the lymphatic system. Currently little is known about postoperative lymphatic drainage pattern alterations. This knowledge may be useful for management of recurrent cancer and prevention of breast cancer related lymphedema. We mapped the complete superficial lymphatic system of a dog and used this canine model to perform pre...

  8. Elimination of Lymphatic Filariasis in Southern India

    OpenAIRE

    Sanjay Pattanshetty; Ashwini Kumar; Ravi Kumar; Rao, Chythra R.; Sanjeev Badiger; Rashmi R; Sneha Kamath

    2010-01-01

    BackgroundLymphatic filariasis is an important public health problem in India. Inspite of National filarial control programme (NFCP) being in place for lymphatic filariasis (LF) elimination, several important issues need to be addressed. There is uncertainty about the coverage and compliance to treatment in order to achieve elimination. Method A community based cross-sectional study was conducted as per the National Vector Borne Disease Control Programme (NVBDCP) directions. The study includ...

  9. Murine CD4+CD25- cells activated in vitro with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis in vivo

    Directory of Open Access Journals (Sweden)

    Majowicz Anna

    2012-12-01

    Full Text Available Abstract Background Induced regulatory T (iTreg lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore new techniques to generate iTreg cells and to determine their physiological relevance. Methods Using phorbol myristate acetate (PMA/ionomycin and anti-CD3 activation of CD4+CD25- cells we generated in vitro functional CD4+CD25+ iTreg (TregPMA cells. Functionality of the generated TregPMA cells was tested in vivo in a mouse model of inflammatory bowel disease (IBD - CD45RB transfer colitis model. Results TregPMA cells expressed regulatory markers and proved to ameliorate the disease phenotype in murine CD45RB transfer colitis model. The body weight loss and disease activity scores for TregPMA treated mice were reduced when compared to diseased control group. Histological assessment of colon sections confirmed amelioration of the disease phenotype. Additionally, cytokine analysis showed decreased levels of proinflammatory colonic and plasma IL-6, colonic IL-1 β and higher levels of colonic IL-17 when compared to diseased control group. Conclusions This study identifies a new method to generate in vitro iTreg cells (TregPMA cells which physiological efficacy has been demonstrated in vivo.

  10. Advances in Lymphatic Imaging and Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-10

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

  11. Platelets: covert regulators of lymphatic development.

    Science.gov (United States)

    Bertozzi, Cara C; Hess, Paul R; Kahn, Mark L

    2010-12-01

    The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology. PMID:21071706

  12. Comparative and Developmental Anatomy of Cardiac Lymphatics

    Directory of Open Access Journals (Sweden)

    A. Ratajska

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tan Truong

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

  14. Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model.

    Science.gov (United States)

    Souza, Éricka L; Elian, Samir D; Paula, Laís M; Garcia, Cristiana C; Vieira, Angélica T; Teixeira, Mauro M; Arantes, Rosa M; Nicoli, Jacques R; Martins, Flaviano S

    2016-03-01

    Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the gut that include ulcerative colitis and Crohn's disease. Probiotics are live micro-organisms that may be used as adjuvant therapy for patients with IBD. The aim of this study was to evaluate the effect of prophylactic ingestion of Escherichia coli strain Nissle 1917 (EcN) in a murine model of colitis. For induction of colitis, mice were given a 3.5% dextran sodium sulfate (DSS) solution for 7 days in drinking water. EcN administration to mice subjected to DSS-induced colitis resulted in significant reduction in clinical and histopathological signs of disease and preservation of intestinal permeability. We observed reduced inflammation, as assessed by reduced levels of neutrophils, eosinophils, chemokines and cytokines. We observed an increase in the number of regulatory T-cells in Peyer's patches. Germ-free mice received faecal content from control or EcN-treated mice and were then subjected to DSS-induced colitis. We observed protection from colitis in animals that were colonized with faecal content from EcN-treated mice. These results suggest that preventative oral administration of EcN or faecal microbiota transplantation with EcN-containing microbiota ameliorates DSS-induced colitis by modifying inflammatory responsiveness to DSS.

  15. Activation of aryl hydrocarbon receptor (AhR leads to reciprocal epigenetic regulation of FoxP3 and IL-17 expression and amelioration of experimental colitis.

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    Narendra P Singh

    Full Text Available BACKGROUND: Aryl hydrocarbon receptor (AhR, a transcription factor of the bHLH/PAS family, is well characterized to regulate the biochemical and toxic effects of environmental chemicals. More recently, AhR activation has been shown to regulate the differentiation of Foxp3(+ Tregs as well as Th17 cells. However, the precise mechanisms are unclear. In the current study, we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AhR ligand, on epigenetic regulation leading to altered Treg/Th17 differentiation, and consequent suppression of colitis. METHODOLOGY/PRINCIPAL FINDINGS: Dextran sodium sulphate (DSS administration induced acute colitis in C57BL/6 mice, as shown by significant weight loss, shortening of colon, mucosal ulceration, and increased presence of CXCR3(+ T cells as well as inflammatory cytokines. Interestingly, a single dose of TCDD (25 µg/kg body weight was able to attenuate all of the clinical and inflammatory markers of colitis. Analysis of T cells in the lamina propria (LP and mesenteric lymph nodes (MLN, during colitis, revealed decreased presence of Tregs and increased induction of Th17 cells, which was reversed following TCDD treatment. Activation of T cells from AhR(+/+ but not AhR (-/- mice, in the presence of TCDD, promoted increased differentiation of Tregs while inhibiting Th17 cells. Analysis of MLN or LP cells during colitis revealed increased methylation of CpG islands of Foxp3 and demethylation of IL-17 promoters, which was reversed following TCDD treatment. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate for the first time that AhR activation promotes epigenetic regulation thereby influencing reciprocal differentiation of Tregs and Th17 cells, and amelioration of inflammation.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  17. [Lymphatic malformations in the head and neck area].

    Science.gov (United States)

    Wiegand, S; Werner, J A

    2016-02-01

    Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies. PMID:26820157

  18. Lymphatic spreading and lymphadenectomy for esophagealcarcinoma

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Esophageal carcinoma (EC) is a highly lethal malignancywith a poor prognosis. One of the most importantprognostic factors in EC is lymph node status. Therefore,lymphadenectomy has been recognized as a keythat influences the outcome of surgical treatment forEC. However, the lymphatic drainage system of theesophagus, including an abundant lymph-capillarynetwork in the lamina propria and muscularis mucosa, isvery complex with cervical, mediastinal and celiac nodespreading. The extent of lymphadenectomy for EC hasalways been controversial because of the very complexpattern of lymph node spreading. In this article,published literature regarding lymphatic spreading wasreviewed and the current lymphadenectomy trends forEC are discussed.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections...... 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......-induced vascular relaxation, which led to blood perfusion into the lymphatic system. NO blockage almost completely abrogated hypoxia-induced ALC relaxation and lymphatic perfusion. These findings uncover mechanisms underlying hypoxia-induced oxygen compensation by perfusion of existing lymphatics in fish. Our...

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

    Science.gov (United States)

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

    2016-09-01

    An adolescent with plastic bronchitis due to congenital heart disease had altered mental status after an interventional lymphatic procedure in which lipiodol contrast was used. Neuroimaging revealed cerebral lipiodol embolization due to direct shunting between lymphatic channels and pulmonary veins. Cerebral lipiodol embolization is a potential neurologic morbidity associated with interventional lymphatic procedures. PMID:27297208

  1. Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice.

    Science.gov (United States)

    Ozgun-Acar, Ozden; Celik-Turgut, Gurbet; Gazioglu, Isil; Kolak, Ufuk; Ozbal, Seda; Ergur, Bekir U; Arslan, Sevki; Sen, Alaattin; Topcu, Gulacti

    2016-09-15

    expression profiling of the transcriptome revealed that COWE treatment caused the down regulation of a group of genes involved in the immune response, inflammatory response, antigen processing and presentation, B-cell-mediated immunity and innate immune response. Collectively, these results suggest anti-neuroinflammatory mechanisms by which COWE treatment delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs. PMID:27609283

  2. 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

  3. Modelling Lymphatic Filariasis: Transmission and Control

    NARCIS (Netherlands)

    S. Swaminathan

    2004-01-01

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

  4. Lymphatic filariasis control in Tanga Region, Tanzania

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. 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.

  6. Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development

    Directory of Open Access Journals (Sweden)

    Baptiste Coxam

    2014-05-01

    Full Text Available Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhesion, mixing, regression, and shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1, with reduced lymphatic vessel development. A mutation in polycystic kidney disease 1a was responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD. Initial lymphatic precursor sprouting is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice has no effect on precursor sprouting but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation, and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development.

  7. Aqueous Extract from Hibiscus sabdariffa Linnaeus Ameliorate Diabetic Nephropathy via Regulating Oxidative Status and Akt/Bad/14-3-3γ in an Experimental Animal Model

    OpenAIRE

    Wen-Chin Lee; Huei-Jane Lee; Chao-Hsin Lee; Chau-Jong Wang; Shiow-Fen Lee; Shou-Chieh Wang

    2011-01-01

    Several studies point out that oxidative stress maybe a major culprit in diabetic nephropathy. Aqueous extract of Hibiscus sabdariffa L. (HSE) has been demonstrated as having beneficial effects on anti-oxidation and lipid-lowering in experimental studies. This study aimed at investigating the effects of Hibiscus sabdariffa L. on diabetic nephropathy in streptozotocin induced type 1 diabetic rats. Our results show that HSE is capable of reducing lipid peroxidation, increasing catalase and glut...

  8. Vitamin D3 and Monomethyl Fumarate Enhance Natural Killer Cell Lysis of Dendritic Cells and Ameliorate the Clinical Score in Mice Suffering from Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Zaidoon Al-Jaderi

    2015-11-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a CD4+ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139–151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D3 (vitamin D3, or with monomethyl fumarate (MMF was then examined. We observed that both vitamin D3 and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK cells from vitamin D3-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS is to enhance NK cell lysis of dendritic cells.

  9. Vitamin D₃ and monomethyl fumarate enhance natural killer cell lysis of dendritic cells and ameliorate the clinical score in mice suffering from experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Al-Jaderi, Zaidoon; Maghazachi, Azzam A

    2015-11-01

    Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139-151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells. PMID:26580651

  10. Suppression of NF-κB signaling and NLRP3 inflammasome activation in macrophages is responsible for the amelioration of experimental murine colitis by the natural compound fraxinellone

    International Nuclear Information System (INIS)

    Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b+ macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1β and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation. - Highlights: • Fraxinellone, a lactone compound, alleviated DSS induced colitis. • The effects of fraxinellone were attributed to its inhibition on infiltrated

  11. Integration des sciences et de la langue: Creation et experimentation d'un modele pedagogique pour ameliorer l'apprentissage des sciences en milieu francophone minoritaire

    Science.gov (United States)

    Cormier, Marianne

    Les faibles resultats en sciences des eleves du milieu francophone minoritaire, lors d'epreuves au plan national et international, ont interpelle la recherche de solutions. Cette these avait pour but de creer et d'experimenter un modele pedagogique pour l'enseignement des sciences en milieu linguistique minoritaire. En raison de la presence de divers degres de francite chez la clientele scolaire de ce milieu, plusieurs elements langagiers (l'ecriture, la discussion et la lecture) ont ete integres a l'apprentissage scientifique. Nous avions recommande de commencer le processus d'apprentissage avec des elements langagiers plutot informels (redaction dans un journal, discussions en dyades...) pour progresser vers des activites langagieres plus formelles (redaction de rapports ou d'explications scientifiques). En ce qui a trait a l'apprentissage scientifique, le modele preconisait une demarche d'evolution conceptuelle d'inspiration socio-constructiviste tout en s'appuyant fortement sur l'apprentissage experientiel. Lors de l'experimentation du modele, nous voulions savoir si celui-ci provoquait une evolution conceptuelle chez les eleves, et si, simultanement, le vocabulaire scientifique de ces derniers s'enrichissait. Par ailleurs, nous cherchions a comprendre comment les eleves vivaient leurs apprentissages dans le cadre de ce modele pedagogique. Une classe de cinquieme annee de l'ecole de Grande-Digue, dans le Sud-est du Nouveau-Brunswick, a participe a la mise a l'essai du modele en etudiant les marais sales locaux. Lors d'entrevues initiales, nous avons remarque que les connaissances des eleves au sujet des marais sales etaient limitees. En effet, s'ils etaient conscients que les marais etaient des lieux naturels, ils ne pouvaient pas necessairement les decrire avec precision. Nous avons egalement constate que les eleves utilisaient surtout des mots communs (plantes, oiseaux, insectes) pour decrire le marais. Les resultats obtenus indiquent que les eleves ont

  12. Suppression of NF-κB signaling and NLRP3 inflammasome activation in macrophages is responsible for the amelioration of experimental murine colitis by the natural compound fraxinellone

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xue-Feng; Ouyang, Zi-Jun; Feng, Li-Li; Chen, Gong; Guo, Wen-Jie; Shen, Yan; Wu, Xu-Dong; Sun, Yang, E-mail: yangsun@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

    2014-11-15

    Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b{sup +} macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1β and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation. - Highlights: • Fraxinellone, a lactone compound, alleviated DSS induced colitis. • The effects of fraxinellone were attributed to its inhibition on

  13. Rosmarinus officinalis L. extract ameliorates intestinal inflammation through MAPKs/NF-κB signaling in a murine model of acute experimental colitis.

    Science.gov (United States)

    Medicherla, Kanakaraju; Ketkar, Avanee; Sahu, Bidya Dhar; Sudhakar, Godi; Sistla, Ramakrishna

    2016-07-13

    We investigated the anti-inflammatory and anti-colitis effects of Rosmarinus officinalis L. extract (RE) by using both in vitro LPS-activated mouse RAW 264.7 macrophages and in vivo dextran sulfate sodium (DSS)-induced experimental murine colitis and suggested the underlying possible mechanisms. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was performed to identify the major components present in the RE. The clinical signs, biochemistry, immunoblot, ELISA and histology in colon tissues were assessed in order to elucidate the beneficial effect of RE. RE suppressed the LPS-induced pro-inflammatory cytokine production and the expressions of inflammatory proteins in macrophages. Administration of RE (50 and 100 mg kg(-1)) also significantly reduced the severity of DSS-induced murine colitis, as assessed by the clinical symptoms, colon length and histology. RE administration prevented the DSS-induced activation of p38, ERK and JNK MAPKs, attenuated IκBα phosphorylation and subsequent nuclear translocation and DNA binding of NF-κB (p65). RE also suppressed the COX-2 and iNOS expressions, decreased the levels of TNF-α and IL-6 cytokines and the myeloperoxidase activity in the colon tissue. Histological observation revealed that RE administration alleviated mucosal damage and inflammatory cell infiltration induced by DSS in the colon tissue. Hence, RE could be used as a new preventive and therapeutic food ingredient or as a dietary supplement for inflammatory bowel disease. PMID:27349640

  14. Elimination of lymphatic filariasis in the Gambia.

    OpenAIRE

    Rebollo, Maria P.; Sana Malang Sambou; Brent Thomas; Nana-Kwadwo Biritwum; Momodou C Jaye; Louise Kelly-Hope; Alba Gonzalez Escalada; Molyneux, David H; Bockarie, Moses J.

    2015-01-01

    Background The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF) in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA). The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interr...

  15. Lymphatic Filariasis Disseminating to the Upper Extremity

    OpenAIRE

    Catherine Maldjian; Vineet Khanna; Bevan Tandon; Matthew Then; Mohamed Yassin; Richard Adam; Klein, Michael J.

    2014-01-01

    Lymphatic filariasis is the most common cause of acquired lymphedema worldwide (Szuba and Rockson, 1998). It is endemic to tropical and subtropical regions, and its effects are devastating. With over 100 million infected persons, it ranks second only to leprosy as the leading cause of permanent and long-term disability. Wuchereria bancrofti is the etiologic agent in 90% of cases. There is a dearth of published MRI findings with pathologically proven active infections, making this entity even ...

  16. Lymphatic filariasis: A view at pathological diversity

    OpenAIRE

    Mahalingashetti, Prashant Basavaraj; Subramanian, Ramaswamy Anikode; Jayker, Sushan Shweta; A.vijay

    2014-01-01

    Filariasis is traditionally diagnosed following screening of peripheral smear for microfilaria. Clinically lymphatic filariasis mimics the common local diseases. Thus, it is plausible to observe this parasitic infection in histological sections. We encountered three such cases, which displayed diverse patterns of immune response. Presence of both dead and viable worm at the same foci suggests that such immune response could be the result of parasitic death. Histological features such as endot...

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

    Science.gov (United States)

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

    2012-06-14

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

  18. ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile.

    Directory of Open Access Journals (Sweden)

    Rie Yamamoto

    Full Text Available Sphingosine-1-phosphate (S1P is a biologically active sphingolipid that acts through the members of a family of five G protein-coupled receptors (S1P1-S1P5. S1P1 is a major regulator of lymphocyte trafficking, and fingolimod, whose active metabolite fingolimod phosphate acts as a nonselective S1P receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating the lymphocyte trafficking by inducing down regulation of lymphocyte S1P1. Here, we detail the pharmacological profile of 5-{5-[3-(trifluoromethyl-4-{[(2S-1,1,1-trifluoropropan-2-yl]oxy}phenyl]-1,2,4-oxadiazol-3-yl}-1H-benzimidazole (ASP4058, a novel next-generation S1P receptor agonist selective for S1P1 and S1P5. ASP4058 preferentially activates S1P1 and S1P5 compared with S1P2, 3, 4 in GTPγS binding assays in vitro. Oral administration of ASP4058 reduced the number of peripheral lymphocytes and inhibited the development of experimental autoimmune encephalomyelitis (EAE in Lewis rats. Further, ASP4058 prevented relapse of disease in a mouse model of relapsing-remitting EAE. Although these immunomodulatory effects were comparable to those of fingolimod, ASP4058 showed a wider safety margin than fingolimod for bradycardia and bronchoconstriction in rodents. These observations suggest that ASP4058 represents a new therapeutic option for treating multiple sclerosis that is safer than nonselective S1P receptor agonists such as fingolimod.

  19. Lymphatic Filariasis Disseminating to the Upper Extremity

    Directory of Open Access Journals (Sweden)

    Catherine Maldjian

    2014-01-01

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

  20. Lymphatic Filariasis Disseminating to the Upper Extremity

    Science.gov (United States)

    Maldjian, Catherine; Khanna, Vineet; Tandon, Bevan; Then, Matthew; Yassin, Mohamed; Adam, Richard; Klein, Michael J.

    2014-01-01

    Lymphatic filariasis is the most common cause of acquired lymphedema worldwide (Szuba and Rockson, 1998). It is endemic to tropical and subtropical regions, and its effects are devastating. With over 100 million infected persons, it ranks second only to leprosy as the leading cause of permanent and long-term disability. Wuchereria bancrofti is the etiologic agent in 90% of cases. There is a dearth of published MRI findings with pathologically proven active infections, making this entity even more of a diagnostic dilemma. Imaging may provide the first clue that one is dealing with a parasite and may facilitate proper treatment and containment of this disease. This is the first report of pathologic correlation with MRI findings in the extremity in active filariasis. The magnetic resonance images demonstrate an enhancing, infiltrative, mass-like appearance with partial encasement of vasculature that has not been previously described in filariasis. Low signal strands in T2-hyperintense dilated lymphatic channels are seen and may depict live adult worms. We hypothesize that the low signal strands correspond to the collagen rich acellular cuticle. This, in combination with the surrounding hyperintense T2 signal, corresponding to a dilated lymphatic channel, may provide more specific MRI findings for active nematodal infection, which can prompt early biopsy, pathological correlation, and diagnosis. PMID:24707427

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

    OpenAIRE

    Nutman, Thomas B.

    2013-01-01

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

  2. New developments in clinical aspects of lymphatic disease

    OpenAIRE

    Mortimer, Peter S.; Stanley G Rockson

    2014-01-01

    The lymphatic system is fundamentally important to cardiovascular disease, infection and immunity, cancer, and probably obesity — the four major challenges in healthcare in the 21st century. This Review will consider the manner in which new knowledge of lymphatic genes and molecular mechanisms has demonstrated that lymphatic dysfunction should no longer be considered a passive bystander in disease but rather an active player in many pathological processes and, therefore, a genuine target for ...

  3. [Mediastinal lymphatic spread of bronchopulmonary cancer].

    Science.gov (United States)

    Riquet, M

    1991-01-01

    The mediastinum may be divided into 4 zones divided by the tracheo-bronchial axis in which are situated the lymphatic chains involved in the lymphatic drainage of the lungs. In the upper right zone there are 2 chains which are frequently involved, the right paratracheal chain (PTD) and the tracho-oesophageal chain (TO) and 2 lymphatic chains which are less often involved, the superior right phrenic chain (PH Dt) and the lymphatic chain which crosses the Azygos vein (AZM). In the superior left zone are found 2 chains which are frequently infiltrated: The pre-aortic carotid chain (AO) and the left superior bronchial chain (BSG) and 2 chains which are more rarely involved: The left superior phrenic (PHG) and the chain which crosses the aorta (the minor aorta Azygos; AOmi). At the level of the right and left inferior zones are found important groups of lymphatic ganglia at the intratracheo-bronchial bifurcation (ITB) and of one other part of the tracheo-oesophageal axis, the juxta-oesophageal ganglia (OE) and those of the triangular ligament (LT). The lymph coming from the pulmonary segments crosses the ganglia (LN) of the segments of the lobe and of the hilum before reaching the mediastinum and then at the final stage the lymph nodes situated on the margins of the mediastinum considered as N3 in cancer assessment. This schema is not the rule. In less than 5% of cases the lymph may drain without any lymph node relay either to the subclavicular hollow or to the thoracic duct in the mediastinum. More frequently (in 20-35% cases according to the segment considered) the lymph returns directly to the mediastinum ganglia without relaying through the intrapulmonary ganglia. Finally there are those cases where only the perilobar LN are involved. In these cases it is not necessarily the LN of the lobe drained but sometimes of another pulmonary lobe. These direct paths (N2) confirmed in study of cancer, demand and justify the need for a systematic cure of mediastinal LN. It is

  4. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung.

    Science.gov (United States)

    Zhang, Xuefeng; Jiang, Susan; Yu, Jinlong; Kuzontkoski, Paula M; Groopman, Jerome E

    2015-08-01

    Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure increased fibronectin (FN) expression, decreased Robo4 expression, and enhanced the permeability of L-LEC monolayers. Moreover, incubating L-LECs with both cocaine and HIV-1 gp120 exacerbated hyperpermeability, significantly enhanced apoptosis, and further impaired in vitro wound healing as compared with cocaine alone. Our studies also suggested that the sigma-1 receptor (Sigma-1R) and the dopamine-4 receptor (D4R) are involved in cocaine-induced pathology in L-LECs. Seeking clinical correlation, we found that FN levels in sera and lung tissue of HIV(+) donors were significantly elevated as compared to HIV(-) donors. Our in vitro data demonstrate that cocaine and HIV-1 gp120 induce dysfunction and damage of lung lymphatics, and suggest that cocaine use may exacerbate pulmonary edema and fibrosis associated with HIV infection. Continued exploration of the interplay between cocaine and HIV should assist the design of therapeutics to ameliorate HIV-induced pulmonary disorders within the drug using population. PMID:26311830

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

    NARCIS (Netherlands)

    Clarijs, Johannes Antonius Godefridus Marinus

    2003-01-01

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

  6. Lymphatic drainage and CTV in pancreatic carcinoma.

    Science.gov (United States)

    Morganti, Alessio G; Cellini, Numa; Mattiucci, Gian Carlo; Macchia, Gabriella; Smaniotto, Daniela; Luzi, Stefano; Balducci, Mario; Deodato, Francesco; Valentini, Vincenzo; Trodella, Lucio

    2003-01-01

    CTV definition in exclusive or adjuvant radiation therapy of pancreatic carcinoma is essentially based on the opinion of "expert" authors and on the knowledge of lymphatic pathways. The subject has been widely debated. Radiotherapy treatments of the entire upper abdomen (liver and pancreatic region), pancreas and lymph node stations, to volumes focused on macroscopic tumor only, have been proposed. Carcinoma of exocrine pancreas is characterized by the frequent, early appearance of metastasis via the lymphatic route. Most commonly involved lymph node stations include those of the celiac trunk, superior mesenteric, peripancreatic, lumboaortic lymph nodes, those of the hepatic portal (the latter in particular for pancreatic head tumors) and of the hilum of spleen (the latter in particular for pancreatic tail tumors). The possible multicentricity of pancreatic carcinoma, most likely due to intraductal spread, should lead to the inclusion in the CTV of the entire pancreatic parenchyma. This should be considered also for the frequent perineural intra- or extrapancreatic spread of pancreatic carcinoma present also in small tumors (T1). In extrapancreatic spread the retropancreatic adipose tissue should be included in the CTV at least at the GTV level. At the present state of knowledge, in the absence of pattern of failure analysis and of comparison of different treatment approaches, in terms of the definition of volumes of interest, CTV definitions which include lymphatic drainage stations, most part of pancreatic parenchyma and retropancreatic adipose tissue seem justified especially in treatments for cure. In palliation, the CTV may be limited to the GTV and the adipose tissue behind it. PMID:15018319

  7. Lymphatic filariasis: A view at pathological diversity

    Science.gov (United States)

    Mahalingashetti, Prashant Basavaraj; Subramanian, Ramaswamy Anikode; Jayker, Sushan Shweta; Vijay, A

    2014-01-01

    Filariasis is traditionally diagnosed following screening of peripheral smear for microfilaria. Clinically lymphatic filariasis mimics the common local diseases. Thus, it is plausible to observe this parasitic infection in histological sections. We encountered three such cases, which displayed diverse patterns of immune response. Presence of both dead and viable worm at the same foci suggests that such immune response could be the result of parasitic death. Histological features such as endothelial injury and granulomatous response attests to the role of Wolbachia bacteria in influencing tissue response. PMID:25250237

  8. Lymphatic Filariasis in Children in Haiti.

    Science.gov (United States)

    Byrne, Sharon K; Collins, Shonta D

    2015-01-01

    Using available evidence and astute assessment skills, nurses and advanced practice nurses, as members of an inter-professional team, were able to assess, diagnose, and initiate treatment for a child with lymphatic filariasis within a global health practice setting. The lessons learned during health outreach trips to an underserved commune of Port-au-Prince, Haiti can promote an understanding of appropriate nursing practice related to this parasitic infection. They can also assist nursing students, nurse practitioner students, and faculties as members of a medical outreach team to promote sustainability which is a benchmark of nursing leadership in global health. PMID:26121754

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

    NARCIS (Netherlands)

    Schulte-Merker, S.; Sabine, A.; Petrova, T.V.

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. How Do Meningeal Lymphatic Vessels Drain the CNS?

    Science.gov (United States)

    Raper, Daniel; Louveau, Antoine; Kipnis, Jonathan

    2016-09-01

    The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow. PMID:27460561

  12. Elimination of Lymphatic Filariasis in Southern India

    Directory of Open Access Journals (Sweden)

    Sanjay Pattanshetty

    2010-12-01

    Full Text Available BackgroundLymphatic filariasis is an important public health problem in India. Inspite of National filarial control programme (NFCP being in place for lymphatic filariasis (LF elimination, several important issues need to be addressed. There is uncertainty about the coverage and compliance to treatment in order to achieve elimination. Method A community based cross-sectional study was conducted as per the National Vector Borne Disease Control Programme (NVBDCP directions. The study included survey of 200 households of Dakshina Kannada District, South India where the Mass drug administration (MDA program was conducted. The main objective of the study was to assess the coverage and compliance to MDA. ResultsOut of the total 1050 eligible people, 876 (83% received the DEC tablets; so, the coverage was 83%. Among those who received the tablets, only 777 (88.7% received the adequate dose and only 670 (76.8% people actually consumed the tablets. Hence, compliance rate was only 76.8%.ConclusionThe planning and implementation of MDA programme needs to be strengthened by efficient micro planning, inter sectoral co-ordination and motivating the community to participate in the MDA programme.

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

    Science.gov (United States)

    Kurtz, Kristine H; Souza-Smith, Flavia M; Moor, Andrea N; Breslin, Jerome W

    2014-01-01

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

  14. Rho Kinase Enhances Contractions of Rat Mesenteric Collecting Lymphatics

    Science.gov (United States)

    Kurtz, Kristine H.; Souza-Smith, Flavia M.; Moor, Andrea N.; Breslin, Jerome W.

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kristine H Kurtz

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-07-15

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

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

    Science.gov (United States)

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

    2016-09-01

    Lymphatic remodeling in tumor microenvironments correlates with progression and metastasis, and local lymphatic vessels play complex and poorly understood roles in tumor immunity. Tumor lymphangiogenesis is associated with increased immune suppression, yet lymphatic vessels are required for fluid drainage and immune cell trafficking to lymph nodes, where adaptive immune responses are mounted. Here, we examined the contribution of lymphatic drainage to tumor inflammation and immunity using a mouse model that lacks dermal lymphatic vessels (K14-VEGFR3-Ig mice). Melanomas implanted in these mice grew robustly, but exhibited drastically reduced cytokine expression and leukocyte infiltration compared with those implanted in control animals. In the absence of local immune suppression, transferred cytotoxic T cells more effectively controlled tumors in K14-VEGFR3-Ig mice than in control mice. Furthermore, gene expression analysis of human melanoma samples revealed that patient immune parameters are markedly stratified by levels of lymphatic markers. This work suggests that the establishment of tumor-associated inflammation and immunity critically depends on lymphatic vessel remodeling and drainage. Moreover, these results have implications for immunotherapies, the efficacies of which are regulated by the tumor immune microenvironment. PMID:27525437

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

    Science.gov (United States)

    Heppell, Charles; Roose, Tiina; Richardson, Giles

    2015-06-01

    This study investigates fluid flow and elastic deformation in tissues that are drained by the primary lymphatic system. A model is formulated based on the Rossi hypothesis that states that the primary lymphatic valves, which are formed by overlapping endothelial cells around the circumferential lining of lymphatic capillaries, open in response to swelling of the surrounding tissue. Tissue deformation and interstitial fluid flow through the tissue are treated using the Biot equations of poroelasticity and, the fluid flux (into the interstitium) across the walls of the blood capillaries, is assumed to be linearly related to the pressure difference across the walls via a constant of proportionality (the vascular permeability). The resulting model is solved in a periodic domain containing one blood capillary and one lymphatic capillary starting from a configuration in which the tissue is undeformed. On imposition of a constant pressure difference between blood and lymphatic capillaries, the solutions are found to settle to a steady state. Given that the magnitude of pressure fluctuations in the lymphatic system is much smaller than this pressure difference between blood and lymph, it is postulated that the resulting steady-state solution gives a good representation of the state of the tissue under physiological conditions. The effects of changes to the Young's modulus of the tissue, the blood-lymphatic pressure difference, vascular permeability and valve dimensions on the steady state are investigated and discussed in terms of their effects on oedema in the context of age- and pregnancy-related changes to the body. PMID:25911590

  19. Lymphatic vessel development: fluid flow and valve-forming cells.

    Science.gov (United States)

    Kume, Tsutomu

    2015-08-01

    Hemodynamic forces regulate many aspects of blood vessel disease and development, including susceptibility to atherosclerosis and remodeling of primary blood vessels into a mature vascular network. Vessels of the lymphatic circulatory system are also subjected to fluid flow-associated forces, but the molecular and cellular mechanisms by which these forces regulate the formation and maintenance of lymphatic vessels remain largely uncharacterized. This issue of the JCI includes two articles that begin to address how fluid flow influences lymphatic vessel development and function. Sweet et al. demonstrate that lymph flow is essential for the remodeling of primary lymphatic vessels, for ensuring the proper distribution of smooth muscle cells (SMCs), and for the development and maturation of lymphatic valves. Kazenwadel et al. show that flow-induced lymphatic valve development is initiated by the upregulation of GATA2, which has been linked to lymphedema in patients with Emberger syndrome. Together, these observations and future studies inspired by these results have potential to lead to the development of strategies for the treatment of lymphatic disorders. PMID:26214518

  20. The human renal lymphatics under normal and pathological conditions

    OpenAIRE

    Ishikawa, Y.; Akasaka, Y.; Kiguchi, H; Akishima-Fukasawa, Y; Hasegawa, T.; Ito, K.; Kimura-Matsumoto, M; Ishiguro, S.; Morita, H; Sato, S.; Soh, S; Ishii, T.

    2005-01-01

    Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S, Soh S & Ishii T (2006) Histopathology 49, 265–273 The human renal lymphatics under normal and pathological conditions Aims The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. Methods...

  1. Distribution of prosaposin in rat lymphatic tissues.

    Science.gov (United States)

    Shimokawa, Tetsuya; Nabeka, Hiroaki; Yamamiya, Kimiko; Wakisaka, Hiroyuki; Takeuchi, Takashi; Kobayashi, Naoto; Matsuda, Seiji

    2013-06-01

    Prosaposin (PSAP) is as a trophic factor and an activator protein for sphingolipid hydrolase in lysosomes. We generated a specific antibody to PSAP and examined the spatiotemporal distribution of PSAP-immunoreactive (PSAP-IR) cells in the lymphatic tissues of Wistar rats. Immunoblots of tissue homogenates separated electrophoretically showed a single band for PSAP in brain but two bands in spleen. PSAP-IR cells were distributed in both the red and white pulp of the spleen, in both the cortex and medulla of the thymus and in mesenteric lymph nodes. Many PSAP-IR cells were found in the dome portion of Peyer's patches and the number of PSAP-IR cells increased with the age of the rat. To identify the PSAP-IR cells, double- and triple-immunostainings were performed with antibodies against PSAP, CD68 and CD1d. The large number of double- and triple-positive cells suggested that antigen-presenting cells contained much PSAP in these lymphatic tissues. Intense expression of PSAP mRNA, examined by in situ hybridisation, was observed in the red pulp and corona of the spleen. In rats, the PSAP gene generates two alternative splicing forms of mRNA: Pro+9 containing a 9-base insertion and Pro+0 without the insertion. We examined the expression patterns of the alternative splicing forms of PSAP mRNA in the spleen. The presence of both types of mRNA (Pro+9 and Pro+0) indicated that the spleen contains various types of prosaposin-producing and/or secreting cells. These findings suggest diverse functions for PSAP in the immune system. PMID:23420452

  2. The reaction of lymphatic component of hemopoiesis to fractionated irradiation and repeated bone marrow transplantation

    International Nuclear Information System (INIS)

    Mice were repeatedly subjected to individual doses of 60Co-gamma rays at intervals of four days up to total doses of 3, 6, 9, 12, 15, 18, 21 and 24 Gy. Under these conditions, signs of partial adaptation of the lymphatic component of hemopoiesis to conditions of repeated irradiations were found in mice which were given transplants of 106 nuclear cells of syngenetic bone marrow after each irradiation. Systematic findings of statistically significant differences in the values of the lymphatic hemopoietic component parameters studied between bone marrow recipients and animals subjected only to repeated irradiations were recorded after 24th day of experiment in mice which received total doses of 21 and 24 Gy. A positive influence of repeated transplantations in bone marrow recipients became manifested in these experimental groups already upon withdrawals made on day 4 after the last irradiation. A quite pronounced increase in the values of the bone marrow recipients' lymphatic hemopoietic component studied was then recorded upon withdrawals made on day 9 after the last irradiation. (orig.)

  3. Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Bruno Lorusso

    2015-01-01

    Full Text Available 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.

  4. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

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

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

    Science.gov (United States)

    2013-01-01

    Abstract Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce lymphatic dilatation. Progressive lymphatic damage and pathology results primarily from the host inflammatory response to the parasites but also perhaps from the host inflammatory response to the parasite's Wolbachia endosymbiont and as a consequence of superimposed bacterial or fungal infections. This review will attempt to shed light on disease pathogenesis in lymphatic filariasis. PMID:24044755

  6. Adiponectin‐Mediated Modulation of Lymphatic Vessel Formation and Lymphedema

    OpenAIRE

    Shimizu, Yuuki; Shibata, Rei; Ishii, Masakazu; Ohashi, Koji; Kambara, Takahiro; Uemura, Yusuke; Yuasa, Daisuke; Kataoka, Yoshiyuki; Kihara, Shinji; Murohara, Toyoaki; Ouchi, Noriyuki

    2013-01-01

    Background Obesity is linked with an increased risk of lymphedema, which is a serious clinical problem. Adiponectin is a circulating adipokine that is down‐regulated in obese states. We investigated the effects of adiponectin on lymphatic vessel formation in a model of lymphedema and dissected its mechanisms. Methods and Results A mouse model of lymphedema was created via ablation of tail surface lymphatic network. Adiponectin‐knockout mice showed the greater diameter of the injured tail comp...

  7. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2014-01-01

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

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

    OpenAIRE

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

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic ves...

  9. Transmission Dynamics of Lymphatic Filariasis: A Mathematical Approach

    OpenAIRE

    C.P. Bhunu; Mushayabasa, S.

    2012-01-01

    An epidemiological model for the spread of lymphatic filariasis, a mosquito-borne infection, is developed and analysed. The epidemic thresholds known as the reproduction number and equilibria for the model are determined and stabilities analysed. Results from the analysis of the reproduction number suggest that treatment will somehow contribute to a reduction in lymphatic filariasis cases, but what it does not show is the magnitude of the reduction, a part answered by the numerical simulation...

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

  13. 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.

  14. Photoacoustic lymphatic imaging with high spatial-temporal resolution

    Science.gov (United States)

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

    2014-11-01

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

  15. Mechanisms of VIP-induced inhibition of the lymphatic vessel pump.

    Science.gov (United States)

    von der Weid, Pierre-Yves; Rehal, Sonia; Dyrda, Peter; Lee, Stewart; Mathias, Ryan; Rahman, Mozibur; Roizes, Simon; Imtiaz, Mohammad S

    2012-06-01

    Lymphatic vessels serve as a route by which interstitial fluid, protein and other macromolecules are returned to the blood circulation and immune cells and antigens gain access to lymph nodes. Lymph flow is an active process promoted by rhythmical contraction-relaxation events occurring in the collecting lymphatic vessels. This lymphatic pumping is an intrinsic property of the lymphatic muscles in the vessel wall and consequent to action potentials. Compromised lymphatic pumping may affect lymph and immune cell transport, an action which could be particularly detrimental during inflammation. Importantly, many inflammatory mediators alter lymphatic pumping. Vasoactive intestinal peptide (VIP) is a neuro- and immuno-modulator thought to be released by nerve terminals and immune cells in close proximity to lymphatic vessels. We demonstrated the presence of the peptide in lymphatic vessels and in the lymph and examined the effects of VIP on mesenteric collecting lymphatic vessels of the guinea pig using pharmacological bioassays, intracellular microelectrode electrophysiology, immunofluorescence and quantitative real-time PCR. We showed that VIP alters lymphatic pumping by decreasing the frequency of lymphatic contractions and hyperpolarizing the lymphatic muscle membrane potential in a concentration-dependent manner. Our data further suggest that these effects are mainly mediated by stimulation of the VIP receptor VPAC2 located on the lymphatic muscle and the downstream involvement of protein kinase A (PKA) and ATP-sensitive K⁺ (KATP) channels. Inhibition of lymphatic pumping by VIP may compromise lymph drainage, oedema resolution and immune cell trafficking to the draining lymph nodes. PMID:22451438

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-25

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

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

    International Nuclear Information System (INIS)

    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

  18. Light microscopy of the lymphatics of the human atrial wall and lymphatic drainage of supraventricular pacemakers.

    Science.gov (United States)

    Elisková, M; Eliska, O

    1989-01-01

    After injection of Indian ink stained 2% gelatine in 42 human hearts the lymph drainage of the regions of supraventricular cardiac pacemakers and the patterns of the lymphatic vascular bed in the atrial wall were studied. From the sites of the pacemakers the lymph is drained into the tracheobronchial nodes in 100%. Only two of those regions are drained through additional pathways, namely the SAN region into the anterior mediastinal node situated at the azygos vein and the coronary sinus area into the anterior mediastinal lateropericardiac nodes. In the cleared specimens as microscopically the epicardial lymph vessels produce polygonal superficial network; oblique anastomoses of that network run into the deeper layers of subepicardial tissue where they join with deep irregular lymphatic network. Deep subepicardial lymph vessels are often accompanied by veins and nerves. The course of most of myocardial lymph vessels follows the position of muscle cells. In the connective septa these vessels join to form larger trunks and open into the subepicardial vessels. PMID:2475557

  19. 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.

  20. FOXC2 and FLT4 Gene Variants in Lymphatic Filariasis.

    Science.gov (United States)

    Sheik, Yasmeen; Qureshi, Sameera Fatima; Mohhammed, Basheeruddin; Nallari, Pratibha

    2015-06-01

    Lymphatic filariasis is the leading cause of secondary lymphedema wherein lymph transport is impaired due to lymphatic damage. FLT4 signaling and transcription factors such as FOXC2 play an important role in this type of lymphangiogenesis process induced by filarial parasites. The present study aims to assess the association of FLT4 and FOXC2 genes in lymphatic development/remodeling in lymphatic filariasis. A total of 118 lymphatic filariasis patients and 100 non-endemic and 50 endemic healthy subjects were enrolled for the present study. Allele-specific PCR and PCR-RFLP were adopted for the genotyping, and screening of FLT4 and FOXC2 genes was carried out by PCR-SSCP, followed by in-silico and statistical analysis. A novel variation (G357A SNP) was identified on FOXC2 gene screening that may have an effect on codon usage frequency during translational process. In FLT4, A3123G mutation was found in 3.39% of the case subjects but the functional role of this mutation, along with subject's clinical presentations and patient's age, emphasize its pathogenic role in lymphedema development. Two of the subjects exhibit compound heterozygosity (A3123G FLT4 mutation and G357A SNP of FOXC2 gene). As these two genes share a common pathway, we hypothesise a synergistic interaction of these two SNPs in inhibiting the downstream signaling resulting in lymphedema progression.

  1. FOXC2 and FLT4 Gene Variants in Lymphatic Filariasis.

    Science.gov (United States)

    Sheik, Yasmeen; Qureshi, Sameera Fatima; Mohhammed, Basheeruddin; Nallari, Pratibha

    2015-06-01

    Lymphatic filariasis is the leading cause of secondary lymphedema wherein lymph transport is impaired due to lymphatic damage. FLT4 signaling and transcription factors such as FOXC2 play an important role in this type of lymphangiogenesis process induced by filarial parasites. The present study aims to assess the association of FLT4 and FOXC2 genes in lymphatic development/remodeling in lymphatic filariasis. A total of 118 lymphatic filariasis patients and 100 non-endemic and 50 endemic healthy subjects were enrolled for the present study. Allele-specific PCR and PCR-RFLP were adopted for the genotyping, and screening of FLT4 and FOXC2 genes was carried out by PCR-SSCP, followed by in-silico and statistical analysis. A novel variation (G357A SNP) was identified on FOXC2 gene screening that may have an effect on codon usage frequency during translational process. In FLT4, A3123G mutation was found in 3.39% of the case subjects but the functional role of this mutation, along with subject's clinical presentations and patient's age, emphasize its pathogenic role in lymphedema development. Two of the subjects exhibit compound heterozygosity (A3123G FLT4 mutation and G357A SNP of FOXC2 gene). As these two genes share a common pathway, we hypothesise a synergistic interaction of these two SNPs in inhibiting the downstream signaling resulting in lymphedema progression. PMID:26091406

  2. Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy.

    Science.gov (United States)

    Abellan-Pose, Raquel; Csaba, Noemi; Alonso, Maria Jose

    2016-01-01

    The lymphatic system represents a major route of dissemination in metastatic cancer. Given the lack of selectivity of conventional chemotherapy to prevent lymphatic metastasis, in the last years there has been a growing interest in the development of nanocarriers showing lymphotropic characteristics. The goal of this lymphotargeting strategy is to facilitate the delivery of anticancer drugs to the lymph node-resident cancer cells, thereby enhancing the effectiveness of the anti-cancer therapies. This article focuses on the nanosystems described so far for the active or passive targeting of oncological drugs to the lymphatic circulation. To understand the design and performance of these nanosystems, we will discuss first the physiology of the lymphatic system and how physiopathological changes associated to tumor growth influence the biodistribution of nanocarriers. Second, we provide evidence on how the tailoring of the physicochemical characteristics of nanosystems, i.e. particle size, surface charge and hydrophilicity, allows the modulation of their access to the lymphatic circulation. Finally, we provide an overview of the relationship between the biodistribution and antimetastatic activity of the nanocarriers loaded with oncological drugs, and illustrate the most promising active targeting approaches investigated so far. PMID:26675222

  3. Elimination of lymphatic filariasis in the Gambia.

    Directory of Open Access Journals (Sweden)

    Maria P Rebollo

    2015-03-01

    Full Text Available The prevalence of Wuchereria bancrofti, which causes lymphatic filariasis (LF in The Gambia was among the highest in Africa in the 1950s. However, surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration (MDA. The decline in prevalence was partly attributed to a significant reduction in mosquito density through the widespread use of insecticidal nets. Based on findings elsewhere that vector control alone can interrupt LF, we asked the question in 2013 whether the rapid scale up in the use of insecticidal nets in The Gambia had interrupted LF transmission.We present here the results of three independently designed filariasis surveys conducted over a period of 17 years (1997-2013, and involving over 6000 subjects in 21 districts across all administrative divisions in The Gambia. An immunochromatographic (ICT test was used to detect W. bancrofti antigen during all three surveys. In 2001, tests performed on stored samples collected between 1997 and 2000, in three divisions, failed to show positive individuals from two divisions that were previously highly endemic for LF, suggesting a decline towards extinction in some areas. Results of the second survey conducted in 2003 showed that LF was no longer endemic in 16 of 21 districts surveyed. The 2013 survey used a WHO recommended LF transmission verification tool involving 3180 6-7 year-olds attending 60 schools across the country. We demonstrated that transmission of W. bancrofti has been interrupted in all 21 districts.We conclude that LF transmission may have been interrupted in The Gambia through the extensive use of insecticidal nets for malaria control for decades. The growing evidence for the impact of malaria vector control activities on parasite transmission has been endorsed by WHO through a position statement in 2011 on integrated vector management to control malaria and LF.

  4. Anatomy and development of the cardiac lymphatic vasculature: Its role in injury and disease.

    Science.gov (United States)

    Norman, Sophie; Riley, Paul R

    2016-04-01

    Lymphatic vessels are present throughout the entire body in all mammals and function to regulate tissue fluid balance, lipid transport and survey the immune system. Despite the presence of an extensive lymphatic plexus within the heart, until recently the importance of the cardiac lymphatic vasculature and its origins were unknown. Several studies have described the basic anatomy of the developing cardiac lymphatic vasculature and more recently the detailed development of the murine cardiac lymphatics has been documented, with important insight into their cellular sources during embryogenesis. In this review we initially describe the development of systemic lymphatic vasculature, to provide the background for a comparative description of the spatiotemporal development of the cardiac lymphatic vessels, including detail of both canonical, typically venous, and noncanonical (hemogenic endothelium) cellular sources. Subsequently, we address the response of the cardiac lymphatic network to myocardial infarction (heart attack) and the therapeutic potential of targeting cardiac lymphangiogenesis. PMID:26443964

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

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Zhang; Wei-Yue Lu

    2014-01-01

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

  6. From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity.

    Science.gov (United States)

    Trevaskis, Natalie L; Kaminskas, Lisa M; Porter, Christopher J H

    2015-11-01

    The lymphatic system serves an integral role in fluid homeostasis, lipid metabolism and immune control. In cancer, the lymph nodes that drain solid tumours are a primary site of metastasis, and recent studies have suggested intrinsic links between lymphatic function, lipid deposition, obesity and atherosclerosis. Advances in the current understanding of the role of the lymphatics in pathological change and immunity have driven the recognition that lymph-targeted delivery has the potential to transform disease treatment and vaccination. In addition, the design of lymphatic delivery systems has progressed from simple systems that rely on passive lymphatic access to sophisticated structures that use nanotechnology to mimic endogenous macromolecules and lipid conjugates that 'hitchhike' onto lipid transport processes. Here, we briefly summarize the lymphatic system in health and disease and the varying mechanisms of lymphatic entry and transport, as well as discussing examples of lymphatic delivery that have enhanced therapeutic utility. We also outline future challenges to effective lymph-directed therapy. PMID:26471369

  7. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses.

    Directory of Open Access Journals (Sweden)

    Kimberly L Jordan-Williams

    Full Text Available Lymphocyte- and leukocyte-mediated lymph node (LN lymphatic sinus growth (lymphangiogenesis is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses.

  8. The Lymphatic Endothelial mCLCA1 Antibody Induces Proliferation and Growth of Lymph Node Lymphatic Sinuses.

    Science.gov (United States)

    Jordan-Williams, Kimberly L; Ramanujam, Neela; Farr, Andrew G; Ruddell, Alanna

    2016-01-01

    Lymphocyte- and leukocyte-mediated lymph node (LN) lymphatic sinus growth (lymphangiogenesis) is involved in immune responses and in diseases including cancer and arthritis. We previously discovered a 10.1.1 Ab that recognizes the lymphatic endothelial cell (LEC) surface protein mCLCA1, which is an interacting partner for LFA1 and Mac-1 that mediates lymphocyte adhesion to LECs. Here, we show that 10.1.1 Ab treatment specifically induces LEC proliferation, and influences migration and adhesion in vitro. Functional testing by injection of mice with 10.1.1 Ab but not control hamster Abs identified rapid induction of LN LEC proliferation and extensive lymphangiogenesis within 23 h. BrdU pulse-chase analysis demonstrated incorporation of proliferating LYVE-1-positive LEC into the growing medullary lymphatic sinuses. The 10.1.1 Ab-induced LN remodeling involved coordinate increases in LECs and also blood endothelial cells, fibroblastic reticular cells, and double negative stroma, as is observed during the LN response to inflammation. 10.1.1 Ab-induced lymphangiogenesis was restricted to LNs, as mCLCA1-expressing lymphatic vessels of the jejunum and dermis were unaffected by 23 h 10.1.1 Ab treatment. These findings demonstrate that 10.1.1 Ab rapidly and specifically induces proliferation and growth of LN lymphatic sinuses and stroma, suggesting a key role of mCLCA1 in coordinating LN remodeling during immune responses. PMID:27224029

  9. Lymphatic drainage from the eye: A new target for therapy.

    Science.gov (United States)

    Yucel, Yeni; Gupta, Neeru

    2015-01-01

    Lowering intraocular pressure (IOP) has been central to glaucoma care for over a century. In order to prevent sight loss from disease, there has been considerable focus on medical and surgical methods to improve fluid drainage from the eye. In spite of this, our understanding of exactly how aqueous humor leaves the eye is not complete. Recently, lymphatic vessels have been discovered in the human uvea, with studies showing lymphatic fluid outflow in several models, in addition to evidence for their pharmacological enhancement. The presence of a lymphatic outflow system points to an exciting, expanded understanding of how fluid and particulate materials such as proteins move out of the eye, and how IOP may be regulated. We coin the term "uveolymphatic pathway"-to reflect a comprehensive and compelling new target for glaucoma and an exciting opportunity for future investigations to better understand the eye in health and disease. PMID:26497791

  10. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

    DEFF Research Database (Denmark)

    Koltowska, Katarzyna; Lagendijk, Anne Karine; Pichol-Thievend, Cathy;

    2015-01-01

    Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics...... during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter...

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

    Science.gov (United States)

    Ji, R C; Kato, S

    1997-07-01

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

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

    Science.gov (United States)

    Ji, R C; Kato, S

    1997-07-01

    Postnatal development of rat gastric lymphatics was studied by an enzyme-histochemical method to elucidate the morphological changes of lymphatics and their relationship to maturation and function, especially in the glandular portion. The significant features of 5'-Nase-positive lymphatics in distribution and structure were examined in different stages (within 24 hr, 4-21 days, and 2 months). Lymphatics in the greater curvature and anterior wall grew much slower than those in the lesser curvature and posterior wall of the stomach in newborn and infant rats. Lymphatic islands isolated from the primary lymphatic networks in the submucosa and subserosa underwent a morphological change during this early period. This is considered one of the basic steps in lymphatic development. Occurrence of lymphatic networks in the deep lamina propria indicates that development in the gastric wall is well characterized from Day 10. With further growth and modification of lymphatics, the networks in the different layers formed an extensive communication network and many lymphatic valves were found in the submucosa and subserosa. Pinocytotic vesicles, open junctions, and intraendothelial channels were frequently detected in the mucosal and submucosal lymphatic networks of the corpus-antrum and antrum-duodenum divisional zones in the adult rats. These findings suggest that developing lymphatics in the rat stomach may represent rapidly growing tissue not only with high 5'-Nase activity but also with high adaptability for future physiological demands. PMID:9245639

  13. Lymphatic disorders after renal transplantation: new insights for an old complication.

    Science.gov (United States)

    Ranghino, Andrea; Segoloni, Giuseppe Paolo; Lasaponara, Fedele; Biancone, Luigi

    2015-10-01

    In renal transplanted patients, lymphoceles and lymphorrhea are well-known lymphatic complications. Surgical damage of the lymphatics of the graft during the procurement and of the lymphatic around the iliac vessels of the recipients has been associated with development of lymphatic complications. However, lymphatic complications may be related to medical factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs. Consistently, immunosuppression regimens based on the use of mTOR inhibitors, especially in association with steroids and immediately after transplantation, has been associated with a high risk to develop lymphocele or lymphorrhea. In addition, several studies have demonstrated the association between rejection episodes and lymphatic complications. However, before the discovery of reliable markers of lymphatic vessels, the pathogenic mechanisms underlining the development of lymphatic complications during rejection and the influence of mTOR inhibitors remained not fully understood. The recent findings on the lymphatic systems of either native or transplanted kidneys together with the advances achieved on lymphangiogenesis shared some lights on the pathogenesis of lymphatic complications after renal transplantation. In this review, we describe the surgical and medical causes of lymphatic complications focusing on the rejection and immunosuppressive drugs as causes of lymphatic complications. PMID:26413290

  14. 白花蛇舌草抑制肝癌H22小鼠淋巴管转移的实验研究%Experimental Study on Inhibitory Effect of Hedyotis Diffusa Willd on Lymphatic Metastasis of Mice with Hepatocarcinoma H22

    Institute of Scientific and Technical Information of China (English)

    李洁; 李怀芝; 韩冰冰

    2014-01-01

    目的:观察白花蛇舌草对小鼠肝癌淋巴管转移的影响。方法:在小鼠右下肢爪垫内侧皮下注射接种腹水型肝癌H22瘤株,复制淋巴管转移模型。将模型小鼠随机分为5组,空白组每天灌生理盐水,大、中、小剂量组每天灌白花蛇舌草水煎液,对照组给予环磷酰胺腹腔注射。观察小鼠体质量、免疫器官、肺部转移率、爪垫移植瘤、淋巴结转移瘤等指标变化。结果:白花蛇舌草作用组的小鼠,体质量和免疫器官胸腺质量明显增长,肺部瘤结节数和肺部转移瘤生长指数均下降,且淋巴结转移数明显减少。结论:白花蛇舌草对H22肝癌淋巴管转移有一定抑制作用。%Objective:To observe effects of Hedyotis diffusa Willd in treating hepatocarcinoma lymphatic metastasis of mice. Methods:The H22 lymphatic metastasis models were established by subcutaneous injecting H22 cell line into the palmula of right lower limb. The model mice were randomly divided into 5 groups. The blank group was given normal saline daily,and large,medium,small-dose group were given Hedyotis diffusa Willd,and the control group were received cyclophosphamide by intraperitoneal injection daily. The changes of mouse’s body weight,the weight of immune organ,lung metastasis,paw pads transplantation tumor and lymph node metastasis were observed. Results:In Hedyotis diffusa Willd group,body weight and the weight of immune organs increased,lung nodules and lung metastasis tumor growth index were decreased,and the number of lymph node metastases was reduced. Conclusion:Hedyotis diffusa Willd has an inhibitory ef-fect on the metastasis of hepatocarcinoma lymphatic.

  15. The meningeal lymphatic system: a route for HIV brain migration?

    Science.gov (United States)

    Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S

    2016-06-01

    Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system. PMID:26572785

  16. Pkd1 regulates lymphatic vascular morphogenesis during development

    NARCIS (Netherlands)

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

    2014-01-01

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

  17. Malaria and lymphatic filariasis: the case for integrated vector management

    NARCIS (Netherlands)

    Berg, van den H.; Kelly-Hope, L.A.; Lindsay, S.W.

    2013-01-01

    The global programmes to eliminate both malaria and lymphatic filariasis are facing operational and technical challenges. Available data show that the use of treated or untreated bednets and indoor residual spraying for malaria control concomitantly reduced filarial rates. In turn, mass drug adminis

  18. The Socioeconomic Impact of Lymphatic Filariasis in Tropical Countries

    Science.gov (United States)

    Nwoke, Bertram Ekejiuba Bright; Nwoke, Eunice Anyalewechi; Dozie, Ikechukwu Nosike Simplicius

    2007-01-01

    Lymphatic filariasis (LF) is an endemic parasitic disease and a major cause of acute and chronic morbidity and incapacitation with devastating public health and socio-economic consequences. It exacerbates poor conditions of afflicted persons and endemic communities through reduced or lost labour supply and productivity. Stigmatisation and…

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  20. Lymphatic filariasis: diagnosis and pathogenesis. WHO expert committee on filariasis.

    OpenAIRE

    1993-01-01

    In the past few years, knowledge of many aspects of lymphatic filariasis, s debilitating disease with serious economic and social consequences, has increased. This article presents sections on diagnosis, pathogenesis, immunopathology and protective immunity from the recently published Expert Committee's report.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-15

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

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

    Directory of Open Access Journals (Sweden)

    Lukas Stanczuk

    2015-03-01

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

  5. A computational and functional study elicits the ameliorating effect of the Chinese herbal formula Huo Luo Xiao Ling Dan on experimental ischemia-induced myocardial injury in rats via inhibition of apoptosis.

    Science.gov (United States)

    Han, Xiang-Dong; Zhou, Zhi-Wei; Yang, Wei; Ye, Hang-Cheng; Xu, Ying-Zi; Huang, Yun-Feng; Zhang, Tong; Zhou, Shu-Feng

    2015-01-01

    of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD.

  6. LyP-1-conjugated doxorubicin-loaded liposomes suppress lymphatic metastasis by inhibiting lymph node metastases and destroying tumor lymphatics

    Energy Technology Data Exchange (ETDEWEB)

    Yan Zhiqiang; Zhan Changyou; Wen Ziyi; Feng Linglin; Wang Fei; Liu Yu; Yang Xiangkun; Dong Qing; Liu Min; Lu Weiyue, E-mail: wylu@shmu.edu.cn [Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203 (China)

    2011-10-14

    Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

  7. Lymphatic filariasis in India: Epidemiology and control measures

    Directory of Open Access Journals (Sweden)

    Sabesan S

    2010-01-01

    Full Text Available Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is an important public health problem in India. Both parasites produce essentially similar clinical presentations in man, related mainly to the pathology of the lymphatic system. Filariasis is endemic in 17 States and six Union Territories, with about 553 million people at risk of infection. The Government of India has accorded a high priority for elimination of this infection through mass chemotherapy programme (annual, single dose of Diethylcarbamazine citrate, i.e. DEC - 6 mg/kg of bodyweight, plus Albendazole repeated four to six times. This campaign has become a part of the National Vector-Borne Disease Control Programme in 2003 under the National Health Policy 2002 and aims to eliminate filariasis by 2015. We discuss here the epidemiology and current control strategy for filariasis; highlighting key issues, challenges and options in the implementation of the programme, and suggesting measures for mid-course corrections in the elimination strategy.

  8. Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration

    Science.gov (United States)

    Brinkman, C. Colin; Iwami, Daiki; Hritzo, Molly K.; Xiong, Yanbao; Ahmad, Sarwat; Simon, Thomas; Hippen, Keli L.; Blazar, Bruce R.; Bromberg, Jonathan S.

    2016-01-01

    Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression. PMID:27323847

  9. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, N; Simonsen, L; Holst, Jens Juul;

    2012-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after...... an oral glucose load. Adipose-tissue blood flow was measured in the anterior subcutaneous abdominal adipose tissue by the (133)Xe-washout technique. ATLD was measured as the disappearance rate of (99m)Tc-labelled nanoaggregated human albumin, during fasting and after an oral glucose load. A significant...... the lymphatic system in obese subjects. Furthermore, they suggest that postprandial changes in ATLD taking place in lean subjects are not observed in obese subjects. This may have a role in the development of obesity-related inflammation in hypertrophic adipose tissue.International Journal of Obesity advance...

  10. Setaria digitata in advancing our knowledge of human lymphatic filariasis.

    Science.gov (United States)

    Perumal, A N I; Gunawardene, Y I N S; Dassanayake, R S

    2016-03-01

    Setaria digitata is a filarial parasite that causes fatal cerebrospinal nematodiasis in goats, sheep and horses, resulting in substantial economic losses in animal husbandry in the tropics. Due to its close resemblance to Wuchereria bancrofti, this nematode is also frequently used as a model organism to study human lymphatic filariasis. This review highlights numerous insights into the morphological, histological, biochemical, immunological and genetic aspects of S. digitata that have broadened our understanding towards the control and eradication of filarial diseases. PMID:25924635

  11. Imported lymphatic filariasis in an Indian immigrant to iran.

    Directory of Open Access Journals (Sweden)

    Eshrat Beigom Kia

    2014-03-01

    Full Text Available Lymphatic filariasis (LF, a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical characteristics of microfilaria and PCR sequencing.

  12. Imported lymphatic filariasis in an Indian immigrant to iran.

    Science.gov (United States)

    Kia, Eshrat Beigom; Sharifdini, Meysam; Hajjaran, Homa; Shahbazi, Ali Ehsan; Sayyad Talaie, Zahra

    2014-03-01

    Lymphatic filariasis (LF), a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical characteristics of microfilaria and PCR sequencing. PMID:25642273

  13. Host protective immunity and vaccine development studies in lymphatic filariasis

    OpenAIRE

    Reddy, M. V. R.; Alli, R.; Harinath, B. C.

    2000-01-01

    Lymphatic filariasis caused mainly by infection fromWuchereria bancrofti andBrugia malayi remains as the major cause of clinical morbidity in tropical and subtropical countries. Development of vaccine against filarial infection can act as additional measure to the existing therapeutic and vector control methods in the control of this disease. The main hurdles in the development of anti-filarial vaccine are the strict primate specificity ofWuchereria bancrofti, the paucity of parasite material...

  14. Follicular thyroid carcinoma invades venous rather than lymphatic vessels

    Directory of Open Access Journals (Sweden)

    Liu Yulin

    2010-01-01

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

  15. National Mass Drug Administration Costs for Lymphatic Filariasis Elimination

    OpenAIRE

    Goldman, Ann S; Victoria H Guisinger; Moses Aikins; Maria Lourdes E Amarillo; Belizario, Vicente Y.; Bertha Garshong; John Gyapong; Conrad Kabali; Kamal, Hussein A.; Sanjat Kanjilal; Dominique Kyelem; Jefrey Lizardo; Mwele Malecela; Godfrey Mubyazi; P Abdoulaye Nitièma

    2007-01-01

    BACKGROUND: Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to ...

  16. Baseline drivers of lymphatic filariasis in Burkina Faso

    OpenAIRE

    Stanton, Michelle C.; Molyneux, David H; Dominique Kyelem; Bougma, Roland W; Koudou, Benjamin G; Louise A Kelly-Hope

    2013-01-01

    Lymphatic filariasis (LF) is a parasitic disease that is endemic throughout sub-Saharan Africa, infecting approximately 40 million people. In Burkina Faso, mass drug administration (MDA) for LF with ivermectin and albendazole has been ongoing since 2001, and by 2006 all endemic health districts were receiving MDA with a therapeutic coverage of at least 65%. As MDA activities scale down, the focus is now on targeting areas where LF transmission persists with alternative elimination strategies....

  17. Incidentally Detected Lymphatic Filariasis in a Renal Allograft Recipient

    OpenAIRE

    Vanikar, A. V.; Suthar, K. S.; Kute, V. B.; Rizvi, S. J.; Trivedi, H. L.

    2013-01-01

    Post-transplntation lymphocele is a well known complication, and lymphatic filariasis (LF) has occasionally been found to present as post-transplantation lymphocele. However, incidentally detected LF during transplantation surgery has not been reported. We present an incidentally detected LF presenting as enlarged lymph node in the right iliac fossa of a recipient during transplantation of donor kidney. He was subsequently treated after transplantation and had stable graft function without an...

  18. Incidentally Detected Lymphatic Filariasis in a Renal Allograft Recipient

    Science.gov (United States)

    Vanikar, A. V.; Suthar, K. S.; Kute, V. B.; Rizvi, S. J.; Trivedi, H. L.

    2013-01-01

    Post-transplntation lymphocele is a well known complication, and lymphatic filariasis (LF) has occasionally been found to present as post-transplantation lymphocele. However, incidentally detected LF during transplantation surgery has not been reported. We present an incidentally detected LF presenting as enlarged lymph node in the right iliac fossa of a recipient during transplantation of donor kidney. He was subsequently treated after transplantation and had stable graft function without any complications after 8 months of follow-up. PMID:25013664

  19. Mapping the geographical distribution of lymphatic filariasis in Zambia

    OpenAIRE

    Mwase, Enala T; Anna-Sofie Stensgaard; Mutale Nsakashalo-Senkwe; Likezo Mubila; James Mwansa; Peter Songolo; Sheila T Shawa; Paul E Simonsen

    2014-01-01

    BACKGROUND: Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control, a country-wide mapping survey was undertaken between 2003 and 2011. Here the mapping activities are outlined, the findings across the numerous survey sites are presented, and the ecological requireme...

  20. The burden of mental health in lymphatic filariasis

    OpenAIRE

    Ton, Thanh G. N.; Mackenzie, Charles; Molyneux, David H

    2015-01-01

    Background Neglected Tropical Diseases (NTDs) afflict around one billion individuals in the poorest parts of the world with many more at risk. Lymphatic filariasis is one of the most prevalent of the infections and causes significant morbidity in those who suffer the clinical conditions, particularly lymphedema and hydrocele. Depressive illness has been recognised as a prevalent disability in those with the disease because of the stigmatising nature of the condition. No estimates of the burde...

  1. Modelling Co-Infection with Malaria and Lymphatic Filariasis

    OpenAIRE

    Slater, Hannah C.; Manoj Gambhir; Parham, Paul E; Edwin Michael

    2013-01-01

    Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies ...

  2. Drug targets for lymphatic filariasis: A bioinformatics approach

    OpenAIRE

    Om Prakash Sharma; Yellamandaya Vadlamudi; Arun Gupta Kota; Vikrant Kumar Sinha; Muthuvel Suresh Kumar

    2013-01-01

    This review article discusses the current scenario of the national and international burden due to lymphatic filariasis (LF) and describes the active elimination programmes for LF and their achievements to eradicate this most debilitating disease from the earth. Since, bioinformatics is a rapidly growing field of biological study, and it has an increasingly significant role in various fields of biology. We have reviewed its leading involvement in the filarial research using different approach...

  3. Imported lymphatic filariasis in an Indian immigrant to iran.

    OpenAIRE

    Eshrat Beigom Kia; Meysam Sharifdini; Homa Hajjaran; Ali Ehsan Shahbazi; Zahra Sayyad Talaie

    2014-01-01

    Lymphatic filariasis (LF), a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical c...

  4. Population Migration: Implications for Lymphatic Filariasis Elimination Programmes

    OpenAIRE

    Ramaiah, K. D.

    2013-01-01

    Human population migration is a common phenomenon in developing countries. Four categories of migration-endemic to nonendemic areas, rural to urban areas, non-MDA areas to areas that achieved lymphatic filariasis (LF) control/elimination, and across borders-are relevant to LF elimination efforts. In many situations, migrants from endemic areas may not be able to establish active transmission foci and cause infection in local people in known nonendemic areas or countries. Urban areas are at ri...

  5. The resurgence of lymphatic filariasis in the Nile delta.

    OpenAIRE

    Harb, M.; Faris, R; Gad, A. M.; Hafez, O. N.; Ramzy, R.; Buck, A. A.

    1993-01-01

    A study of 325,000 residents of 314 villages in six governorates of the Nile delta area of Egypt revealed that the prevalence of lymphatic filariasis increased from 20% in 1991, especially in the governorates of Qalyubiya, Monufiya, Dakhaliya, and Giza. The distribution of the communites with endemic filariasis is focal. Clusters of villages with high prevalences are surrounded by others in which the disease is absent, although their environmental, social, and agricultural f...

  6. A computational and functional study elicits the ameliorating effect of the Chinese herbal formula Huo Luo Xiao Ling Dan on experimental ischemia-induced myocardial injury in rats via inhibition of apoptosis

    Directory of Open Access Journals (Sweden)

    Han XD

    2015-02-01

    ADMET (absorption, distribution, metabolism, excretion and toxicity Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD. Keywords: Huo Luo Xiao Ling Dan, myocardial ischemia, coronary artery ligation, hemodynamics, apoptosis, molecular docking

  7. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

    Directory of Open Access Journals (Sweden)

    Ali Khan A

    2013-07-01

    Full Text Available Arshad Ali Khan, Jahanzeb Mudassir, Noratiqah Mohtar, Yusrida Darwis School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia Abstract: The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects

  8. Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

    Science.gov (United States)

    Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

    2016-01-01

    In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

  9. Eicosanoid generation and responsiveness of human lymphatics in hyperlipoproteinemia.

    Science.gov (United States)

    Oguogho, A; Kaliman, J; Sinzinger, H

    2000-01-01

    In this work, the oxidation injury in hyperlipoproteinemia (HLP) was determined by measuring the isoprostane 8-epi-prostaglandin (PG) F2alpha in human lymphatics, lymph fluid, plasma, serum and urine. Lymphatics from 6 patients with HLP generated less PGI2 and contained more 8-epi-PGF2alpha as compared to 6 normolipemics without risk factors. Likewise, plasma (29.3 vs 19.7 pg/ml), lymph fluid (137.3 vs 65.3 pg/ml), serum (286.7 vs 204.1 pg/ml) and urinary (360.8 vs 241.0 pg/mg creatinine) values of 8-epi-PGF2alpha in HLP (as compared to normolipemics) were significantly elevated. Lymphatics from HLP showed an enhanced contractile response, less 14C-arachidonic acid conversion to PGI2 and less PGI2-formation upon various stimuli compared to normolipemics of comparable age. These findings indicate that HLP-induced oxidation injury, resulting in an altered (iso-)eicosanoid production and function, may also significantly affect (patho-) physiology of lymphathics. PMID:10765978

  10. Effect of hepatoma H22 on lymphatic endothelium in vitro

    Institute of Scientific and Technical Information of China (English)

    Hua Yu; Hong-Zhi Zhou; Chun-Mei Wang; Xiao-Ming Gu; Bo-Rong Pan

    2004-01-01

    AIM: To determine the effect of metastatic hepatoma cells on lymphangioma-derived endothelium, and to establish in vitro model systems for assessing metastasis-related response of lymphatic endothelium.METHODS: Benign lymphangioma, induced by intraperitonea linjection of the incomplete Freund's adjuvant in BALB/c mice, was embedded in fibrin gel or digested and then cultured in the conditioned medium derived from hepatoma H22. Light and electron microscopy, and the transwell migration assay were used to determine the effect of H22 on tissue or cell culture. Expressions of Flt-4, c-Fos, proliferating cell nuclear antigen (PCNA), and inducible nitric oxide synthase (iNOS) in cultured cells, and content of nitric oxide in culture medium were also examined.RESULTS: The embedded lymphangioma pieces gave rise to array of capillaries, while separated cells from lymphangioma grew to a cobblestone-like monolayer. H22 activated growth and migration of the capillaries and cells, induced expressions of Flt-4, c-Fos, PCNA and iNOS in cultured cells, and significantly increased the content of NO in the culture medium.CONCLUSION: Lymphangioma-derived cells keep the differentiated phenotypes of lymphatic endothelium, and the models established in this study are feasible for in vitro study of metastasis-related response of lymphatic endothelium.

  11. Lymphatic metastasis and nm23H1 genetic instability in Chinese colon cancer patients

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Su; Ji-Cheng Li

    2004-01-01

    AIM: To investigate the pathogenic mechanism of colon cancer at the molecular level and to elucidate the relationship between intercellular adhesion molecule-1 (ICAM-1) and nm23H1 genes and Chinese patients with colon cancer.METHODS: DNA was extracted from paraffin-embedded materials. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze MSI and LOH. Expression of ICAM-1 was detected by Envision immunohistochemistry. Experimental results were analyzed with Leica-Qwin computer imaging techniques and SPSS software of statistics.RESULTS: ICAM-1 expression of lymphatic endothelium was negative in normal colon and positive in colon cancer respedively.The number of lymphatics positive for ICAM-1 was gradually increased with degree of cancer invasion (P<0.01). In the group with metastasis of colon cancer, the number of lymphatics positive for ICAM-1 in lymph nodes was more than that in the group with no metastasis (P<0.01). The frequency of MSI, LOH and nm23H1 protein was 26.67%, 20.00% and 53.33% in colon cancer, respectively. In TNM staging, MSI (43.75%) and nm23H1 protein (81.25%) in stages Ⅰ+Ⅱ were detected more easily than the corresponding indexes (MSI:7.14%, P<0.05 and nm23H1: 21.43%, P<0.01) in stages Ⅲ+Ⅳ. By comparison, the frequency of LOH (35.71%) in stages Ⅲ+Ⅳ was more than that of LOH (6.25%, P<0.05)in stages Ⅰ+Ⅱ. LOH exhibited a rising trend along with the Duke's staging. nm23H1 protein in the group of tubular adenocarcinoma (60.00%) was higher expressed than that in the group of mucoid adenocarcinoma (20.00%) (P<0.01),and exhibited a rising trend with the differentiation degrees of tubular adenocarcinoma. nm23H1 protein in MSI positive group was higher expressed (75%) than that in MSI negative group (45.45%, P<0.05).CONCLUSION: The expression of ICAM-1 in lymphatic vessels is beneficial to the judgement of the invasion and metastasis ability of colon cancer and the anti-tumor immunity

  12. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish.

    Science.gov (United States)

    Koltowska, Katarzyna; Lagendijk, Anne Karine; Pichol-Thievend, Cathy; Fischer, Johanna C; Francois, Mathias; Ober, Elke A; Yap, Alpha S; Hogan, Benjamin M

    2015-12-01

    Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division. PMID:26655899

  13. Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer's Disease?

    Science.gov (United States)

    Louveau, Antoine; Da Mesquita, Sandro; Kipnis, Jonathan

    2016-09-01

    Lymphatic vasculature drains interstitial fluids, which contain the tissue's waste products, and ensures immune surveillance of the tissues, allowing immune cell recirculation. Until recently, the CNS was considered to be devoid of a conventional lymphatic vasculature. The recent discovery in the meninges of a lymphatic network that drains the CNS calls into question classic models for the drainage of macromolecules and immune cells from the CNS. In the context of neurological disorders, the presence of a lymphatic system draining the CNS potentially offers a new player and a new avenue for therapy. In this review, we will attempt to integrate the known primary functions of the tissue lymphatic vasculature that exists in peripheral organs with the proposed function of meningeal lymphatic vessels in neurological disorders, specifically multiple sclerosis and Alzheimer's disease. We propose that these (and potentially other) neurological afflictions can be viewed as diseases with a neuro-lympho-vascular component and should be therapeutically targeted as such. PMID:27608759

  14. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

    Directory of Open Access Journals (Sweden)

    Katarzyna Koltowska

    2015-12-01

    Full Text Available Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.

  15. Current Status of Lymphatic Reconstructive Surgery for Chronic Lymphedema: It Is Still an Uphill Battle!

    OpenAIRE

    Lee, B.B.; Laredo, J.; Neville, R.

    2011-01-01

    The goal of reconstructive lymphatic surgery is to restore normal lymphatic function to “cure” permanently the lymphedematous limb in patients with lymphedema. In reality, reconstructive surgery remains an adjunctive treatment at best, with its current indication being refractory lymphedema in patients treated with complex decongestive therapy (CDT) alone. The role of reconstructive lymphatic surgery remains controversial and is far from being accepted as standard independent therapy because ...

  16. Are we nearly there yet? Coverage and compliance of mass drug administration for lymphatic filariasis elimination.

    OpenAIRE

    Alexander, ND

    2015-01-01

    : Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drug administration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for ...

  17. Comparison of the Blood and Lymphatic Microvessel Density of Pleomorphic Adenoma and Basal Cell Adenoma

    OpenAIRE

    Andresa Borges Soares; Albina Altemani; Thais Ribeiro de Oliveira; Felipe de Oliveira Fonseca Rodrigues; Alfredo Ribeiro-Silva; Danilo Figueiredo Soave; Fabricio Passador-Santos; Suellen Trentin Brum; Marcelo Henrique Napimoga; Vera Cavalcanti de Araújo

    2015-01-01

    BACKGROUND Pleomorphic adenoma (PA) is the most common tumor of the salivary gland, while basal cell adenoma (BCA) is an uncommon neoplasm. Blood and lymphatic vessels are crucial for tumor metabolism. The aim of this study was to compare the blood and lymphatic vascular density and vascular and endothelial growth factor (VEGF) expression in PA and BCA tumors. In addition, cell proliferation was evaluated in these tumors. METHODS Blood and lymphatic vessel content, VEGF expression, and cell p...

  18. Unfulfilled potential: using diethylcarbamazine-fortified salt to eliminate lymphatic filariasis

    OpenAIRE

    Lammie, Patrick; Milner, Trevor; Houston, Robin

    2007-01-01

    Fortifying salt with diethylcarbamazine (DEC) is a safe, low-cost and effective strategy to eliminate transmission of lymphatic filariasis. DEC-fortified salt has been used successfully in pilot projects in several countries and has been used operationally by China to eliminate lymphatic filariasis. The successful use of iodized salt to eliminate iodine-deficiency disorders is encouraging; similarly, fortified salt could be used as a vehicle to eliminate lymphatic filariasis. Despite the pote...

  19. Direct evidence of lymphatic function improvement after advanced pneumatic compression device treatment of lymphedema

    OpenAIRE

    Adams, Kristen E.; Rasmussen, John C.; Darne, Chinmay; Tan, I-Chih; Aldrich, Melissa B.; Marshall, Milton V.; Fife, Caroline E.; Maus, Erik A.; Smith, Latisha A.; Guilloid, Renie; Hoy, Sunday; Sevick-Muraca, Eva M.

    2010-01-01

    Lymphedema affects up to 50% of all breast cancer survivors. Management with pneumatic compression devices (PCDs) is controversial, owing to the lack of methods to directly assess benefit. This pilot study employed an investigational, near-infrared (NIR) fluorescence imaging technique to evaluate lymphatic response to PCD therapy in normal control and breast cancer-related lymphedema (BCRL) subjects. Lymphatic propulsion rate, apparent lymph velocity, and lymphatic vessel recruitment were mea...

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

    OpenAIRE

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

    2016-01-01

    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 pe...

  1. Exosomes derived from atorvastatin-modified bone marrow dendritic cells ameliorate experimental autoimmune myasthenia gravis by up-regulated levels of IDO/Treg and partly dependent on FasL/Fas pathway

    OpenAIRE

    Li, Xiao-Li; Li, Heng; Zhang, Min; Xu, Hua; Yue, Long-Tao; Zhang, Xin-Xin; Wang, Shan; Wang, Cong-Cong; Li, Yan-Bin; Dou, Ying-Chun; Duan, Rui-Sheng

    2016-01-01

    Background Previously, we have demonstrated that spleen-derived dendritic cells (DCs) modified with atorvastatin suppressed immune responses of experimental autoimmune myasthenia gravis (EAMG). However, the effects of exosomes derived from atorvastatin-modified bone marrow DCs (BMDCs) (statin-Dex) on EAMG are still unknown. Methods Immunophenotypical characterization of exosomes from atorvastatin- and dimethylsulfoxide (DMSO)-modified BMDCs was performed by electron microscopy, flow cytometry...

  2. Effects of adrenalectomy on radiation changes in thymo-lymphatic organs of mice

    International Nuclear Information System (INIS)

    In the present study, the effects of adrenalectomy upon the irradiation damage in the thymo-lymphatic organs were investigated. Young adult CF No. 1 male mice were used as experimental animals. The mice were divided into three groups: the first group received 300 R of total body X-irradiation immediately after bilateral adrenalectomy, the second group received only 300 R of total body X-irradiation and the third group was kept as nontreated controls. The experimental animals were killed at 2, 4, 6 and 24 hours after the X-irradiation. The weight of the thymo-lymphatic organs was precisely measured. Lymphocyte nuclei in smears of the thymus and of the mesenteric lymph node were stained with hematoxylin or fast green FCF, and the number of irradiation damaged cells were counted. The damaged cells were observed to be homogeneous in hematoxylin staining and cresent shaped in fast green staining. Changes in organ weight and damaged cell count were compared between these three groups. The loss in organ weight was less in the adrenalectomized irradiated mice than in animals given irradiation alone. The damaged cell count was significantly less in the adrenalectomized irradiated mice only at 2 hours after the irradiation. These findings were also confirmed by histological sections. Damaged cells were phagocytized by macrophages at 6 hours after the treatment, and most of the cell debris was gone by 24 hours after the treatment, suggesting the digestion of dead cells by macrophages. These findings indicate that the adrenalectomy may modify the effect of total body irradiation at the early stage after irradiation. (author)

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

    Science.gov (United States)

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

    2015-08-01

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

  4. Spatio-temporal changes of lymphatic contractility and drainage patterns following lymphadenectomy in mice.

    Directory of Open Access Journals (Sweden)

    Sunkuk Kwon

    Full Text Available OBJECTIVE: To investigate the redirection of lymphatic drainage post-lymphadenectomy using non-invasive near-infrared fluorescence (NIRF imaging, and to subsequently assess impact on metastasis. BACKGROUND: Cancer-acquired lymphedema arises from dysfunctional fluid transport after lymphadenectomy performed for staging and to disrupt drainage pathways for regional control of disease. However, little is known about the normal regenerative processes of the lymphatics in response to lymphadenectomy and how these responses can be accelerated, delayed, or can impact metastasis. METHODS: Changes in lymphatic "pumping" function and drainage patterns were non-invasively and longitudinally imaged using NIRF lymphatic imaging after popliteal lymphadenectomy in mice. In a cohort of mice, B16F10 melanoma was inoculated on the dorsal aspect of the paw 27 days after lymphadenectomy to assess how drainage patterns affect metastasis. RESULTS: NIRF imaging demonstrates that, although lymphatic function and drainage patterns change significantly in early response to popliteal lymph node (PLN removal in mice, these changes are transient and regress dramatically due to a high regenerative capacity of the lymphatics and co-opting of collateral lymphatic pathways around the site of obstruction. Metastases followed the pattern of collateral pathways and could be detected proximal to the site of lymphadenectomy. CONCLUSIONS: Both lymphatic vessel regeneration and co-opting of contralateral vessels occur following lymphadenectomy, with contractile function restored within 13 days, providing a basis for preclinical and clinical investigations to hasten lymphatic repair and restore contractile lymphatic function after surgery to prevent cancer-acquired lymphedema. Patterns of cancer metastasis after lymphadenectomy were altered, consistent with patterns of re-directed lymphatic drainage.

  5. Lymphatic filariasis in Brazil: epidemiological situation and outlook for elimination

    Directory of Open Access Journals (Sweden)

    Fontes Gilberto

    2012-11-01

    Full Text Available Abstract Since the World Health Assembly’s (Resolution WHA 50.29, 1997 call for the elimination of lymphatic filariasis by the year 2020, most of the endemic countries identified have established programmes to meet this objective. In 1997, a National Lymphatic Filariasis Elimination Plan was drawn up by the Ministry of Health of Brazil, creating local programs for the elimination of Bancroftian filariasis in areas with active transmission. Based on a comprehensive bibliographic search for available studies and reports of filariasis epidemiology in Brazil, current status of this parasitic infection and the outlook for its elimination in the country were analysed. From 1951 to 1958 a nationwide epidemiological study conducted in Brazil confirmed autochthonous transmission of Bancroftian filariasis in 11 cities of the country. Control measures led to a decline in parasite rates, and in the 1980s only the cities of Belém in the Amazonian region (Northern region and Recife (Northeastern region were considered to be endemic. In the 1990s, foci of active transmission of LF were also described in the cities of Maceió, Olinda, Jaboatão dos Guararapes, and Paulista, all in the Northeastern coast of Brazil. Data provide evidence for the absence of microfilaremic subjects and infected mosquitoes in Belém, Salvador and Maceió in the past few years, attesting to the effectiveness of the measures adopted in these cities. Currently, lymphatic filariasis is a public health problem in Brazil only in four cities of the metropolitan Recife region (Northeastern coast. Efforts are being concentrated in these areas, with a view to eliminating the disease in the country.

  6. Unpredictability of lymphatic drainage patterns in melanoma patients.

    Science.gov (United States)

    Statius Muller, Markwin G; Hennipman, Feitse A; van Leeuwen, Paul A M; Pijpers, Rik; Vuylsteke, Ronald J; Meijer, Sybren

    2002-02-01

    We analysed the localisations of sentinel nodes (SN) found with the SN procedure to compare these sites with those that would have been predicted by conventional clinical descriptions of cutaneous lymphatic drainage. We assessed the surplus value of performing the SN procedure in melanoma patients who underwent regional nodal surgery. The SN procedure was performed in 348 patients with melanomas who were referred to our institute between 1993 and 1999. The localisations of the melanomas with the corresponding SNs were meticulously recorded on drawings of the human body and grouped according to the conventional descriptions. Predictability of lymph drainage was defined as the percentage of melanomas whose draining pattern was to the ipsilateral nearest basin, without simultaneous drainage to other basins or to an interval node. In all patients the SN procedure visualised at least one SN. We found 410 lymphatic basins in 347 patients. These basins included basins that could not have been predicted by the conventional clinical descriptions, such as multiple basins and contralateral drainage sites. For the head/neck region, SNs could be found in any of the basins described in the literature. The trunk's drainage predictability depended strongly on the melanoma localisation, ranging from 0% in the midline to 92% in one of the upper quadrants. The lower extremities had a high predictability of almost 100%, and predictability of drainage for the upper extremities ranged from 77% to 100%. In total, 34% of the patients had a cutaneous lymphatic drainage that was unpredictable, either totally or partially. We therefore conclude that an SN procedure is indispensable if the drainage site(s) are to be accurately identified. PMID:11930886

  7. Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration Los suplementos de ácidos grasos omega 3 tienen efectos beneficiosos en colitis ulcerosa a pesar del aumento de la infiltracción por neutrófilos del colon

    Directory of Open Access Journals (Sweden)

    Ioannis Varnalidis

    2011-10-01

    Full Text Available Purpose: omega 3 polyunsaturated fatty acids have anti-inflammatory properties and can be beneficial in the treatment of inflammatory diseases, such as ulcerative colitis. Dextran sodium sulphate (DSS colitis in rats appears to mimic nearly all of the morphological characteristics and lesion distributions of ulcerative colitis. The purpose of the current study was to investigate the efficacy of omega 3 fatty acids in the treatment of experimental ulcerative colitis. Methods: thirty-six Wistar rats were randomly assigned to group A or group B receiving 5% dextran sulfate sodium (DSS in their drinking water for eight days. For the next eight days post-DSS, group A animals received tap-water, and group B animals were fed a nutritional solution containing high levels of omega 3 polyunsaturated fatty acids (ProSure®, Abbott Laboratories, Zwolle, Netherlands once per day, administrated with a orogastric feeding tube. Results: animals fed an omega 3 rich diet exhibited a statistically significant increase in hematocrit and hemoglobin levels, compared to animals drinking tap water, and a trend towards histopathological and clinical improvement, with the administration of omega 3 fatty acids ameliorating epithelial erosion by day 8 post-DSS, but no statistically significant difference was observed between group A and group B animals at 4 or 8 days post-DSS. Also, a statistically significant increase in neutrophil infiltration was observed, as depicted by myelohyperoxidase activity. Conclusion: our findings support a positive role of omega 3 polyunsaturated fatty acids supplementation in an experimental model of ulcerative colitis despite the increased colonic neutrophil infiltration. Further studies are needed in order to investigate the role of increased neutrophils in colonic mucosa.

  8. The history of the elimination of lymphatic filariasis in China

    OpenAIRE

    De-jian, Sun; Xu-li, Deng; Ji-hui, Duan

    2013-01-01

    China used to be one of the most heavily endemic countries for lymphatic filariasis (LF) in the world. There were 864 endemic counties/cities in 16 provinces/autonomous regions/municipalities (P/A/M) with a total population of 330 million at risk of infection. Since the founding of the People’s Republic of China in 1949, the Chinese Government has designated the control of the disease to be a top priority. Due to decades of sustained efforts, close cooperation related to LF control among gove...

  9. Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling.

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); S.J. de Vlas (Sake); J.D.F. Habbema (Dik)

    2006-01-01

    textabstractMathematical simulation models for transmission and control of lymphatic filariasis are useful tools for studying the prospects of lymphatic filariasis elimination. Two simulation models are currently being used. The first, EPIFIL, is a population-based, deterministic model that simulate

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

    Science.gov (United States)

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

    2005-12-01

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

  11. IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

    DEFF Research Database (Denmark)

    Hammer, Troels; Tritsaris, Katerina; Hübschmann, Martin V;

    2009-01-01

    IL-20 is an arteriogenic cytokine that remodels collateral networks in vivo, and plays a role in cellular organization. Here, we investigate its role in lymphangiogenesis using a lymphatic endothelial cell line, hTERT-HDLEC, which expresses the lymphatic markers LYVE-1 and podoplanin. Upon stimul...

  12. EVALUATION OF MASS DRUG ADMINISTRATION FOR ELIMINATION OF LYMPHATIC FILARIASIS IN GUNTUR DISTRICT, ANDHRA PRADESH

    OpenAIRE

    Purnamma; Neelima,

    2015-01-01

    BACKGROUND : Lymphatic Filariasis (LF) is a serious Socio Economic and Public Health problem in the world. In India, it is estimated that 554.2 million populations are at risk of Lymphatic Filariasis infection, in 243 implementation units (Districts). National Health Policy, 2002 aims at elimination of transmission and prevention of disability ...

  13. The Elimination of Lymphatic Filariasis: A Strategy for Poverty Alleviation and Sustainable Development – Perspectives from the Philippines

    OpenAIRE

    Galvez Tan, Jaime Z

    2003-01-01

    Background Within the Philippines areas endemic for lymphatic filariasis are in regions with the highest incidence of poverty. Out of a total of 79 provinces, 39 have a higher poverty incidence than the national average and 30 of these 39 provinces are endemic for lymphatic filariasis. Discussion Recognizing that provinces endemic for lymphatic filariasis (LF) are also the poorest provinces, the elimination of lymphatic filariasis in these areas presents significant opportunities to reduce po...

  14. The argument for integrating vector control with multiple drug administration campaigns to ensure elimination of lymphatic filariasis

    OpenAIRE

    Burkot, TR; Durrheim, DN; Melrose, WD; Speare, R.; Ichimori, K.

    2006-01-01

    Background There is a danger that mass drug administration campaigns may fail to maintain adequate treatment coverage to achieve lymphatic filariasis elimination. Hence, additional measures to suppress transmission might be needed to ensure the success of the Global Program for the Elimination of Lymphatic Filariasis. Discussion Vector control successfully eliminated lymphatic filariasis when implemented alone or with mass drug administration. Challenges to lymphatic filariasis elimination in...

  15. Indocyanine Green Lymphographic Signs of Lymphatic Collateral Formation in Lower Extremity Lymphedema After Cancer Resection.

    Science.gov (United States)

    Tashiro, Kensuke; Shibata, Takashi; Mito, Daisuke; Ishiura, Ryohei; Kato, Motoi; Yamashita, Shuji; Narushima, Mitsunaga; Iida, Takuya; Koshima, Isao

    2016-08-01

    Indocyanine green lymphography has recently been used to assess lymphatic vessel function in lymphedema patients. Postoperative collateral lymphatic vessels toward ipsilateral axillary lymph nodes are rarely seen above the umbilical level in lower lymphedema patients. Between January 2012 and December 2014, we performed indocyanine green lymphography of 192 limbs in 96 lower extremity lymphedema cases. As a result, dermal back flow appeared in 95 cases, with 38 in the lower abdominal area and 31 in the genital area. We confirmed 3 cases of superficial lymphatic collateral ways extending above the umbilical level to the axillary lymph nodes. All 3 cases had similarity in lower abdominal edema, so excessive lymphatic fluid in the lower abdomen was assumed to be the cause. Lymphatic collateral ways from abdomen to axillary lymph nodes in this study was likely to be designed to prevent the progress of lymphedema. PMID:26418772

  16. Effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats

    Institute of Scientific and Technical Information of China (English)

    Zuoli Xia; Baoling Sun; Mingfeng Yang; Dongmei Hu; Tong Zhao; Jingzhong Niu

    2006-01-01

    BACKGROUND: It has been shown that although brain does not contain lining endothelial lymphatic vessel,it has lymphatic drain.Anterior lymphatic vessel in brain tissue plays a key role in introducing brain interstitial fluid to lymphatic system;however,the significance of lymphatic drain and the affect on cerebral edema remains unclear.OBJECTIVE: To investigate the effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats.DESIGN: Randomized controlled animal study.SETTING: Institute of Cerebral Microcirulation of Taishan Medical College and Department of Neurology of Affiliated Hospital.MATERIALS:A total of 63 healthy adult male Wistar rats weighing 300-350 g were selected in this study.Forty-seven rats were used for the morphological observation induced by lymphatic drain and randomly divided into three groups:general observation group(n=12),light microscopic observation group(n=21)and electronic microscopic observation group(n=14).The rats in each group were divided into cerebral lymphatic block subgroup and sham-operation control subgroup.Sixteen rats were divided into cerebral the effect of cerebral lymphatic block on cortical evoked potential,in which the animals were randomly divided into sham-operation group(n=6)and cerebral lymphatic block group(n=10).METHODS:The experiment was carried out in the Institute of Cerebral Microcirculation of Taishan Medical College from January to August 2003.Rats in cerebral lymphatic block group were anesthetized and separated bilateral superficial and deep cervical lymph nodes under sterile condition. Superior and inferior boarders of lymph nodes were ligated the inputting and outputting channels, respectively, and then lymph node was removed so as to establish cerebral lymphatic drain disorder models. Rats in sham-operation control group were not ligated the lymphatic vessel and removed lymph nodes.and other operations were as the same as those in cerebral lymphatic block group

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

    Directory of Open Access Journals (Sweden)

    Kim Wun-Jae

    2011-04-01

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

  18. Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy.

    Directory of Open Access Journals (Sweden)

    Makoto Mihara

    Full Text Available INTRODUCTION: To date, an electron microscopy study of the collecting lymphatic vessels has not been conducted to examine the early stages of lymphedema. However, such histological studies could be useful for elucidating the mechanism of lymphedema onset. The aim of this study was to clarify the changes occurring in collecting lymphatic vessels after lymphadenectomy. METHODS: The study was conducted on 114 specimens from 37 patients who developed lymphedema of the lower limbs after receiving surgical treatment for gynecologic cancers and who consulted the University of Tokyo Hospital and affiliated hospitals from April 2009 to March 2011. Lymphatic vessels that were not needed for lymphatico venous anastomosis surgery were trimmed and subsequently examined using electron microscopy and light microscopy. RESULTS: Based on macroscopic findings, the histochemical changes in the collecting lymphatic vessels were defined as follows: normal, ectasis, contraction, and sclerosis type (NECST. In the ectasis type, an increase in endolymphatic pressure was accompanied by a flattening of the lymphatic vessel endothelial cells. In the contraction type, smooth muscle cells were transformed into synthetic cells and promoted the growth of collagen fibers. In the sclerosis type, fibrous elements accounted for the majority of the components, the lymphatic vessels lost their transport and concentrating abilities, and the lumen was either narrowed or completely obstructed. CONCLUSIONS: The increase in pressure inside the collecting lymphatic vessels after lymphadenectomy was accompanied by histological changes that began before the onset of lymphedema.

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

    Science.gov (United States)

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

    2015-06-29

    The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. PMID:26077718

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

    Science.gov (United States)

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

    2015-06-29

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

  1. Eicosanoid production and lymphatic responsiveness in human cigarette smokers compared with non-smokers.

    Science.gov (United States)

    Sinzinger, H; Kaliman, J; Oguogho, A

    2000-03-01

    Leg lymphatic segments were isolated from 10 patients (4 cigarette smokers and 6 non-smokers) undergoing conventional lymphography. Prostaglandin (PG) levels and PG synthesis in the lymphatics and in a variety of body fluids and the effects of eicosanoids on lymphatic contractility were determined. Leg lymphatics from 4 smokers generated less PGI2 and contained more 8-epi-PGF2 alpha when compared with leg lymphatics in 6 non-smokers. Similarly, levels of 8-epi-PGF2 alpha in smokers compared with non-smokers were higher in plasma (28.6 cf 19.7 pg/ml), leg lymph (146.7 cf 65.3 pg/ml), serum (299.0 cf 204.1 pg/ml), and urine (473.4 cf 241.0 pg/mg creatinine). Lymphatics from smokers also showed a higher contractile response, less 14C-arachidonic acid conversion to PGI2 and less PGI2-formation with various stimuli compared with non-smokers. Together these findings suggest that smoking induces oxidation injury, promotes altered (iso-)eicosanoid production and impacts on the function and dysfunction of peripheral lymphatics under normal circumstances and in a variety of clinical disorders. PMID:10769813

  2. Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment.

    Directory of Open Access Journals (Sweden)

    Jarish N Cohen

    Full Text Available Peripheral self-tolerance eliminates lymphocytes specific for tissue-specific antigens not encountered in the thymus. Recently, we demonstrated that lymphatic endothelial cells in mice directly express peripheral tissue antigens, including tyrosinase, and induce deletion of specific CD8 T cells via Programmed Death Ligand-1 (PD-L1. Here, we demonstrate that high-level expression of peripheral tissue antigens and PD-L1 is confined to lymphatic endothelial cells in lymph nodes, as opposed to tissue (diaphragm and colon lymphatics. Lymphatic endothelial cells in the lymph node medullary sinus express the highest levels of peripheral tissue antigens and PD-L1, and are the only subpopulation that expresses tyrosinase epitope. The representation of lymphatic endothelial cells in the medullary sinus expressing high-level PD-L1, which is necessary for normal CD8 T cell deletion kinetics, is controlled by lymphotoxin-β receptor signaling and B cells. Lymphatic endothelial cells from neonatal mice do not express high-level PD-L1 or present tyrosinase epitope. This work uncovers a critical role for the lymph node microenvironment in endowing lymphatic endothelial cells with potent tolerogenic properties.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Müller André

    2012-03-01

    Full Text Available Abstract Background The secretory leukocyte protease inhibitor (SLPI exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown Methods To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-β. Results The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-β and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. In vitro, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25hi CD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-β to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation. Conclusion In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.

  5. Triptolide ameliorates colonic fibrosis in an experimental rat model

    OpenAIRE

    Tao, Qingsong; Wang, Baochai; Zheng, Yu; Li, Guanwei; Ren, Jianan

    2015-01-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn’s disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2012-03-15

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

  8. 27 CFR 24.178 - Amelioration.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Amelioration. 24.178 Section 24.178 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... is calculated as tartaric acid for grapes, malic acid for apples, and citric acid for other...

  9. Biological effect of total lymphatic irradiation in cancer patients

    International Nuclear Information System (INIS)

    Fifteen cancer patients (1 with seminoma and 14 with malignant lymphoma) were given TLI(Total Lymphatic Irradiation) with 60Co γ-rays. Three cases received 6 Gy and 12 cases received 8 Gy, and the chromosome aberrations in peripheral blood lymphocytes were examined. It was estimated that a single TLI of 6 or 8 Gy would correspond to total body irradiation of averaged 3.78 or 4.3 Gy respectively. A course of moderate acute radiation symdrome with digestive tract reaction and hemopoietic and immunologic depession was observed clinically. WBC and platelets decreased rapidly. Lymphocytes changed both quantitatively and qualitatively at the early stage. Symptoms of acute radiation sickness subsided within 40 days. The severe complications were infection and hemorrhage. In the result, the tumours reduced in size or remitted completely. TLI seems to be a promising approach for the treatment of advenced malignant lymphomas. Further study of this treatment is needed

  10. The history of the elimination of lymphatic filariasis in China

    Science.gov (United States)

    2013-01-01

    China used to be one of the most heavily endemic countries for lymphatic filariasis (LF) in the world. There were 864 endemic counties/cities in 16 provinces/autonomous regions/municipalities (P/A/M) with a total population of 330 million at risk of infection. Since the founding of the People’s Republic of China in 1949, the Chinese Government has designated the control of the disease to be a top priority. Due to decades of sustained efforts, close cooperation related to LF control among government departments, and active participation of endemic populations, an all-round campaign for prevention and control has been carried out vigorously and successfully. Over many years, great achievements have been made through persistent endeavors of Chinese scientists and disease control workers. The ultimate goal to eliminate LF in the country was achieved in 2006. PMID:24289733

  11. Drug targets for lymphatic filariasis: A bioinformatics approach

    Directory of Open Access Journals (Sweden)

    Om Prakash Sharma

    2013-08-01

    Full Text Available This review article discusses the current scenario of the national and international burden due to lymphatic filariasis (LF and describes the active elimination programmes for LF and their achievements to eradicate this most debilitating disease from the earth. Since, bioinformatics is a rapidly growing field of biological study, and it has an increasingly significant role in various fields of biology. We have reviewed its leading involvement in the filarial research using different approaches of bioinformatics and have summarized available existing drugs and their targets to re-examine and to keep away from the resisting conditions. Moreover, some of the novel drug targets have been assembled for further study to design fresh and better pharmacological therapeutics. Various bioinformatics-based web resources, and databases have been discussed, which may enrich the filarial research.

  12. Mapping the geographical distribution of lymphatic filariasis in Zambia

    DEFF Research Database (Denmark)

    Mwase, Enala T; Stensgaard, Anna-Sofie; Nsakashalo-Senkwe, Mutale;

    2014-01-01

    BACKGROUND: Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control...... volunteers from 108 geo-referenced survey sites across Zambia were examined for circulating filarial antigens (CFA) with rapid format ICT cards, and a map indicating the distribution of CFA prevalences in Zambia was prepared. 78% of survey sites had CFA positive cases, with prevalences ranging between 1...... to be an important determinant of medium-high prevalence levels. CONCLUSIONS/SIGNIFICANCE: LF was found to be surprisingly widespread in Zambia, although in most places with low prevalence. The produced maps and the identified environmental correlates of LF infection will provide useful guidance for planning...

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

    International Nuclear Information System (INIS)

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

  14. Phytoceramide Shows Neuroprotection and Ameliorates Scopolamine-Induced Memory Impairment

    Directory of Open Access Journals (Sweden)

    Seikwan Oh

    2011-10-01

    Full Text Available The function and the role phytoceramide (PCER and phytosphingosine (PSO in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o. recovered the scopolamine-induced reduction in step-through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

  15. Coxsackie- and adenovirus receptor (CAR) is expressed in lymphatic vessels in human skin and affects lymphatic endothelial cell function in vitro

    International Nuclear Information System (INIS)

    Lymphatic vessels play an important role in tissue fluid homeostasis, intestinal fat absorption and immunosurveillance. Furthermore, they are involved in pathologic conditions, such as tumor cell metastasis and chronic inflammation. In comparison to blood vessels, the molecular phenotype of lymphatic vessels is less well characterized. Performing comparative gene expression analysis we have recently found that coxsackie- and adenovirus receptor (CAR) is significantly more highly expressed in cultured human, skin-derived lymphatic endothelial cells (LECs), as compared to blood vascular endothelial cells. Here, we have confirmed these results at the protein level, using Western blot and FACS analysis. Immunofluorescence performed on human skin confirmed that CAR is expressed at detectable levels in lymphatic vessels, but not in blood vessels. To address the functional significance of CAR expression, we modulated CAR expression levels in cultured LECs in vitro by siRNA- and vector-based transfection approaches. Functional assays performed with the transfected cells revealed that CAR is involved in distinct cellular processes in LECs, such as cell adhesion, migration, tube formation and the control of vascular permeability. In contrast, no effect of CAR on LEC proliferation was observed. Overall, our data suggest that CAR stabilizes LEC-LEC interactions in the skin and may contribute to lymphatic vessel integrity

  16. Surveillance of lymphatic filariasis 5 years after stopping mass drug administration in Menoufiya Governorate, Egypt.

    Science.gov (United States)

    Moustafa, M A; Thabet, H S; Saad, G A; El-Setouhy, M; Mehrez, M; Hamdy, D M

    2014-05-01

    The World Health Organization recommends that before lymphatic filariasis elimination in an area can be confirmed, an additional survey should be performed at least 5 years after stopping mass drug administration. The current study aimed to determine the status of lymphatic filariasis 5 years after cessation ofthe mass drug administration in 3 sentinel Egyptian villages in Menoufiya Governorate. The rapid immunochromatographic card test (ICT) and a new commercial antibody detection kit (CELISA®) were used. All 1321 primary-school children aged 6-7 years old were ICT negative but 27 children were antibody positive. All households surveyed in one village with the highest antibody prevalence were ICT negative, indicating an absence of lymphatic filariasis. The CELISA antibody kit needs more standardization and development to be useful under field conditions. We conclude that lymphatic filariasis is no longer a public health problem in these villages and other villages with similar epidemiological conditions.

  17. Mucosa-associated lymphatic tissue lymphoma of the lower lip in a child.

    Science.gov (United States)

    Bombeccari, Gian Paolo; Guzzi, Gianpaolo; Ruffoni, Diego; Gianatti, Andrea; Mariani, Umberto; Spadari, Francesco

    2011-12-01

    Mucosa-associated lymphatic tissue lymphoma of the lip in a child is a very rare clinical entity whose cause is poorly understood. We describe an 11-year-old boy who presented with a 5-month history of an asymptomatic nodule on the lower lip with the clinical appearance of a benign mucocele. After surgical excision of the lower lip lesion, lymphocyte phenotypic analysis and histologic examination of the specimen disclosed an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphatic tissue type of the buccal minor salivary glands. Mucosa-associated lymphatic tissue lymphoma of the lip may clinically resemble a large mucocele. To prevent a delayed detection of lip mucosa-associated lymphatic tissue lymphoma, an incisional biopsy of large mucous cysts of the oral mucosa before marsupialization is recommended. PMID:22152894

  18. Surveillance of lymphatic filariasis 5 years after stopping mass drug administration in Menoufiya Governorate, Egypt.

    Science.gov (United States)

    Moustafa, M A; Thabet, H S; Saad, G A; El-Setouhy, M; Mehrez, M; Hamdy, D M

    2014-05-01

    The World Health Organization recommends that before lymphatic filariasis elimination in an area can be confirmed, an additional survey should be performed at least 5 years after stopping mass drug administration. The current study aimed to determine the status of lymphatic filariasis 5 years after cessation ofthe mass drug administration in 3 sentinel Egyptian villages in Menoufiya Governorate. The rapid immunochromatographic card test (ICT) and a new commercial antibody detection kit (CELISA®) were used. All 1321 primary-school children aged 6-7 years old were ICT negative but 27 children were antibody positive. All households surveyed in one village with the highest antibody prevalence were ICT negative, indicating an absence of lymphatic filariasis. The CELISA antibody kit needs more standardization and development to be useful under field conditions. We conclude that lymphatic filariasis is no longer a public health problem in these villages and other villages with similar epidemiological conditions. PMID:24952286

  19. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick [University of Oxford, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Science, Oxford (United Kingdom); Jackson, David [Weatherall Institute of Molecular Medicine, Human Immunology Unit, Oxford (United Kingdom)

    2009-12-15

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  20. Evaluation of Wuchereria bancrofti GST as a Vaccine Candidate for Lymphatic Filariasis

    OpenAIRE

    Anandharaman Veerapathran; Gajalakshmi Dakshinamoorthy; Munirathinam Gnanasekar; Maryada Venkata Rami Reddy; Ramaswamy Kalyanasundaram

    2009-01-01

    BACKGROUND: Lymphatic filarial parasites survive within the lymphatic vessels for years despite the complex immune environment surrounding them. Parasites possibly accomplish this by adopting various immunomodulatory strategies, which include release of glutathione-S-transferases (GSTs) that counteract the oxidative free radicals produced by the host. Since GSTs produced by parasites appear to be critical for the survival of parasites in the host, several studies evaluated the potential of pa...

  1. Delimitation of lymphatic filariasis transmission risk areas: a geo-environmental approach

    OpenAIRE

    Sabesan, Shanmugavelu; Raju, Hari Kishan K; Srividya, AdiNarayanan; Pradeep Kumar DAS

    2006-01-01

    Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) depends upon Mass Drug Administration (MDA) to interrupt transmission. Therefore, delimitation of transmission risk areas is an important step, and hence we attempted to define a geo-environmental risk model (GERM) for determining the areas of potential transmission of lymphatic filariasis. Methods A range of geo-environmental variables has been selected, and customized on GIS platform to develop GERM for identifying th...

  2. Elimination of Lymphatic Filariasis: Mass Drug Administration in Endemic Areas of (Bidar District) Karnataka-2008

    OpenAIRE

    Ranganath, T. S.; N Ramakrishna Reddy

    2012-01-01

    Background : Lymphatic Filariasis is a mosquito transmitted disease, caused by parasitic worm Wuchereria bancrofti. Global Programme for Elimination of Lymphatic Filariasis was established in early 2000. The strategy recommended by the World Health Organization is annual Mass Drug Administration (MDA) of single-dose of Diethylcarbamazine 6 mg/kg (DEC), distributed to inhabitants of Filariasis endemic areas, excluding children below 2 years of age, pregnant women, and seriously ill persons, an...

  3. Issues in Delivering Morbidity Management for Lymphatic Filariasis Elimination: A Study in Pondicherry, South India

    OpenAIRE

    A. Krishna Kumari; Yuvaraj J; Das, L. K

    2012-01-01

    Lymphatic filariasis is a vector borne parasitic disease causing long term disability. The Global Programme to Eliminate Lymphatic Filariasis aims to achieve its objective through two strategies; Mass Drug Administration (MDA) to interrupt transmission and Morbidity Management (MM) to manage disability for those already affected. MDA is going on in full swing in endemic areas; but MM is lagging behind. An exploratory study was conducted in Pondicherry through focus group discussions to find o...

  4. Assessing Coverage of Mass Drug Administration against Lymphatic Filariasis in Gulbarga District, Karnataka

    OpenAIRE

    Anil NS

    2012-01-01

    Background: Lymphatic filariasis is an important public health problem in India not only due to morbid condition but also due to social stigma, sexual incapacitation and considerable economic loss. The Government of India in 2004 began a nationwide mass drug administration (MDA) campaign in all the known Lymphatic filariasis endemic districts with an annual single dose of Diethylcarbamazine citrate with the aim of eliminating it as a public health problem by the year 2015. Inspite...

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

    OpenAIRE

    Iboh Cletus I; Okon Okpok E; Opara Kenneth N; Asor Joseph E; Etim Susan E

    2012-01-01

    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...

  6. Modelling strategies to break transmission of lymphatic filariasis - aggregation, adherence and vector competence greatly alter elimination

    OpenAIRE

    Irvine, M. A.; Reimer, L.J.; Njenga, S. M; Gunawardena, S; Kelly-Hope, L; Bockarie, M.; Hollingsworth, T. D.

    2015-01-01

    Background With ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios. Methods We develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a firs...

  7. EVALUATION OF MASS DRUG ADMINISTRATION CAMPAIGN AGA INST LYMPHATIC FILARIASIS AT BIDAR DISTRICT

    OpenAIRE

    Mubeen; Sunil Kumar; Nigudgi; Shrinivas

    2013-01-01

    ABSTRACT: INTRODUCTION: - Lymphatic Filariasis is one of the important publi c health and socioeconomic problem faced by many developing coun tries in the world. It is endemic in 83 countries and nearly 120 million people are affecte d worldwide of whom about 40 million are incapacitated and disfigured by the disease. It is one of the world's leading causes of permanent and long-term disability. The National Health Policy 20 02 aims at Elimination of Lymphatic Fi...

  8. Lymphatic filariasis baseline survey in two sentinel sites of Ogun state, Nigeria

    OpenAIRE

    Okorie, Patricia Nkem; Davies, Emmanuel; Ogunmola, Olushola Omoniyi; Ojurongbe, Olusola; Saka, Yisa; Okoeguale, Bridget; Braide, Ekanem Ikpi

    2015-01-01

    Introduction In preparation for Mass Drug Administration by National Lymphatic Filariasis Elimination Programme, a baseline epidemiological investigation on lymphatic filariasis (LF) was conducted in two sentinel sites of Ogun State, Nigeria. The study was carried out in Ado-Odo Ota and Abeokuta South Local Government Areas (LGAs) to determine LF prevalence, microfilarial density and the abundance of Wucheraria bancrofti in the mosquito vectors. Methods Microscopic examination of thick blood ...

  9. Pathological Steps of Cancer-Related Lymphedema: Histological Changes in the Collecting Lymphatic Vessels after Lymphadenectomy

    OpenAIRE

    Mihara, Makoto; Hara, Hisako; Hayashi, Yohei; Narushima, Mitsunaga; Yamamoto, Takumi; Todokoro, Takeshi; Iida, Takuya; Sawamoto, Naoya; Araki, Jun; Kikuchi, Kazuki; Murai, Noriyuki; Okitsu, Taro; Kisu, Iori; Koshima, Isao

    2012-01-01

    Introduction To date, an electron microscopy study of the collecting lymphatic vessels has not been conducted to examine the early stages of lymphedema. However, such histological studies could be useful for elucidating the mechanism of lymphedema onset. The aim of this study was to clarify the changes occurring in collecting lymphatic vessels after lymphadenectomy. Methods The study was conducted on 114 specimens from 37 patients who developed lymphedema of the lower limbs after receiving su...

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

    Science.gov (United States)

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

    2013-10-15

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

  11. Diphtheria toxin–mediated ablation of lymphatic endothelial cells results in progressive lymphedema

    Science.gov (United States)

    Gardenier, Jason C.; Hespe, Geoffrey E.; Kataru, Raghu P.; Savetsky, Ira L.; Torrisi, Jeremy S.; Nores, Gabriela D. García; Dayan, Joseph J.; Chang, David; Zampell, Jamie; Martínez-Corral, Inés; Ortega, Sagrario; Mehrara, Babak J.

    2016-01-01

    Development of novel treatments for lymphedema has been limited by the fact that the pathophysiology of this disease is poorly understood. It remains unknown, for example, why limb swelling resulting from surgical injury resolves initially, but recurs in some cases months or years later. Finding answers for these basic questions has been hampered by the lack of adequate animal models. In the current study, we used Cre-lox mice that expressed the human diphtheria toxin receptor (DTR) driven by a lymphatic-specific promoter in order to noninvasively ablate the lymphatic system of the hind limb. Animals treated in this manner developed lymphedema that was indistinguishable from clinical lymphedema temporally, radiographically, and histologically. Using this model and clinical biopsy specimens, we show that the initial resolution of edema after injury is dependent on the formation of collateral capillary lymphatics and that this process is regulated by M2-polarized macrophages. In addition, we show that despite these initial improvements in lymphatic function, persistent accumulation of CD4+ cells inhibits lymphangiogenesis and promotes sclerosis of collecting lymphatics, resulting in late onset of edema and fibrosis. Our findings therefore provide strong evidence that inflammatory changes after lymphatic injury play a key role in the pathophysiology of lymphedema.

  12. Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability.

    Directory of Open Access Journals (Sweden)

    Xuefeng Zhang

    2012-01-01

    Full Text Available Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelope protein gp120 induced lymphatic hyperpermeability by disturbing the normal function of Robo4, a novel regulator of endothelial permeability. HIV-1 gp120 induced fibronectin expression and integrin α₅β₁ phosphorylation, which led to the complexing of these three proteins, and their subsequent interaction with Robo4 through its fibronectin type III repeats. Moreover, pretreatment with an active N-terminus fragment of Slit2, a Robo4 agonist, protected lymphatic endothelial cells from HIV-1 gp120-induced hyperpermeability by inhibiting c-Src kinase activation. Our results indicate that targeting Slit2/Robo4 signaling may protect the integrity of the lymphatic barrier and limit the dissemination of HIV in the host.

  13. Disrupted NOS signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow.

    Science.gov (United States)

    Datar, Sanjeev A; Gong, Wenhui; He, Youping; Johengen, Michael; Kameny, Rebecca J; Raff, Gary W; Maltepe, Emin; Oishi, Peter E; Fineman, Jeffrey R

    2016-07-01

    Associated abnormalities of the lymphatic circulation are well described in congenital heart disease. However, their mechanisms remain poorly elucidated. Using a clinically relevant ovine model of a congenital cardiac defect with chronically increased pulmonary blood flow (shunt), we previously demonstrated that exposure to chronically elevated pulmonary lymph flow is associated with: 1) decreased bioavailable nitric oxide (NO) in pulmonary lymph; and 2) attenuated endothelium-dependent relaxation of thoracic duct rings, suggesting disrupted lymphatic endothelial NO signaling in shunt lambs. To further elucidate the mechanisms responsible for this altered NO signaling, primary lymphatic endothelial cells (LECs) were isolated from the efferent lymphatic of the caudal mediastinal node in 4-wk-old control and shunt lambs. We found that shunt LECs (n = 3) had decreased bioavailable NO and decreased endothelial nitric oxide synthase (eNOS) mRNA and protein expression compared with control LECs (n = 3). eNOS activity was also low in shunt LECs, but, interestingly, inducible nitric oxide synthase (iNOS) expression and activity were increased in shunt LECs, as were total cellular nitration, including eNOS-specific nitration, and accumulation of reactive oxygen species (ROS). Pharmacological inhibition of iNOS reduced ROS in shunt LECs to levels measured in control LECs. These data support the conclusion that NOS signaling is disrupted in the lymphatic endothelium of lambs exposed to chronically increased pulmonary blood and lymph flow and may contribute to decreased pulmonary lymphatic bioavailable NO.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  15. Neuronal dysfunction with aging and its amelioration

    OpenAIRE

    Ando, Susumu

    2012-01-01

    The author focused on the functional decline of synapses in the brain with aging to understand the underlying mechanisms and to ameliorate the deficits. The first attempt was to unravel the neuronal functions of gangliosides so that gangliosides could be used for enhancing synaptic activity. The second attempt was to elicit the neuronal plasticity in aged animals through enriched environmental stimulation and nutritional intervention. Environmental stimuli were revealed neurochemically and mo...

  16. Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model

    Science.gov (United States)

    Kasuya, Akira; Sakabe, Jun-Ichi; Tokura, Yoshiki

    2014-02-01

    Ischemia-reperfusion (IR) injury is a cause of pressure ulcer. However, a mechanism underlying the IR injury-induced lymphatic vessel damage remains unclear. We investigated the alterations of structure and function of lymphatic ducts in a mouse cutaneous IR model. And we suggested a new method for evaluating the severity of pressure ulcer. Immunohistochemistry showed that lymphatic ducts were totally vanished by IR injury, while blood vessels were relatively preserved. The production of harmful reactive oxygen species (ROS) was increased in injured tissue. In vitro study showed a high vulnerability of lymphatic endothelial cells to ROS. Then we evaluated the impaired lymphatic drainage using an in vivo imaging system for intradermally injected indocyanine green (ICG). The dysfunction of ICG drainage positively correlated with the severity of subsequent cutaneous changes. Quantification of the lymphatic duct dysfunction by this imaging system could be a useful strategy to estimate the severity of pressure ulcer.

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

    OpenAIRE

    Cristina Thomas; Narahari, Saravu R.; Kuthaje S Bose; Kuthaje Vivekananda; Steven Nwe; West, Dennis P.; Mary Kwasny; Kundu, Roopal V

    2014-01-01

    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 psyc...

  18. Veins and Lymphatics is taking its first steps

    Directory of Open Access Journals (Sweden)

    Stefano Ricci

    2012-06-01

    Full Text Available Veins represent an important field of medicine. They are frequently involved in several diseases with a very wide range of severity. At one end of the spectrum, we have thrombosis and post-thrombotic syndrome, while at the other we have telangectasias, and a vast number of other conditions lie between these two extremes. Varicose veins are not always severe, but they affect an enormous number of people, with a consequent social and economic burden to society. Lymphology is also an important subject. Lymphatics play a role in many human diseases but lymphedema is a sort of Cinderella disease, neglected by patients, doctors and health care administrators. The name itself shows how little we know; a description of the clinical manifestation has been transformed into the name of the disease. Lymphedema is usually considered to be an inevitable event, be it congenital or secondary. Its incidence is thought to be growing each year, especially in poorer countries and in the field of oncology. Lymphedema treatment is mostly unsatisfactory and costs are high, while patient adherence to treatment is low...

  19. Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis.

    Science.gov (United States)

    Anugraha, G; Madhumathi, J; Prince, P R; Prita, P J Jeya; Khatri, V K; Amdare, N P; Reddy, M V R; Kaliraj, P

    2015-10-01

    Lymphatic filariasis, a mosquito-borne parasitic disease, affects more than 120 million people worldwide. Vaccination for filariasis by targeting different stages of the parasite will be a boon to the existing MDA efforts of WHO which required repeated administration of the drug to reduce the infection level and sustained transmission. Onset of a filaria-specific immune response achieved through antigen vaccines can act synergistically with these drugs to enhance the parasite killing. Multi-epitope vaccine approach has been proved to be successful against several parasitic diseases as it overcomes the limitations associated with the whole antigen vaccines. Earlier results from our group suggested the protective efficacy of multi-epitope vaccine comprising two immunodominant epitopes from Brugia malayi antioxidant thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2). In this study, the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes identified from our earlier study, was tested in a murine model (jird) of filariasis with L3 larvae. FEP conferred a significantly (P < 0.0001) high protection (69.5%) over the control in jirds. We also observed that the multi-epitope recombinant construct (FEP) induces multiple types of protective immune responses, thus ensuring the successful elimination of the parasite; this poses FEP as a potential vaccine candidate.

  20. Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis.

    Science.gov (United States)

    Anugraha, G; Madhumathi, J; Prince, P R; Prita, P J Jeya; Khatri, V K; Amdare, N P; Reddy, M V R; Kaliraj, P

    2015-10-01

    Lymphatic filariasis, a mosquito-borne parasitic disease, affects more than 120 million people worldwide. Vaccination for filariasis by targeting different stages of the parasite will be a boon to the existing MDA efforts of WHO which required repeated administration of the drug to reduce the infection level and sustained transmission. Onset of a filaria-specific immune response achieved through antigen vaccines can act synergistically with these drugs to enhance the parasite killing. Multi-epitope vaccine approach has been proved to be successful against several parasitic diseases as it overcomes the limitations associated with the whole antigen vaccines. Earlier results from our group suggested the protective efficacy of multi-epitope vaccine comprising two immunodominant epitopes from Brugia malayi antioxidant thioredoxin (TRX), several epitopes from transglutaminase (TGA) and abundant larval transcript-2 (ALT-2). In this study, the prophylactic efficacy of the filarial epitope protein (FEP), a chimera of selective epitopes identified from our earlier study, was tested in a murine model (jird) of filariasis with L3 larvae. FEP conferred a significantly (P < 0.0001) high protection (69.5%) over the control in jirds. We also observed that the multi-epitope recombinant construct (FEP) induces multiple types of protective immune responses, thus ensuring the successful elimination of the parasite; this poses FEP as a potential vaccine candidate. PMID:26179420

  1. Population migration: implications for lymphatic filariasis elimination programmes.

    Directory of Open Access Journals (Sweden)

    K D Ramaiah

    Full Text Available Human population migration is a common phenomenon in developing countries. Four categories of migration-endemic to nonendemic areas, rural to urban areas, non-MDA areas to areas that achieved lymphatic filariasis (LF control/elimination, and across borders-are relevant to LF elimination efforts. In many situations, migrants from endemic areas may not be able to establish active transmission foci and cause infection in local people in known nonendemic areas or countries. Urban areas are at risk of a steady inflow of LF-infected people from rural areas, necessitating prolonged intervention measures or leading to a prolonged "residual microfilaraemia phase." Migration-facilitated reestablishment of transmission in areas that achieved significant control or elimination of LF appears to be difficult, but such risk can not be excluded, particularly in areas with efficient vector-parasite combination. Transborder migration poses significant problems in some countries. Listing of destinations, in endemic and nonendemic regions/countries, and formulation of guidelines for monitoring the settlements and the infection status of migrants can strengthen the LF elimination efforts.

  2. Artificial lymphatic drainage systems for vascularized microfluidic scaffolds.

    Science.gov (United States)

    Wong, Keith H K; Truslow, James G; Khankhel, Aimal H; Chan, Kelvin L S; Tien, Joe

    2013-08-01

    The formation of a stably perfused microvasculature continues to be a major challenge in tissue engineering. Previous work has suggested the importance of a sufficiently large transmural pressure in maintaining vascular stability and perfusion. Here we show that a system of empty channels that provides a drainage function analogous to that of lymphatic microvasculature in vivo can stabilize vascular adhesion and maintain perfusion rate in dense, hydraulically resistive fibrin scaffolds in vitro. In the absence of drainage, endothelial delamination increased as scaffold density increased from 6 to 30 mg/mL and scaffold hydraulic conductivity decreased by a factor of 20. Single drainage channels exerted only localized vascular stabilization, the extent of which depended on the distance between vessel and drainage as well as scaffold density. Computational modeling of these experiments yielded an estimate of 0.40-1.36 cm H2O for the minimum transmural pressure required for vascular stability. We further designed and constructed fibrin patches (0.8 × 0.9 cm(2)) that were perfused by a parallel array of vessels and drained by an orthogonal array of drainage channels; only with the drainage did the vessels display long-term stability and perfusion. This work underscores the importance of drainage in vascularization, especially when a dense, hydraulically resistive scaffold is used. PMID:23281125

  3. Lymphatic drainage and CTV in carcinoma of the prostate.

    Science.gov (United States)

    Cellini, Numa; Luzi, Stefano; Mantini, Giovanna; Mattiucci, Gian Carlo; Morganti, Alessio G; Digesù, Cinzia; Bavasso, Antonella; Deodato, Francesco; Smaniotto, Daniela; Valentini, Vincenzo

    2003-01-01

    The prostate lymphatics drain into the periprostatic subcapsular network, from which 3 groups of ducts originate: the ascending ducts from the cranial prostate draining into the external iliac lymph nodes, the lateral ducts running to the hypogastric lymph nodes and the posterior ducts draining from the caudal prostate to the subaortic sacral lymph nodes of the promontory. Internal, external iliac and obturator lymph nodes are the most frequently involved by prostate carcinoma. Metastases to presacral and common iliac lymph nodes are rare. For the limited staging accuracy, present indications for seminal vesicle irradiation and pelvic node prohylactic irradiation are essentially based on risk categories and estimation algorithms; the latter while are widely used in international studies are not free of limitations as stressed since they were introduced. A method to deliver high doses to the tumor while limiting the irradiation of critical organs might be the delivery of a boost to the tumor only. This approach could become increasingly feasible with the diffusion of imaging procedures able to better define tumor extension. PMID:15018322

  4. Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema

    Science.gov (United States)

    Tan, I.-Chih; Maus, Erik A.; Rasmussen, John C.; Marshall, Milton V.; Fife, Caroline E.; Smith, Latisha A.; Sevick-Muraca, Eva M.

    2011-03-01

    Treatment of lymphatic disease is complicated and controversial, due in part to the limited understanding of the lymphatic system. Lymphedema (LE) is a frequent complication after surgical resection and radiation treatment in cancer survivors, and is especially debilitating in regions where treatment options are limited. Although some extremity LE can be effectively treated with manual lymphatic drainage (MLD) therapy or compression devices to direct proximal lymph transport, head and neck LE is more challenging, due to complicated geometry and complex lymphatic structure in head and neck region. Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, and to help direct MLD in a patient with head and neck LE. Immediately after 9 intradermal injections of 25 μg indocyanine green each around the face and neck region, NIR fluorescence images were collected using a custom-built imaging system with diffused excitation light illumination. These images were then used to direct MLD therapy. In addition, 3-dimensional (3D) surface profilometry was used to monitor response to therapy. NIR fluorescence images of functioning lymphatic vessels and abnormal structures were obtained. Precise geometries of facial structures were obtained using 3D profilometry, and detection of small changes in edema between therapy sessions was achieved. NIR fluorescence imaging provides a mapping of lymphatic architecture to direct MLD therapy and thus improve treatment efficacy in the head and neck LE, while 3D profilometry allowed longitudinal assessment of edema to evaluate the efficacy of therapy.

  5. Evaluation of water treatment sludge for ameliorating acid mine waste

    Energy Technology Data Exchange (ETDEWEB)

    Van Rensburg, L.; Morgenthal, T.L. [Potchefstroom University for Christian Higher Education, Potchefstroom (South Africa). School for Environmental Science & Development

    2003-10-01

    This study investigated the liming effect of water treatment sludge on acid mine spoils. The study was conducted with sludge from a water purification plant along the Vaal River catchments in South Africa. The optimum application rate for liming acid spoils and the speed and depth with which the sludge reacted with the mine waste were investigated. Chemical analysis indicated that the sludge is suitable as a liming agent because of its alkaline pH (8.08), high bicarbonate concentration (183.03 mg L{sup -1}), and low salinity (electrical conductivity = 76 mS m(-1)). The high cation exchange capacity of 15.47 cmol{sub c} kg{sup -1} and elevated nitrate concentration (73.16 mg L{sup -1}) also increase its value as an ameliorative material. The soluble concentrations for manganese, aluminum, lead, and selenium were high at a pH of 5 although only selenium (0.83 mg L{sup -1}) warranted some concern. According to experimental results, the application of 10 Mg ha{sup -1} of sludge to acid gold tailings increased the leach water pH from 4.5 to more than 7.5 and also increased the medium pH from 2.4 to 7.5. The addition of sludge further reduced the solubility of iron, manganese, copper, and zinc in the ameliorated gold tailings, but increased the electrical conductivity. The liming tempo was highest in the coal discard profile that had a coarse particle size distribution and took the longest to move through the gold tailings that had a fine particle size distribution. Results from this study indicate that the water treatment sludge investigated is suitable as a liming agent for rehabilitation of acid mine waste.

  6. Modelling lymphatic filariasis transmission and control: modelling frameworks, lessons learned and future directions.

    Science.gov (United States)

    Stolk, Wilma A; Stone, Chris; de Vlas, Sake J

    2015-03-01

    Mathematical modelling provides a useful tool for policy making and planning in lymphatic filariasis control programmes, by providing trend forecasts based on sound scientific knowledge and principles. This is now especially true, in view of the ambitious target to eliminate lymphatic filariasis as a public health problem globally by the year 2020 and the short remaining timeline to achieve this. To meet this target, elimination programmes need to be accelerated, requiring further optimization of strategies and tailoring to local circumstances. Insights from epidemiological transmission models provide a useful basis. Two general models of lymphatic filariasis transmission and control are nowadays in use to support decision-making, namely a population-based deterministic model (EPIFIL) and an individual-based stochastic model (LYMFASIM). Model predictions confirm that lymphatic filariasis transmission can be interrupted by annual mass drug administration (MDA), but this may need to be continued much longer than the initially suggested 4-6 years in areas with high transmission intensity or poor treatment coverage. However, the models have not been validated against longitudinal data describing the impact of MDA programmes. Some critical issues remain to be incorporated in one or both of the models to make predictions on elimination more realistic, including the possible occurrence of systematic noncompliance, the risk of emerging parasite resistance to anthelmintic drugs, and spatial heterogeneities. Rapid advances are needed to maximize the utility of models in decision-making for the ongoing ambitious lymphatic filariasis elimination programmes.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. [Some recent, or claiming to be recent, data on the superficial lymphatic circulation of the limbs].

    Science.gov (United States)

    Hidden, G

    1990-01-01

    Superficial collecting lymphatics of the limbs are present in much greater number than deep collecting vessels. There is practically no connexion between both networks. Although lymphatics are abundant distally, they tend to fuse toward the root of the limb. At certain "critical" points along their course, local aggression of the vessels may cause lymphedema. In the lower extremity, at the knee and thigh levels, the "critical" area takes the form of a narrow strip of adipose tissue along the path of the great saphenous vein. In the groin, danger is localized at the inferior superficial inguinal nodes, where the superficial collecting lymph vessels merge. In the upper limb, superficial lymphatics converge towards the base of the axilla, where they form three or four trunks that perforate the clavipectoral fascia, each penetrating through its own orifice. Draining lymphatics may approach the axillary space independently. Unfortunately, the inferior axillary nodes wherein they converge also drain the breast, as can be demonstrated by injecting different coloring materials concurrently in both areas. Excision of nodes draining the mammary gland unavoidably jeopardize superficial lymphatic drainage of the upper extremity.

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

    Science.gov (United States)

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

    2014-12-01

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

  10. Modelling lymphatic filariasis transmission and control: modelling frameworks, lessons learned and future directions.

    Science.gov (United States)

    Stolk, Wilma A; Stone, Chris; de Vlas, Sake J

    2015-03-01

    Mathematical modelling provides a useful tool for policy making and planning in lymphatic filariasis control programmes, by providing trend forecasts based on sound scientific knowledge and principles. This is now especially true, in view of the ambitious target to eliminate lymphatic filariasis as a public health problem globally by the year 2020 and the short remaining timeline to achieve this. To meet this target, elimination programmes need to be accelerated, requiring further optimization of strategies and tailoring to local circumstances. Insights from epidemiological transmission models provide a useful basis. Two general models of lymphatic filariasis transmission and control are nowadays in use to support decision-making, namely a population-based deterministic model (EPIFIL) and an individual-based stochastic model (LYMFASIM). Model predictions confirm that lymphatic filariasis transmission can be interrupted by annual mass drug administration (MDA), but this may need to be continued much longer than the initially suggested 4-6 years in areas with high transmission intensity or poor treatment coverage. However, the models have not been validated against longitudinal data describing the impact of MDA programmes. Some critical issues remain to be incorporated in one or both of the models to make predictions on elimination more realistic, including the possible occurrence of systematic noncompliance, the risk of emerging parasite resistance to anthelmintic drugs, and spatial heterogeneities. Rapid advances are needed to maximize the utility of models in decision-making for the ongoing ambitious lymphatic filariasis elimination programmes. PMID:25765197

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

    Directory of Open Access Journals (Sweden)

    Metcalfe Chris

    2010-05-01

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

  12. Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation.

    Science.gov (United States)

    Kesler, Cristina T; Pereira, Ethel R; Cui, Cheryl H; Nelson, Gregory M; Masuck, David J; Baish, James W; Padera, Timothy P

    2015-09-01

    The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 μm, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (∼60 μm). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability. PMID:25977256

  13. National mass drug administration costs for lymphatic filariasis elimination.

    Directory of Open Access Journals (Sweden)

    Ann S Goldman

    Full Text Available BACKGROUND: Because lymphatic filariasis (LF elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin, a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. METHODOLOGY/PRINCIPAL FINDINGS: To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1 the total annual cost of the LF program, 2 the average cost per person treated, and 3 the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1 the age (newness of the MDA program, 2 the use of volunteers, and 3 the size of the population treated. Substantial contributions by governments were documented - generally 60%-90% of program operation costs, excluding costs of donated medications. CONCLUSIONS/SIGNIFICANCE: MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.

  14. Transmission models and management of lymphatic filariasis elimination.

    Science.gov (United States)

    Michael, Edwin; Gambhir, Manoj

    2010-01-01

    The planning and evaluation of parasitic control programmes are complicated by the many interacting population dynamic and programmatic factors that determine infection trends under different control options. A key need is quantification about the status of the parasite system state at any one given timepoint and the dynamic change brought upon that state as an intervention program proceeds. Here, we focus on the control and elimination of the vector-borne disease, lymphatic filariasis, to show how mathematical models of parasite transmission can provide a quantitative framework for aiding the design of parasite elimination and monitoring programs by their ability to support (1) conducting rational analysis and definition of endpoints for different programmatic aims or objectives, including transmission endpoints for disease elimination, (2) undertaking strategic analysis to aid the optimal design of intervention programs to meet set endpoints under different endemic settings and (3) providing support for performing informed evaluations of ongoing programs, including aiding the formation of timely adaptive management strategies to correct for any observed deficiencies in program effectiveness. The results also highlight how the use of a model-based framework will be critical to addressing the impacts of ecological complexities, heterogeneities and uncertainties on effective parasite management and thereby guiding the development of strategies to resolve and overcome such real-world complexities. In particular, we underscore how this approach can provide a link between ecological science and policy by revealing novel tools and measures to appraise and enhance the biological controllability or eradicability of parasitic diseases. We conclude by emphasizing an urgent need to develop and apply flexible adaptive management frameworks informed by mathematical models that are based on learning and reducing uncertainty using monitoring data, apply phased or sequential

  15. Modelling co-infection with malaria and lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Hannah C Slater

    Full Text Available Malaria and lymphatic filariasis (LF continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change, and the associated timescale for such changes, as well as effects on the basic reproduction number R₀ of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings.

  16. Mapping the Geographical Distribution of Lymphatic Filariasis in Zambia

    Science.gov (United States)

    Mwase, Enala T.; Stensgaard, Anna-Sofie; Nsakashalo-Senkwe, Mutale; Mubila, Likezo; Mwansa, James; Songolo, Peter; Shawa, Sheila T.; Simonsen, Paul E.

    2014-01-01

    Background Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control, a country-wide mapping survey was undertaken between 2003 and 2011. Here the mapping activities are outlined, the findings across the numerous survey sites are presented, and the ecological requirements of the LF distribution are explored. Methodology/Principal findings Approximately 10,000 adult volunteers from 108 geo-referenced survey sites across Zambia were examined for circulating filarial antigens (CFA) with rapid format ICT cards, and a map indicating the distribution of CFA prevalences in Zambia was prepared. 78% of survey sites had CFA positive cases, with prevalences ranging between 1% and 54%. Most positive survey sites had low prevalence, but six foci with more than 15% prevalence were identified. The observed geographical variation in prevalence pattern was examined in more detail using a species distribution modeling approach to explore environmental requirements for parasite presence, and to predict potential suitable habitats over unsurveyed areas. Of note, areas associated with human modification of the landscape appeared to play an important role for the general presence of LF, whereas temperature (measured as averaged seasonal land surface temperature) seemed to be an important determinant of medium-high prevalence levels. Conclusions/significance LF was found to be surprisingly widespread in Zambia, although in most places with low prevalence. The produced maps and the identified environmental correlates of LF infection will provide useful guidance for planning and start-up of geographically targeted and cost-effective LF control in Zambia. PMID:24587466

  17. Means for limiting and ameliorating electrode shorting

    Energy Technology Data Exchange (ETDEWEB)

    Konynenburg, R.A. van; Farmer, J.C.

    1999-11-09

    A fuse and filter arrangement is described for limiting and ameliorating electrode shorting in capacitive deionization water purification systems utilizing carbon aerogel, for example. This arrangement limits and ameliorates the effects of conducting particles or debonded carbon aerogel in shorting the electrodes of a system such as a capacitive deionization water purification system. This is important because of the small interelectrode spacing and the finite possibility of debonding or fragmentation of carbon aerogel in a large system. The fuse and filter arrangement electrically protect the entire system from shutting down if a single pair of electrodes is shorted and mechanically prevents a conducting particle from migrating through the electrode stack, shorting a series of electrode pairs in sequence. It also limits the amount of energy released in a shorting event. The arrangement consists of a set of circuit breakers or fuses with one fuse or breaker in the power line connected to one electrode of each electrode pair and a set of screens of filters in the water flow channels between each set of electrode pairs.

  18. Means for limiting and ameliorating electrode shorting

    Energy Technology Data Exchange (ETDEWEB)

    Van Konynenburg, Richard A. (Livermore, CA); Farmer, Joseph C. (Tracy, CA)

    1999-01-01

    A fuse and filter arrangement for limiting and ameliorating electrode shorting in capacitive deionization water purification systems utilizing carbon aerogel, for example. This arrangement limits and ameliorates the effects of conducting particles or debonded carbon aerogel in shorting the electrodes of a system such as a capacitive deionization water purification system. This is important because of the small interelectrode spacing and the finite possibility of debonding or fragmentation of carbon aerogel in a large system. The fuse and filter arrangement electrically protect the entire system from shutting down if a single pair of electrodes is shorted and mechanically prevents a conducting particle from migrating through the electrode stack, shorting a series of electrode pairs in sequence. It also limits the amount of energy released in a shorting event. The arrangement consists of a set of circuit breakers or fuses with one fuse or breaker in the power line connected to one electrode of each electrode pair and a set of screens of filters in the water flow channels between each set of electrode pairs.

  19. Acetylcholinesterase inhibition ameliorates deficits in motivational drive

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2012-03-01

    Full Text Available Abstract Background Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes. Methods We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes. Results CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens. Conclusions Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.

  20. LYMPHATIC MAPPING AND SENTINEL LYMPH NODE BIOPSY IN THE PATIENTS WITH BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To identify the feasibility of the lymphatic mapping and sentinel node biopsy (SNB) in patients with breast cancer and to examine whether the characteristics of the sentinel lymph node (SLN) accurately predict the status of axillary node. Methods: 33 patients with breast cancer intraoperatively and postoperatively underwent a lymphatic mapping and the SNB using Patent Blue. Results: The SLNs were found in 30 of 33 patients (90.9%), the SLN accurately predicted the status of the axillary in 29 (96.7%). In one case the SLN was negative, but other axillary nodes were tumor positive. Conclusion: This study confirmed that the procedure of lymphatic mapping and SNB in the patients with breast cancer is feasibility, and that the histological characteristics of the SLN accurately predict the status of the axillary node. We believe that this technique might replace axillary lymph node dissection for breast cancer patients with negative axillae in the future.

  1. Are we nearly there yet? Coverage and compliance of mass drug administration for lymphatic filariasis elimination.

    Science.gov (United States)

    Alexander, Neal D E

    2015-03-01

    Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drug administration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for these coverage figures is the eligible, rather than total, population. By contrast, the 65% threshold, in the original modelling study, refers to ingestion of tablets in the total population. This corresponds to GPELF's use of 'epidemiological drug coverage' as a trigger for the Transmission Assessment Surveys (TAS), which indicate whether to proceed to post-MDA surveillance. The existence of less strict definitions of 'coverage' should not lead to premature TAS that could impair MDA's sustainability.

  2. Are we nearly there yet? Coverage and compliance of mass drug administration for lymphatic filariasis elimination.

    Science.gov (United States)

    Alexander, Neal D E

    2015-03-01

    Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drug administration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for these coverage figures is the eligible, rather than total, population. By contrast, the 65% threshold, in the original modelling study, refers to ingestion of tablets in the total population. This corresponds to GPELF's use of 'epidemiological drug coverage' as a trigger for the Transmission Assessment Surveys (TAS), which indicate whether to proceed to post-MDA surveillance. The existence of less strict definitions of 'coverage' should not lead to premature TAS that could impair MDA's sustainability. PMID:25575555

  3. Lymphatic fat absorption varies among rats administered dairy products differing in physiochemical properties

    DEFF Research Database (Denmark)

    Fruekilde, Maj-Britt; Høy, Carl-Erik

    2004-01-01

    We examined in rats the intestinal absorption of fat from dairy products differing in physiochemical properties. Five dairy products (cream cheese, cream, sour cream, butter, and mixed butter) with minor differences in fatty acid composition were administered by gavage to rats, and lymphatic fat...... absorption was examined. Absorption was followed for 8 h after administration of 300 mg fat from the dairy products. Administration of cream and sour cream resulted in faster lymphatic fat absorption than cream cheese, butter, and mixed butter, and at 8 h the accumulated absorption of fat was significantly...... higher. The lymphatic absorption of fat after cream cheese administration was similar to the absorption after butter and mixed butter administration up to the 4-h time point; then it increased to a level between that of rats administered cream or sour cream and butter or mixed butter. Overall...

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

    Science.gov (United States)

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

    2012-08-01

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

  5. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver- Re-evaluations of microlymphatic abnormalities

    Directory of Open Access Journals (Sweden)

    Yoshimura Kazunori

    2010-11-01

    Full Text Available Abstract Background From the morphological appearance, it was impossible to distinguish terminal portal venules from small lymphatic vessels in the portal tract even using histochemical microscopic techniques. Recently, D2-40 was found to be expressed at a high level in lymphatic endothelial cells (LECs. This study was undertaken to elucidate hepatic lymphatic vessels during progression of cirrhosis by examining the expression of D2-40 in LECs. Methods Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control and from cirrhotic livers (LC (Child A-LC and Child C-LC. Immunohistochemical (IHC, Western blot, and immunoelectron microscopic studies were conducted using D2-40 as markers for lymphatic vessels, as well as CD34 for capillary blood vessels. Results Imunostaining of D2-40 produced a strong reaction in lymphatic vessels only, especially in Child C-LC. It was possible to distinguish the portal venules from the small lymphatic vessels using D-40. Immunoelectron microscopy revealed strong D2-40 expression along the luminal and abluminal portions of the cell membrane of LECs in Child C-LC tissue. Conclusion It is possible to distinguish portal venules from small lymphatic vessels using D2-40 as marker. D2-40- labeling in lymphatic capillary endothelial cells is related to the degree of fibrosis in cirrhotic liver.

  6. Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

    Institute of Scientific and Technical Information of China (English)

    Masayuki Nagahashi; Yoshio Shirai; Toshifumi Wakai; Jun Sakata; Yoichi Ajioka; Katsuyoshi Hatakeyama

    2007-01-01

    AIM: To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders.METHODS: Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40,which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens,nine high-power (× 200) fields with the highest lymphatic vessel density (LVD), termed "hot spots", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). In individual hot spots,the LVD and relative lymphatic vessel area (LVA) were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses.RESULTS: In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2,35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively.Thus, both the LVD and LVA differed significantly (P <0.001 and P < 0.001, respectively; Kruskal-Wallis test)among the individual layers of the wall of the gallbladder,with the highest LVD and LVA values in the perimuscular connective tissue. Most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer.CONCLUSION: The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma.

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

    Directory of Open Access Journals (Sweden)

    Philipp Steven

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

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. Use of Coffee Pulp and Minerals for Natural Soil Ameliorant

    Directory of Open Access Journals (Sweden)

    Pujiyanto Pujiyanto

    2007-05-01

    Full Text Available In coffee plantation, solid waste of coffee pulp is usually collected as heap nearby processing facilities for several months prior being used as compost. The practice is leading to the formation of odor and liquid which contaminate the environment. Experiments to evaluate the effect of natural soil ameliorant derived from coffee pulp and minerals were conducted at The Indonesian Coffee and Cocoa Research Institute in Jember, East Java. The experiments were intended to optimize the use of coffee pulp to support farming sustainability and minimize negative impacts of solid waste disposal originated from coffee cherry processing. Prior to applications, coffee pulp was hulled to organic paste. The paste was then mixed with 10% minerals (b/b. Composition of the minerals was 50% zeolite and 50% rock phosphate powder. The ameliorant was characterized for their physical and chemical properties. Agronomic tests were conducted on coffee and cocoa seedling. The experiments were arranged according to Randomized Completely Design with 2 factors, consisted of natural ameliorant and inorganic fertilizer respectively. Natural ameliorant derived from coffee pulp was applied at 6 levels: 0, 30, 60, 90, 120 and 150 g dry ameliorant/seedling of 3 kg soil, equivalent to 0, 1, 2, 3, 4 and 5% (b/b of ameliorant respectively. Inorganic fertilizer was applied at 2 levels: 0 and 2 g fertilizer/application of N-P-K compound fertilizer of 15-15-15 respectively. The inorganic fertilizer was applied 4 times during nursery of coffee and cocoa. The result of the experiment indicated that coffee pulp may be used as natural soil ameliorant. Composition of ameliorant of 90% coffee pulp and 10% of minerals has good physical and chemical characteristics for soil amelioration. The composition has high water holding capacity; cations exchange capacity, organic carbon and phosphorus contents which are favorable to increase soil capacity to support plant growth. Application of

  11. Methods for effective fluorophore injection and imaging of lymphatics in small animals

    Science.gov (United States)

    DSouza, Alisha V.; Marra, Kayla A.; Gunn, Jason R.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2016-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully perform fluorescence imaging of IRDye®680RD in the lymphatics, in a repeatable manner.

  12. Computational lymphatic node models in pediatric and adult hybrid phantoms for radiation dosimetry.

    Science.gov (United States)

    Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E

    2013-03-01

    We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for

  13. Isoprostane 8-epi-prostaglandin F2 alpha is a potent contractor of human peripheral lymphatics.

    Science.gov (United States)

    Sinzinger, H; Oguogho, A; Kaliman, J

    1997-09-01

    Isoprostanes are products of free radical-catalyzed peroxidation and 8-epi-prostaglandin (PG) F2 alpha is the most important vasomodulator of this group of compounds. In human lower leg lymphatics isolated from 5 different patients without a smoking history or hyperlipidemia, 8-epi-PGF2 alpha stimulated in vitro contraction more strongly than the thromboxane receptor agonist U46619. Other isoprostanes (8-epi-PGE1, 8-epi-PGE2) had only limited lymphatic contractile potency. These data suggest a potentially relevant role for epi-8-PGF2 alpha in facilitating lymph transport especially in conditions of inflammation. PMID:9313207

  14. Direct lymphangiography as treatment option of lymphatic leakage: Indications, outcomes and role in patient's management

    Energy Technology Data Exchange (ETDEWEB)

    Gruber-Rouh, Tatjana, E-mail: tgruberrouh@googlemail.com [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Department of Radiology, Faculty of Medicine, Alexandria University, Alexandria (Egypt); Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany); Tsaur, Igor [Department of Urology, Johann Wolfgang Goethe University Frankfurt, Frankfurt am Main (Germany); Hammersting, Renate; Wichmann, Julian L.; Vogl, Thomas J.; Jacobi, Volkmar [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main (Germany)

    2014-12-15

    Background: To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. Method: This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10) underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Result: Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31), therapeutic lymphography was still successful in 58.1% of the patients. Conclusion: Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate.

  15. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

    OpenAIRE

    Joseph, SK; Ramaswamy, K.

    2013-01-01

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to...

  16. Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); Q.A. ten Bosch (Quirine); S.J. de Vlas (Sake); P.U. Fischer (Peter); G.J. Weil (Gary); A.S. Goldman (Ann)

    2013-01-01

    textabstractThe Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is neede

  17. Sentinel surveillance of Lymphatic filariasis, Schistosomiasis, Soil transmitted helminths and Malaria in rural southern Malawi

    NARCIS (Netherlands)

    K. Msyamboza; B. Ngwira; R. Banda; S. Mkwanda; B. Brabin

    2010-01-01

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

  18. LYMFASIM, a simulation model for predicting the impact of lymphatic filariasis control: quantification for African villages.

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); S.J. de Vlas (Sake); G.J.J.M. Borsboom (Gerard); J.D.F. Habbema (Dik)

    2008-01-01

    textabstractLYMFASIM is a simulation model for lymphatic filariasis transmission and control. We quantified its parameters to simulate Wuchereria bancrofti transmission by Anopheles mosquitoes in African villages, using a wide variety of reported data. The developed model captures the general epidem

  19. Polycystin Signaling Is Required for Directed Endothelial Cell Migration and Lymphatic Development

    Directory of Open Access Journals (Sweden)

    Patricia Outeda

    2014-05-01

    Full Text Available Autosomal dominant polycystic kidney disease is a common form of inherited kidney disease that is caused by mutations in two genes, PKD1 (polycystin-1 and PKD2 (polycystin-2. Mice with germline deletion of either gene die in midgestation with a vascular phenotype that includes profound edema. Although an endothelial cell defect has been suspected, the basis of this phenotype remains poorly understood. Here, we demonstrate that edema in Pkd1- and Pkd2-null mice is likely to be caused by defects in lymphatic development. Pkd1 and Pkd2 mutant embryos exhibit reduced lymphatic vessel density and vascular branching along with aberrant migration of early lymphatic endothelial cell precursors. We used cell-based assays to confirm that PKD1- and PKD2-depleted endothelial cells have an intrinsic defect in directional migration that is associated with a failure to establish front-rear polarity. Our studies reveal a role for polycystin signaling in lymphatic development.

  20. Lack of lymphangiogenesis in human primary cutaneous melanoma. Consequences for the mechanism of lymphatic dissemination.

    Science.gov (United States)

    de Waal, R. M.; van Altena, M. C.; Erhard, H.; Weidle, U. H.; Nooijen, P. T.; Ruiter, D. J.

    1997-01-01

    Cutaneous melanoma has an initial preference for lymphatic spread. Remarkably, melanoma progression toward this metastasizing phenotype is accompanied by intense blood vessel angiogenesis (hemangiogenesis), but lymphangiogenesis, the formation of new lymph vessels in the tumor, has never been reported. To investigate how primary melanoma cells interact with the existing lymphatic microvasculature, and whether lymphangiogenesis occurs, an immunostaining was developed that differentially decorates blood and lymph vessels in frozen tissue sections. The density and distribution of both these vessel types in and around thin ( or = 1.5 mm) primary melanoma lesions and in normal and uninvolved skin were determined. Although especially in thick melanoma lesions a significant increase in blood vessel density was observed, lymphatic density remained unaltered, showing that lymphangiogenesis did not occur. Morphological analysis indicated, however, that melanoma progression is accompanied by a sequence of events that involves hemangiogenesis supporting tumor expansion, especially in the vertical growth phase. Often, stromal sepia are formed around the blood capillaries in the tumor neovasculature protecting them from invasion. Lymph vessels inside the tumor were infrequently observed. However, subepidermal lymph vessels often seemed to be entrapped and penetrated by the expanding tumor mass. In this way, hemangiogenesis, as the driving force behind tumor expansion, might indirectly increase the chance of lymphatic invasion in the absence of lymphangiogenesis. This model explains the paradox that, although melanoma metastasis seems to require angiogenesis, a consistent relation of prognosis with blood capillary density in primary cutaneous melanoma is lacking. Images Figure 1 Figure 2 Figure 3 PMID:9176389

  1. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

    DEFF Research Database (Denmark)

    Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo;

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

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

    Science.gov (United States)

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

    2015-06-01

    Latest advances have brought to light the hypothesis that angiogenesis and lymphangiogenesis are tightly connected to some chronic inflammatory diseases. The present study focuses on immunohistochemical assessment of the quantitative changes in the blood and lymphatic microcirculatory bed in common chronic dermatosis - cutaneous lichen planus. Double immunohistochemistry with CD34 and podoplanin antibodies was used to detect blood and lymphatic endothelium, while anti-human VEGF was used for the observation of a key angiogenesis and lymphangiogenesis inducer. Morphometric analysis was performed with QuickPhoto Micro image analysis software. Results confirmed statistically significant enlargement of both the blood and lymphatic microcirculatory beds. Compared to healthy skin, cutaneous lichen planus lesions revealed 1.6 times enlarged blood microcirculatory bed and 1.8 times enlarged lymphatic microcirculatory bed. Vascular endothelial growth factor (VEGF) expression in lesional skin was significantly higher in the epidermis (19.1 times increase) than in the dermis (10.3 times increase). These findings indicate a tight association of angiogenesis and lymphangiogenesis with the pathogenesis of cutaneous lichen planus. PMID:25504638

  3. Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage

    DEFF Research Database (Denmark)

    Parving, H H; Hansen, J M; Nielsen, S L;

    1979-01-01

    of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain...

  4. IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression

    DEFF Research Database (Denmark)

    Nielsen, Sebastian Rune; Hammer, Troels; Gibson, Josefine;

    2013-01-01

    OBJECTIVE: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor-angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight into the ...

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

    Science.gov (United States)

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

    2014-09-01

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

  6. Lymphatic Fatty Acid Absorption Profile During 24 Hours After Administration of Triglycerides to Rats

    DEFF Research Database (Denmark)

    Porsgaard, Trine Charlotte; Straarup, Ellen Marie; Høy, Carl-Erik

    1999-01-01

    In this study we determined in rats the complete 24-h lymphatic fatty acid profile after administration of either rapeseedoil (RO) or rapeseed oil interesterified with 10:0 (RO/C10) with special emphasis on the transition from absorptive topostabsorptive phase. Rats were subjected to cannulation...

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

    Directory of Open Access Journals (Sweden)

    Miwa Sato

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

  8. Composition of the Extracellular Matrix of Lymphatic Novel Threadlike Structures: Is It Keratin?

    Directory of Open Access Journals (Sweden)

    Hyub Huh

    2013-01-01

    Full Text Available Background. The lumen of novel threadlike structures (NTSs is enclosed by a single layer of endothelial cells surrounded by extracellular matrix (ECM. We hypothesized that collagen may be a component of the ECM associated with lymphatic NTSs. Methods. Six female New Zealand white rabbits were anesthetized, and the NTS structures within lymphatic vessels were identified by contrast-enhanced stereomicroscopy or alcian blue staining. Isolated NTS specimens were stained with acridine orange, YOYO-1, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI. The structural and molecular composition of the ECM was investigated using transmission electron microscopy (TEM, electrospray ionization-mass spectrometry, and proteomic analysis. Results. The lymph vessel wall was stained red by DiI, and rod-shaped nuclei were stained green by YOYO-1. The area surrounding the NTS was also stained red and contained green rod-shaped nuclei. TEM images showed that the NTS consisted of many ECM fibers and the ECM fibers appeared to be ~100 nm in diameter and had narrowly spaced striated bands. Proteomic analysis of the lymphatic NTS-associated ECM identified 4 proteins: keratin 10, cytokeratin 3, cytokeratin 12, and soluble adenylyl cyclase. Conclusion. The TEM study suggested that the lymphatic NTS-associated ECM did not contain collagen. This was confirmed by proteomic analysis, which showed that keratin was the major component of the ECM.

  9. [Multiloculated mesenteric and retroperitoneal tumour - lymphatic malformation - in a 4-year-old girl].

    Science.gov (United States)

    Obuchowicz, Anna; Łoboda, Magdalena; Madziara, Wojciech; Jarecka, Beata

    2015-01-01

    Mesenteric cysts are rare and mostly benign abdominal tumours in children. Majority of them are lymphangiomas (lymphatic malformations). We diagnosed a broad, multiloculated mesenteric and retroperitoneal cyst, associated with intensive inflammation, in a 4-year-old girl. Surgical therapy was fully successful.

  10. Ameliorative effect of Morus alba leaves extract against developmental retinopathy in pups of diabetic and aluminum intoxicated pregnant albino rats

    Institute of Scientific and Technical Information of China (English)

    Hassan; El-Sayyed; Gamal; Badawy; Sobhy; Hassab; Elnabi; Ibrahim; El-Elaimy; Eman; Al; Shehari

    2015-01-01

    Objective: To investigate the possible ameliorative effect of crude water extract of Morus alba(M. alba) leaves on retinopathy of rat pups maternally subjected to diabetes and/or Al intoxication.Methods: Both control and experimental groups were subjected to certain integrated approaches, namely, biochemical assessments, light microscopic investigation, transmission electron microscopic investigation, single cell gel electrophoresis(comet assay) and determination of DNA fragmentation.Results: The retina of pups of diabetic and/or Al-intoxicated mothers exhibited abnormal alterations in retinal cell layers including retinal pigmented epithelium, photoreceptor inner segment and ganglion cells. Increased incidence of DNA fragmentation and apoptosis were evident in pups of diabetic and/or Al-intoxicated mothers. However, retina of pups maternally received M. alba extract plus diabetes or Al-intoxicated alone or in combination showed marked amelioration. Less degree of ameliorations was seen in retina of pups maternally subjected to combined treatment. Furthermore, application of crude water extract of M.alba resulted in amelioration of the alterations of maternal serum glucose as well as Al concentration.Conclusions: Based on the results of the present study, M. alba extract is effective against experimentally diabetic and Al-induced developmental retinopathy.

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Science.gov (United States)

    Kwon, Sunkuk; Price, Roger E

    2016-04-01

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

  14. Ameliorative property of Teucrium polium on second degree burn

    Directory of Open Access Journals (Sweden)

    Ansari Roya

    2013-01-01

    Full Text Available Introduction: Traditionally, burn wound healing activities have been claimed for Teucrium polium. Teucrium polium possesses antioxidant and inflammatory activities and seems to ameliorate burn wound healing. This study was performed to evaluate the effects of Teucrium polium on burn healing in Balb/C mice. Materials and Methods: In this preclinical experimental study 56 mice were randomly designated into 4 equal groups. Burn wounds were made using a hot plate with a surface area of 1.5 cm2. Animals were treated with Teucrium 2%, Silver sulfadiazine or Vaseline 2 times per day for 21 days. The forth group received no treatment. Results: The percentage of burn wounds healing and total time required for complete healing were evaluated and compared in different groups. Data were analyzed using ANOVA test. Conclusion: Teucrium extract accelerated the burn wound healing more rapidly than control groups (p<0.01. Teucrium polium is effective on burn wounds healing and might be beneficial in these groups of patients.

  15. Levels of eicosanoids (6-oxo-PGF1 alpha and 8-epi-PGF2 alpha) in human and porcine lymphatics and lymph.

    Science.gov (United States)

    Oguogho, A; Kaliman, J; Sinzinger, H

    1998-12-01

    Prostaglandin (PG)I2 is the primary eicosanoid synthesized by human lymphatics and 8-epi-PGF2 alpha, an isoprostane formed during free radical catalyzed peroxidation, is the most potent stimulator of lymphatic contraction tested thus far. We now examine the respective concentrations in the lymphatic wall of both human and porcine lymphatics and lymph fluid using specific immunoassays. Although both compounds are detectable in the lymphatic wall and lymph fluid, PGI2- (via its main metabolite 6-oxo-PGF1 alpha) is greater in the lymphatic wall whereas 8-epi-PGF2 alpha dominates in lymph fluid. Because inflammation is associated with oxidative injury, which in turn stimulates release of isoprostane, eicosanoid derivatives may modulate lymphatic tone during acute tissue reaction. PMID:9949390

  16. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    Science.gov (United States)

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S

    2016-02-12

    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes.

  17. Development of a Tissue-Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema.

    Science.gov (United States)

    Kanapathy, Muholan; Kalaskar, Deepak; Mosahebi, Afshin; Seifalian, Alexander M

    2016-03-01

    Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane (POSS-PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS-PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P PCU scaffold supports the attachment and growth of HDLECs. This study demonstrates the feasibility of developing a tissue-engineered lymphatic graft using the nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema. PMID:26517009

  18. Immunological characterization of recombinantWuchereria bancrofti cuticular collagen (COL-4) as putative vaccine candidate for human lymphatic filariasis

    Institute of Scientific and Technical Information of China (English)

    Chakkaravarthy Arunkumar; Pandurangan Pandiaraja; P. R. Prince; Perumal Kaliraj

    2014-01-01

    Objective:To elucidate immunoprophylactic potential of recombinantWuchereria bancrofti(W. bancrofti) cuticular collagen(COL-4) inBALB/c mice and filarial clinical samples.Methods:col-4 gene wasPCR amplified fromW. bancroftiL3 cDNA library and cloned in pRSETB vector. RecombinantCOL-4 was over expressed in salt inducible system and was purified by nickel affinity chromatography.Humoral and cellular responses were measured byELISA and peripheral blood mononuclear cells(PBMC) of various filarial clinical samples respectively using purified recombinantCOL-4 antigen.Then the protective immune responses ofCOL-4 immunizedBALB/c mice were characterized.Results:Sequence analysis ofCOL-4 with human host proteins reveals lack of homology.The recombinantCOL-4 was found to be at15 kDa fusion protein.The affinity purifiedCOL-4 showed significant reactivity with putatively immune sera and in a similar fashion it demonstrated marked proliferation inPBMC samples.Immunization studies in experimental filarial host(mice) elicited significant titers with protective antibody isotype profile(IgM and IgG).Cellular immune responses were also significant in terms of splenocytes proliferation assay on mice samples.Conclusions:Our immunological findings in experimental host suggestTh2 mediated immune response.Hence, we propose thatW. bancroftiCOL-4 could be an efficacious vaccine candidate against lymphatic filariasis.

  19. Role of RhoA in regulating the pump function of isolated lymphatics from hemorrhagic shock rats.

    Science.gov (United States)

    Si, Yong-Hua; Niu, Chun-Yu; Zhao, Zi-Gang; Zhang, Li-Min; Zhang, Yu-Ping

    2013-07-01

    The aim of this present study was to examine changes in RhoA protein levels and the role in RhoA in lymphatic contractility and reactivity after hemorrhagic shock. Levels of RhoA and phospho-RhoA in lymphatic tissue isolated from hemorrhagic shock rats were measured, and the contractility and reactivity to substance P of lymphatics isolated from control rats and rats subjected to shock 0.5 and 2 h were determined with an isolated lymphatic perfusion system at a transmural pressure of 3 cmH2O. At the same time, lymphatics isolated from rats subjected to shock 0.5 and 2 h were incubated with agonists and antagonists of RhoA/Rho kinase signaling. Contractile frequency, end-diastolic and end-systolic diameter, and passive diameter were recorded and used to calculate lymphatic tonic index, contractile amplitude, and fractional pump flow. After stimulation with a gradient of substance P, the differences between the preadministration and postadministration values of contractile frequency, contractile amplitude, tonic index, and fractional pump flow were calculated to further assess lymphatic reactivity. RhoA protein levels were significantly increased at 0.5 h after shock but decreased at 2 and 3 h after shock; p-Rho levels were initially increased after shock and subsequently decreased. The contractility and reactivity of 0.5-h-shocked lymphatics were significantly reduced by the RhoA antagonist C3 transferase and the Rho kinase antagonist Y-27632. The RhoA agonist U-46619 increased the contractility and reactivity of 2-h-shocked lymphatics, whereas Y-27632 suppressed the effect of U-46619. Okadaic acid, an inhibitor of myosin light-chain phosphatase, had no effect on the contractility of 2-h-shocked lymphatics, but improved lymphatic reactivity. These results suggest that RhoA is involved in the modulation of lymphatic pump function during hemorrhagic shock and that its effects may be mediated by Rho kinase and MLCP.

  20. Radiation Inactivation of Foot-and-Mouth Disease Virus in the Blood, Lymphatic Glands and Bone Marrow of the Carcasses of Infected Animals

    International Nuclear Information System (INIS)

    The FMD virus, like RP, SF and ASF viruses, is disseminated by infected animal products. The effects of gamma radiation on FMD virus cultures in vitro have been studied. According to these results, a dose of 3 Mrad when the virus is in the liquid state, and of 4 Mrad when it is in the dry state, is necessary to reduce the number of virus particles from 107 to 1. The D10 value for the liquid FMD virus is equivalent to 481 krad± the D10 value for the dried virus is equivalent to 626 krad. The effects of gamma radiation on FMD virus in situ have been studied. According to these results, to inactivate the FMD virus in the experimentally-infected pigs' tissues where the viral contents are the highest (blood, bone marrow, lymphatic glands), doses of 2 Mrad for the blood and bone marrow and of 1.5 Mrad for the lymphatic glands are necessary. Radiation may offer a possible means of reducing or eliminating the virus titre in many infected animal products and solve consequent quarantine problems. (author)

  1. Amelioration of safety management in infrastructure projects

    Directory of Open Access Journals (Sweden)

    Mr. Gopinath S.Mohite

    2014-11-01

    Full Text Available Accidents are a major public health concern, resulting in an estimated 1.2 million deaths and 50 million injuries worldwide each year specifically, the relationships between drivers' characteristics and road accidents are not fully understood. Many factors are involved in the accident occurrence at construction site. Some important elements that create a significant portion of accidents include: safety management error, poor training programs, human element, act of god, outdated procedure and no clear monitoring policy. Although some of these items are inevitable, but the occurrence of the largest part can be prevented. Therefore, for ameliorating the safety in a project each of these items should be analyzed and a practical approach introduced. In general, near miss, incident and accident are three dependent levels that mainly lead to injury. Risk and hazard are allocated in first level which means near miss, therefore, no on-time identification of hazard and risk causes to create incident and preventing accident in incident stage is unavoidable.

  2. Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

    Directory of Open Access Journals (Sweden)

    Iftekhar Hassan

    Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

  3. Relations of proliferative activities of gastric carcinoma cells to lymphatic involvement, venous invasion and prognosis

    Institute of Scientific and Technical Information of China (English)

    吴云飞; 徐惠绵; 陈峻青

    2004-01-01

    Background This study was to evaluate bivariate bromodeoxyuridine(BrdUrd)/DNA flow cytometric analysis in detection of gastric carcinoma and to study the relations of cellular BrdUrd labeling indices (LI), G2/M-phase fraction(G2/MPF) and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.Methods Fresh tumor samples from 60 patients with gastric carcinoma were analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with lymphatic vessel invasion, lymphatic node metastasis, the number of matastatic lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a fluorescent probe for total cellular DNA, and a monoclonal antibody against BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled goat anti-mouse antibody was used as a second antibody. S-phase fractions were measured by in vitro BrdUrd labeling, and DNA ploidy and G2/MPF were also measured. Comparison of survival was performed with the log-rank test, the Chi-square test for qualitative data, and Student's t test for quantu data. Results BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic vessel invasion than in those without invasion respectively (P<0.01); the patients who had tumors with lymphatic vessel invasion showed a significantly poor prognosis (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic node metastasis than in those without metastasis (P<0.01). A statistical significant difference was noted in the 5-year survival rates between the patients with lymph node metastasis and those without metastasis. Compared with diploid carcinoma, the incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P<0.05), and the patients with aneuploid carcinoma showed a significantly poor prognosis (P<0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1-4 metastatic lymph nodes (P<0

  4. Identify lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines using gene chip

    Institute of Scientific and Technical Information of China (English)

    Bo Song; Li-Hui Wang; Hua-Xin Wang; Ren-Shu Zheng; Lei Sun; Jian-Wu Tang; Bo Wang; Xiao-Nan Cui; Li Hou; Lu Sun; Li-Min Mao; Chun-Hui Zhou; Yue Du

    2005-01-01

    AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphatic metastasis potential.METHODS: Total RNA was isolated from Hca-F and Hca-P cells and synthesized into double-stranded cDNA. In vitro transcription double-stranded cDNA was labeled with biotin (i.e. biotin-labeled cRNA, used as the probe). The cRNA probes hybridized with Affymetrix GeneChip() MOE430A (containing 22 690 transcripts, including 14 500 known mouse genes and 4 371 ESTs) respectively and the signals were scanned by the GeneArray Scanner. The results were then analyzed by bioinformatics.RESULTS: Out of the 14 500 known genes investigated,110 (0.8%) were up regulated at least 23 fold. Among the total 4 371 ESTs, 17 ESTs (0.4%) (data were not presented) were up regulated at least 23 fold. According to the Gene Ontology and TreeView analysis, the 110genes were further classified into two groups: differential biological process profile and molecular function profile.CONCLUSION: Using high-throughput gene chip method,a large number of genes and their cellular functions about angiogenesis, cell adhesion, signal transduction, cell motility, transport, microtubule-based process, cytoskeleton organization and biogenesis, cell cycle, transcription,chaperone activity, motor activity, protein kinase activity,receptor binding and protein binding might be involved in the process of lymphatic metastasis and deserve to be used as potential candidates for further investigation.Cyclin D1, Fosl1, Hsp47, EGFR and AR, and Cav-1 are selected as the possible candidate genes of the metastatic phenotype, which need to be validated in later experiments.ESTs (data were not presented) might indicate novel genes associated with lymphatic metastasis. Validating the function of these genes is helpful to identify the key or candidate gene/pathway responsible for lymphatic

  5. Study Regarding the Effectiveness of Manual Lymphatic Drainage in the Case of Patients with Breast Cancer that Present Lymphedema

    OpenAIRE

    Alexandru MIOC; Corina PANTEA

    2013-01-01

    Lymphedema is defined as a persistent increase of tissue volume caused by the blocked or absent lymphatic drainage. The purpose of this study is to analyse the effectiveness of lymphatic drainage in the treatment of lymphedema after a mastectomy, with the aim of reducing the volume of the lymphedema and improving overall symptomatology, as well as providing information regarding the impact of this treatment on quality-of-life and the physical limitations of these patients. With these objectiv...

  6. Assessing progress in reducing the at-risk population after 13 years of the global programme to eliminate lymphatic filariasis.

    OpenAIRE

    Pamela J Hooper; Brian K Chu; Alexei Mikhailov; Ottesen, Eric A.; Mark Bradley

    2014-01-01

    In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000-during which over 4.4 billion treatments have been distributed in 56 endem...

  7. Lymphatic Filariasis control in Tanzania:effect of repeated mass drug administration with Ivermectin and Albendazole on infection and transmission

    OpenAIRE

    Simonsen, Paul Erik; Pedersen, Erling Møller; Rwegoshora, Rwehumbiza T.; Malecela, Mwelecele N.; Derua, Yahya A; Magesa, Stephen M

    2010-01-01

    Background In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP). Methodology/Principal Findings Infection and transmission was monitored du...

  8. Visualization of lymphatic vessels by Prox1-promoter directed GFP reporter in a bacterial artificial chromosome-based transgenic mouse

    OpenAIRE

    Choi, Inho; Chung, Hee Kyoung; Ramu, Swapnika; Lee, Ha Neul; Kim, Kyu Eui; Lee, Sunju; Yoo, Jaehyuk; Choi, Dongwon; Lee, Yong Suk; Aguilar, Berenice; Hong, Young-Kwon

    2011-01-01

    Although the blood vessel-specific fluorescent transgenic mouse has been an excellent tool to study vasculogenesis and angiogenesis, a lymphatic-specific fluorescent mouse model has not been established to date. Here we report a transgenic animal model that expresses the green fluorescent protein under the promoter of Prox1, a master control gene in lymphatic development. Generated using an approximately 200-kb-long bacterial artificial chromosome harboring the entire Prox1 gene, this Prox1-g...

  9. Mechanisms of Acute Alcohol Intoxication-Induced Modulation of Cyclic Mobilization of [Ca2+] in Rat Mesenteric Lymphatic Vessels

    Science.gov (United States)

    Kerut, Edmund K.; Breslin, Jerome W.; Molina, Patricia E.

    2015-01-01

    Abstract Background: We have demonstrated that acute alcohol intoxication (AAI) increases the magnitude of Ca2+ transients in pumping lymphatic vessels. We tested the contribution of extracellular Ca2+ via L-type Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum (SR) to the AAI-induced increase in Ca2+ transients. Methods and Results: AAI was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats; isovolumic administration of water served as the control. Mesenteric lymphatic vessels were isolated, cannulated, and loaded with Fura-2 AM to measure changes in intracellular Ca2+. Measurements were made at intraluminal pressures of 2, 6, and 10 cm H2O. L-type Ca2+ channels were blocked with nifedipine; IP-3 receptors were inhibited with xestospongin C; and SR Ca2+ release and Ca2+ pool (Ca2+ free APSS) were achieved using caffeine. Nifedipine reduced lymphatic Ca2+ transient magnitude in both AAI and control groups at all pressures tested, but reduced lymphatic contraction frequency only in the control group. Xestospongin C did not significantly change any of the Ca2+ parameters in either group; however, fractional shortening increased in the controls at low transmural pressure. RyR (ryanodine receptor) activation with caffeine resulted in a single contraction with a greater Ca2+ transient in lymphatics from AAI than those from controls. SR Ca2+ pool was also greater in lymphatics isolated from AAI- than from control animals. Conclusions: These data suggest that 1) L-type Ca2+ channels contribute to the AAI-induced increase in lymphatic Ca2+ transient, 2) blockage of IP-3 receptors could increase calcium sensitivity, and 3) AAI increases Ca2+ storage in the SR in lymphatic vessels. PMID:26056854

  10. Assessing Progress in Reducing the At-Risk Population after 13 Years of the Global Programme to Eliminate Lymphatic Filariasis

    OpenAIRE

    Pamela J Hooper; Brian K Chu; Alexei Mikhailov; Ottesen, Eric A.; Mark Bradley

    2014-01-01

    Background In 1997, the World Health Assembly adopted Resolution 50.29, committing to the elimination of lymphatic filariasis (LF) as a public health problem, subsequently targeted for 2020. The initial estimates were that 1.2 billion people were at-risk for LF infection globally. Now, 13 years after the Global Programme to Eliminate Lymphatic Filariasis (GPELF) began implementing mass drug administration (MDA) against LF in 2000—during which over 4.4 billion treatments have been distributed ...

  11. A practical strategy for responding to a case of lymphatic filariasis post-elimination in Pacific Islands

    OpenAIRE

    Harrington, Humpress; Asugeni, James; Jimuru, Christopher; Gwalaa, John; Ribeyro, Elmer; Bradbury, Richard; Joseph, Hayley; Melrose, Wayne; MacLaren, David; Speare, Rick

    2013-01-01

    Background Lymphatic filariasis (LF) due to Wuchereria bancrofti is being eliminated from Oceania under the Pacific Elimination of Lymphatic Filariasis Programme. LF was endemic in Solomon Islands but in the 2010-2020 Strategic Plan of the Global Programme to Eliminate LF, Solomon Islands was listed as non-endemic for LF. In countries now declared free of LF an important question is what monitoring strategy should be used to detect any residual foci of LF? This paper describes how a new case ...

  12. Autoradiographic investigations on the prednisolone-induced atrophy and on interdependent reactions in different lymphatic tissues of rabbit

    International Nuclear Information System (INIS)

    Under the application of 3H-thymidine the method of organ extirpation (thymectomy and appendectomy) was combined with the cell labeling technique. By autoradiographic evaluation of histologic specimens the content of labelled lymphocytes in the examined tissues was determined. Thymus, appendix, subcutaneous lymphatic nodes and spleen were examined. In the thymus the application of prednisolone induced organ atrophy. Appendectomy leads in the thymic marrow to an increase of the mitotic activity. In the appendix the application of prednisolone causes the emptying of basal lymphatic follicles. Thymectomy induces a large increase of the mitotic activity of the lymphatic tissue. Not all lymphatic nodes show identical changes after organ extirpation and after prednisolone application, but considerable differences. Only a decreased proliferation of labled lymphocytes, occuring under prednisolone application, can be detected in the marrow of the mesenteric lymphatic nodes and of the red splenic pulp in the animal with thymectomy. This result is also valid for the marrow of the remaining deep lymphatic nodes, after thymectomy and appendectomy. The lymphocyte counting in the peripheral blood done during prednisolone treatment, does not indicate that the lymphocyte values depend to a notable extent on the previous surgical treatment of the animals. (orig./MG)

  13. Stromal CEA immunoreactivity is correlated with lymphatic invasion of human esophageal carcinoma.

    Science.gov (United States)

    Kijima, H; Oshiba, G; Kenmochi, T; Kise, Y; Tanaka, H; Chino, O; Shimada, H; Ueyama, Y; Tanaka, M; Makuuchi, H

    2000-04-01

    Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e. modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human esophageal carcinomas. In this study, we examined CEA expression in human esophageal squamous cell carcinoma and its clinicopathological significance. CEA immunoreactivity was frequently detected in the cancer cells (cytoplasmic type; 81.1%, 43/53) as well as in the cancer stroma (stromal type; 32.1%, 17/53), regardless of the depth of tumor invasion. Lymphatic invasion of cancer cells was frequently found in the stromal CEA-positive esophageal cancer (44.4%, 16/36), compared to stromal CEA-negative cancer (5.9%, 1/17) (pCEA expression plays important roles in lymphatic invasion of human esophageal squamous cell carcinoma.

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

    Directory of Open Access Journals (Sweden)

    Mariana Maia Freire de Oliveira

    2015-06-01

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

  15. The emerging story of disability associated with lymphatic filariasis: a critical review.

    Directory of Open Access Journals (Sweden)

    Lynne Michelle Zeldenryk

    2011-12-01

    Full Text Available Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF, making it the second leading cause of disability in the world. Despite this, there is limited research into the experiences of people living with the disease. This review summarises the research on the experiences of people living with LF disability. The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability. Physical manifestations of LF make daily activities and participation in community life difficult. The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face.

  16. Issues in Delivering Morbidity Management for Lymphatic Filariasis Elimination: A Study in Pondicherry, South India

    Directory of Open Access Journals (Sweden)

    A. Krishna Kumari

    2012-01-01

    Full Text Available Lymphatic filariasis is a vector borne parasitic disease causing long term disability. The Global Programme to Eliminate Lymphatic Filariasis aims to achieve its objective through two strategies; Mass Drug Administration (MDA to interrupt transmission and Morbidity Management (MM to manage disability for those already affected. MDA is going on in full swing in endemic areas; but MM is lagging behind. An exploratory study was conducted in Pondicherry through focus group discussions to find out whether there are delivery issues if any, in the MM programme and get suggestions from end users. The study results show that MM has not received the same attention as MDA and there are shortcomings in the delivery mechanism of the programme. The importance of these findings are discussed and suggestions given for improving the programme.

  17. Lymphatic mapping and preoperative imaging in the management of post-mastectomy lymphoedema.

    Science.gov (United States)

    Chowdhry, Muhammed; Rozen, Warren Matthew; Griffiths, Matthew

    2016-04-01

    Early detection and diagnosis of upper extremity lymphoedema in patients after mastectomy and axillary lymph node clearance is important in order to treat disease before it is too advanced to achieve favourable outcomes. Patients with disease refractory to conservative management can be efficiently assessed for diagnosis and surgical intervention using advanced lymphatic imaging techniques. The current paper highlights the more readily available of these: lymphoscintigraphy, indocyanine green (ICG) lymphangiography and immunofluorescence, magnetic resonance lymphangiography (MRL) and computed tomographic lymphangiography in combination or individually. With such techniques, both diagnosis and treatment of lymphoedema has become more readily achieved, with lymphatico-venous and lymphatico-lymphatic anastomosis, and lymph node transfer now increasingly common undertakings. PMID:27047786

  18. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

    DEFF Research Database (Denmark)

    Dunworth, William P; Cardona-Costa, Jose; Bozkulak, Esra Cagavi;

    2014-01-01

    : Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2......RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown. OBJECTIVE...... signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox...

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

    OpenAIRE

    Mariana Maia Freire de Oliveira; Maria Teresa Pace do Amaral; Maria Salete Costa Gurgel

    2015-01-01

    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 littl...

  20. Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema

    OpenAIRE

    Avraham, Tomer; Jamie C Zampell; Yan, Alan; Elhadad, Sonia; Evan S Weitman; Stanley G Rockson; Bromberg, Jacqueline; Mehrara, Babak J.

    2013-01-01

    Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4+ T-cell inflam...

  1. Global Eradication of Lymphatic Filariasis: The Value of Chronic Disease Control in Parasite Elimination Programmes

    OpenAIRE

    Michael, Edwin; Malecela, Mwele; Zervos, Mihail; Kazura, James

    2008-01-01

    The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysi...

  2. Mass drug administration coverage evaluation survey for lymphatic Filariasis in Bagalkot and Gulbarga districts

    OpenAIRE

    Prakash Kurubarahalli Patel

    2012-01-01

    Background: Lymphatic filariasis (LF) is endemic in 83 countries and territories, with more than a billion people at risk of infection. In view with the global elimination, mass drug administration (MDA) with single dose of diethylcarbamazine and albendazole tablets was carried out for the eligible population in Bagalkot and Gulbarga districts. Objective: Assess coverage of MDA against LF in Bagalkot and Gulbarga districts. Materials and Methods: In this cross-sectional coverage evaluation su...

  3. Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis

    OpenAIRE

    Stolk, Wilma; Bosch, Quirine; De Vlas, Sake,; Fischer, Peter; Weil, Gary; Goldman, Ann

    2013-01-01

    textabstractThe Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simul...

  4. Factors determining noncompliance to mass drug administration for lymphatic filariasis elimination

    OpenAIRE

    Zinia T. Nujum; Remadevi, S; Nirmala, C.; Rajmohanan, K; Indu, PS; Nair, S. Muraleedharan

    2012-01-01

    Mass Drug Administration (MDA) for Lymphatic Filariasis (LF) elimination has been implemented worldwide and in India with a goal of eliminating the disease by 2020 and 2015 respectively. Compliance to MDA is less than adequate to achieve the goal in the desired time. This study aims to identify the factors related to awareness, acceptability and attitude and the role of certain theoretical constructs of health belief model in determining the compliant behavior to MDA. Within a cross-sectional...

  5. Morbidity management in the Global Programme to Eliminate Lymphatic Filariasis: a review of the scientific literature

    OpenAIRE

    Addiss, David G; Molly A Brady

    2007-01-01

    The Global Programme to Eliminate Lymphatic Filariasis (GPELF) has two major goals: to interrupt transmission of the parasite and to provide care for those who suffer the devastating clinical manifestations of the disease (morbidity control). This latter goal addresses three filariasis-related conditions: acute inflammatory episodes; lymphoedema; and hydrocele. Research during the last decade has confirmed the importance of bacteria as a cause of acute inflammatory episodes in filariasis-ende...

  6. Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania

    OpenAIRE

    Parker, M.; Allen, T.

    2012-01-01

    Summary This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of pe...

  7. Cessation of mass drug administration for lymphatic filariasis in zanzibar in 2006: was transmission interrupted?

    OpenAIRE

    Rebollo, MP; Mohammed, KA; Thomas, B.; Ame, S; Ali, SM; Cano, J.; Escalada, AG; Bockarie, MJ

    2015-01-01

    Author Summary Lymphatic filariasis was highly endemic in Zanzibar when MDA commenced in 2001 to eliminate the disease. In 2006, Zanzibar, in the United Republic of Tanzania, was the first territory in Africa to complete five rounds of annual treatment using a combination of albendazole and ivermectin at 100% geographic coverage and achieving effective treatment coverage of over 65% during each round. MDA was stopped in 2006 after sentinel site surveys revealed parasite infection rates of zer...

  8. ANALYSIS OF GENES ASSOCIATED WITH LYMPHATIC METASTASIS IN PANCREATIC CARCINOMA USING cDNA MICROARRAY

    Institute of Scientific and Technical Information of China (English)

    谭志军; 胡先贵; 曹贵松; 唐岩

    2003-01-01

    Objective: To identify new markers for prediction of lymph node metastasis. Methods: cDNA probes were prepared by labeling mRNA from samples of four pancreatic carcinoma tissues with Cy5-dUTP and mRNA from adjacent normal tissues with Cy3-dUTP respectively through reverse transcription. The mixed probes of each sample were then hybridized with 4,096 cDNA arrays (4,000 unique human cDNA sequences), and the fluorescent signals were scanned by ScanArray 3000 scanner (General Scanning, Inc.). The values of Cy5-dUTP and Cy3-dUTP on each spot were analyzed and calculated by ImaGene 3.0 software (BioDiscovery, Inc.). Genes that differentially expresses in each cancerous tissue were sought out according to the standard that the absolute value of natural logarithm of the ratio of Cy5 to Cy3 is greater than 0.69, i. e., more than 2 times change of gene expression, and the signal value of either Cy3 and Cy5 need to be greater than 600. Then, the genes differently expressed in cancer with and without lymphatic metastasis were screened out for further analysis. Results: Among 2 samples with lymphatic metastasis and 2 samples without metastasis, 56 genes, which accounted for 1.40% of genes on the microarray slides, exhibited differentially expression in cancerous tissues with lymphatic metastasis. There were 32 over-expressed genes including 11 having been registered in Genebank, and 24 under-expressed genes including 3 in Genebank. Conclusion: Microarray analysis may provide invaluable information to identify specific gene expression profile of lymphatic metastasis in pancreatic cancer.

  9. Lymphatic spread of mesenchymal renal tumor to metastatic parathymic lymph nodes in rat

    OpenAIRE

    Rozsa, David; Trencsenyi, Gyorgy; Kertai, Pal; Marian, Terez; Nagy, Gabor; Banfalvi, Gaspar

    2009-01-01

    Rat mesenchymal renal tumor cells (NeDe) transplanted under the kidney capsule of F344 rats resulted in metastases in the parathymic lymph nodes. Tumor cells were isolated from these tumor-bearing lymph nodes and 106 cells were implanted under the kidney capsule. Tumor growth after this implantation could be traced within six days. India ink was implanted to prove that there is a connection between the lymphatic vessels of the kidney capsule and the parathymic lymph ...

  10. Study on the mechanism of regulation on peritoneal lymphatic stomata with Chinese herbal medicine

    Institute of Scientific and Technical Information of China (English)

    Shi-Ping Ding; Ji-Cheng Li; Jian Xu; Lian-Gen Mao

    2002-01-01

    AIM: To study the mechanism of Chinese herbal medicine(CHM), the prescription consists of Radix SalviaeMiltiorrhizae , Radix Codonopsitis Pilosulae , RhizornaAtractylodis Alba and Rhizoma Alismatis, LeonurusHeterophyllus Sweet, etc ) on the regulation of theperitoneal lymphatic stomata and the ascites drainage.METHODS: The mouse model of live fibrosis wasestablished with the application of intragastric installationsof carbon tetrachloride once every three days; scanningelectron microscope and computer image processing wereused to detect the area and the distributive density of theperitoneal lymphatic stomata; and the concentrations ofurinary ion and NO in the serum were measured analyzed inthe experiment.RESULTS: Two different doses of CHM could significantlyincrease the area of the peritoneal lymphatic stomata,promote its distribution density and enhance the arainage ofurinary ion such as sodium, potassium and chlorine.Meanwhile, the NO concentration of two different doses ofCHM groups was 133.52 ± 23.57μmol/L, and 137.2 ±26.79μnol/L respectively. In comparison with the controland model groups ( 48.36 ± 6.83μmol/L, and 35.22 ±8.94μmol/L, P < 0.01 ), there existed significantly markeddifference, this made it clear that Chinese herbal medicinecould induce high endogenous NO concentration. The effectof Chinese herbal medicine on the peritoneal lymphaticstomata and the drainage of urinary ion was altered byadding NO donor (sodium nitropurruside, SNP) or NOsynthase (NOS) inhibitor (N(G)-monomethyl-L-arginine, L-NMMA) to the peritoneal cavity.CONCLUSION: There existed correlations between high NOconcentration and enlargement of the peritoneal lymphaticstomata, which result in enhanced drainage of ascites.These data supported the hypothesis that Chinese herbalmedicine could regulate the peritoneal lymphatic stomata byaccelerating the synthesis and release of endogenous NO.

  11. Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications

    OpenAIRE

    Mohammed, Rabab A. A.; Ellis, Ian O.; Elsheikh, Somaia; Paish, Emma C.; Martin, Stewart G.

    2008-01-01

    Abstract Controversy exists regarding the topography of lymph vessels in breast cancer, their usefulness as prognostic factors, relationship with angiogenesis and whether active lymphangiogenesis occurs within the tumour. A series of 177 well-characterized breast cancers, with long term follow up, were stained with D2-40, CD31 and CD34. Distribution of lymphatics and lymph vessel density (LVD) were assessed in three areas, intratumoural, peripheral and peritumoural and...

  12. A case study of risk factors for lymphatic filariasis in the Republic of Congo

    OpenAIRE

    Chesnais, Cédric B; Missamou, François; Sébastien D Pion; Bopda, Jean; Louya, Frédéric; Majewski, Andrew C.; Fischer, Peter U.; Gary J Weil; Boussinesq, Michel

    2014-01-01

    Background: Little is known regarding risk factors for lymphatic filariasis (LF) in Central Africa. We studied the epidemiology of LF in an endemic village in the Republic of Congo. Methods: Dependent variables were Wuchereria bancrofti antigenemia (ICT card test) and microfilaremia (night blood smears). The following factors were investigated: sex, age, bed net, latrines, source of water, uptake of anthelmintic drugs, hunting/fishing activities, and occasionally sleeping in the bush. Mixed m...

  13. An investigation of the disparity in estimates of microfilaraemia and antigenaemia in lymphatic filariasis surveys.

    OpenAIRE

    Cano, J; P Moraga; Nikolay, B.; Rebollo, MP; Okorie, PN; Davies, E.; Njenga, SM; Bockarie, MJ; Brooker, SJ

    2015-01-01

    BACKGROUND: The diagnosis of lymphatic filariasis (LF) is based typically on either microfilaraemia as assessed by microscopy or filarial antigenaemia using an immuno-chromatographic test. While it is known that estimates of antigenaemia are generally higher than estimates of microfilaraemia, the extent of the difference is not known. METHODS: This paper presents the results of an extensive literature search for surveys that estimated both microfilaraemia and antigenaemia in order to better u...

  14. Urban lymphatic filariasis in the metropolis of Dar es Salaam, Tanzania

    OpenAIRE

    Mwakitalu, Mbutolwe E; Malecela, Mwelecele N.; Pedersen, Erling M; Franklin W Mosha; Paul E Simonsen

    2013-01-01

    Background The last decades have seen a considerable increase in urbanization in Sub-Saharan Africa, and it is estimated that over 50% of the population will live in urban areas by 2040. Rapid growth of cities combined with limited economic resources often result in informal settlements and slums with favorable conditions for proliferation of vectors of lymphatic filariasis (LF). In Dar es Salaam, which has grown more than 30 times in population during the past 55 years (4.4 million inhabitan...

  15. A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis

    OpenAIRE

    Halliday, Alice; Guimaraes, Ana F.; Tyrer, Hayley E.; Metuge, Haelly Mejane; Patrick, Chounna Ndongmo Winston; Arnaud, Kengne-Ouafo Jonas; Kwenti, Tayong Dizzle Bita; Forsbrook, George; Steven, Andrew; Cook, Darren; Enyong, Peter; Wanji, Samuel; Taylor, Mark J; Joseph D Turner

    2014-01-01

    Background New drugs effective against adult filariae (macrofilaricides) would accelerate the elimination of lymphatic filariasis and onchocerciasis. Anti-Onchocerca drug development is hampered by the lack of a facile model. We postulated that SCID mice could be developed as a fmacrofilaricide screening model. Methods The filaricides: albendazole (ABZ), diethylcarbamazine (DEC), flubendazole (FBZ), ivermectin (IVM) and the anti-Wolbachia macrofilaricide, minocycline (MIN) were tested in Brug...

  16. Lymphatic Filariasis Transmission Risk Map of India, Based on a Geo-Environmental Risk Model

    OpenAIRE

    Sabesan, Shanmugavelu; Raju, Konuganti Hari Kishan; Subramanian, Swaminathan; Srivastava, Pradeep Kumar; Jambulingam, Purushothaman

    2013-01-01

    The strategy adopted by a global program to interrupt transmission of lymphatic filariasis (LF) is mass drug administration (MDA) using chemotherapy. India also followed this strategy by introducing MDA in the historically known endemic areas. All other areas, which remained unsurveyed, were presumed to be nonendemic and left without any intervention. Therefore, identification of LF transmission risk areas in the entire country has become essential so that they can be targeted for interventio...

  17. Cessation of Mass Drug Administration for Lymphatic Filariasis in Zanzibar in 2006: Was Transmission Interrupted?

    OpenAIRE

    Rebollo, Maria P.; Mohammed, Khalfan A.; Brent Thomas; Shaali Ame; Said Mohammed Ali; Jorge Cano; Alba Gonzalez Escalada; Bockarie, Moses J.

    2015-01-01

    Author Summary Lymphatic filariasis was highly endemic in Zanzibar when MDA commenced in 2001 to eliminate the disease. In 2006, Zanzibar, in the United Republic of Tanzania, was the first territory in Africa to complete five rounds of annual treatment using a combination of albendazole and ivermectin at 100% geographic coverage and achieving effective treatment coverage of over 65% during each round. MDA was stopped in 2006 after sentinel site surveys revealed parasite infection rates of zer...

  18. Molecular Xenomonitoring Using Mosquitoes to Map Lymphatic Filariasis after Mass Drug Administration in American Samoa

    OpenAIRE

    Mark A Schmaedick; Amanda L Koppel; Nils Pilotte; Melissa Torres; Williams, Steven A; Stephen L Dobson; Lammie, Patrick J; Won, Kimberly Y.

    2014-01-01

    Background Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed ‘molecular xenomonitoring,’ can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the ...

  19. Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

    OpenAIRE

    Bulman, Christina A.; Bidlow, Chelsea M.; Sara Lustigman; Fidelis Cho-Ngwa; David Williams; Rascón, Alberto A; Nancy Tricoche; Moses Samje; Aaron Bell; Brian Suzuki; K C Lim; Nonglak Supakorndej; Prasit Supakorndej; Wolfe, Alan R.; Knudsen, Giselle M.

    2015-01-01

    Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infe...

  20. Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection.

    OpenAIRE

    Irvine, MA; Njenga, SM; Gunawardena, S; C Njeri Wamae; Cano, J; Brooker, SJ; T Deirdre Hollingsworth

    2016-01-01

    Background Lymphatic filariasis is a debilitating neglected tropical disease that affects impoverished communities. Rapid diagnostic tests of antigenaemia are a practical alternative to parasitological tests of microfilaraemia for mapping and surveillance. However the relationship between these two methods of measuring burden has previously been difficult to interpret. Methods A statistical model of the distribution of worm burden and microfilariae (mf) and resulting antigenaemic and mf preva...

  1. The health and economic benefits of the global programme to eliminate lymphatic filariasis (2000–2014)

    OpenAIRE

    Turner, Hugo C.; Bettis, Alison A.; Brian K Chu; Deborah A McFarland; Pamela J Hooper; Ottesen, Eric A.; Mark H Bradley

    2016-01-01

    Background Lymphatic filariasis (LF), also known as elephantiasis, is a neglected tropical disease (NTD) targeted for elimination through a Global Programme to Eliminate LF (GPELF). Between 2000 and 2014, the GPELF has delivered 5.6 billion treatments to over 763 million people. Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF. Method We combined previously established models t...

  2. Evaluation of a Multivalent Vaccine against Lymphatic Filariasis in Rhesus macaque Model

    OpenAIRE

    Gajalakshmi Dakshinamoorthy; Agneta von Gegerfelt; Hanne Andersen; Mark Lewis; Ramaswamy Kalyanasundaram

    2014-01-01

    Lymphatic filariasis affects 120 million people worldwide and another 1.2 billion people are at risk of acquiring the infection. Chemotherapy with mass drug administration is substantially reducing the incidence of the infection. Nevertheless, an effective vaccine is needed to prevent the infection and eradicate the disease. Previously we reported that a multivalent fusion protein vaccine (rBmHAT) composed of small heat shock proteins 12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and l...

  3. Ongoing Surveillance for Lymphatic Filariasis in Togo: Assessment of Alternatives and Nationwide Reassessment of Transmission Status

    OpenAIRE

    Budge, Philip J.; Dorkenoo, Ameyo M.; Sodahlon, Yao K.; Fasuyi, Omofolarin B.; Mathieu, Els

    2014-01-01

    Tremendous progress has been made towards the goal of global elimination of lymphatic filariasis (LF) transmission by 2020. The number of endemic countries reducing LF transmission through mass drug administration continues to increase, and therefore, the need for effective post-intervention surveillance also continues to increase. Togo is the first sub-Saharan African country to implement LF surveillance, and it has 6 years of experience with this passive surveillance system. We herein repor...

  4. Transmission Assessment Surveys (TAS) to Define Endpoints for Lymphatic Filariasis Mass Drug Administration: A Multicenter Evaluation

    OpenAIRE

    Brian K Chu; Michael Deming; Nana-Kwadwo Biritwum; Bougma, Windtaré R.; Améyo M Dorkenoo; Maged El-Setouhy; Fischer, Peter U.; Katherine Gass; Manuel Gonzalez de Peña; Leda Mercado-Hernandez; Dominique Kyelem; Lammie, Patrick J; Rebecca M Flueckiger; Mwingira, Upendo J.; Rahmah Noordin

    2013-01-01

    BACKGROUND: Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can...

  5. Shrinking the Lymphatic Filariasis Map of Ethiopia: Reassessing the Population at Risk through Nationwide Mapping.

    OpenAIRE

    Rebollo, Maria P.; Heven Sime; Ashenafi Assefa; Jorge Cano; Kebede Deribe; Alba Gonzalez-Escalada; Oumer Shafi; Gail Davey; Brooker, Simon J.; Amha Kebede; Bockarie, Moses J.

    2015-01-01

    Author Summary About 1.4 billion people are believed to be living in areas where Lymphatic filariasis (LF) is actively transmitted. However, the distribution of this disfiguring mosquito-borne parasitic disease and the true population at risk that can be targeted for treatment have not been defined for all endemic countries. By 2013, Ethiopia had not delineated the majority of the endemic implementation units that can be targeted for MDA. Here, we present the results of a nationwide mapping e...

  6. The global distribution and transmission limits of lymphatic filariasis : past and present.

    OpenAIRE

    Cano, J; Rebollo, MP; Golding, N.; Pullan, RL; Crellen, T; Soler, A.; Kelly-Hope, LA; Lindsay, SW; Hay, SI; Bockarie, MJ; Brooker, SJ

    2014-01-01

    Background Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination by 2020 and to guide elimination efforts countries have, in recent years, conducted extensive mapping surveys. Documenting the past and present distribution of LF and its environmental limits is important for a number of reasons. Here, we present an initiative to develop a global atlas of LF and present a new global map of the limits of LF transmission. Methods We undertook a systema...

  7. Lymphatic Filariasis Control in Tanga Region, Tanzania: Status after Eight Rounds of Mass Drug Administration.

    OpenAIRE

    Paul E Simonsen; Yahya A Derua; Magesa, Stephen M; Pedersen, Erling M; Stensgaard, Anna-Sofie; Malecela, Mwelecele N.; Kisinza, William N.

    2014-01-01

    BackgroundLymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds of MDA, spot check surveys were added in the other 7 districts of Tanga Region, to assess the regional LF status.MethodsLF vector and transmission surveillance, and human cross sectional surveys in c...

  8. Hydrocele fluid: Can it be used for immunodiagnosis of lymphatic filariasis?

    OpenAIRE

    Mishra, S.; K. G. Achary; N. N. Mandal; Tripathy, A; Kar, S K; Bal, M. S.

    2014-01-01

    Background & objectives: Diagnosis of lymphatic filariasis using serum has been established but the utility of hydrocele fluid for the purpose is not exactly known. Since, hydrocele is a chronic form of the disease manifestation in a variety of situations and often poses difficulty in diagnosing its origin, we have evaluated the usefulness usage of hydrocele fluid for diagnosis of filarial origin of hydrocele in this study. Methods: Paired samples of serum and hydrocele fluid from 51 indi...

  9. Evaluation of mass drug administration in the program to control imported lymphatic filariasis in Thailand

    OpenAIRE

    Toothong, Tanaporn; Tipayamongkholgul, Mathuros; Suwannapong, Nawarat; Suvannadabba, Saravudh

    2015-01-01

    Background Migration plays a major role in the emergence and resurgence of lymphatic filariasis (LF) in many countries. Because of the high prevalence of Imported Bancroftian Filariasis (IBF) caused by nocturnally periodic Wuchereria bancrofti and the intensive movement of immigrant workers from endemic areas, Thailand has implemented two doses of 6 mg/kg diethylcarbamazine (DEC) with interval of 6 months to prevent IBF. In areas where immigrants are very mobile, the administration of DEC may...

  10. Socio-environmental variables and transmission risk of lymphatic filariasis in central and northern Mozambique

    OpenAIRE

    Isabel Manhenje; M. Teresa Galán-Puchades; Fuentes, Màrius V.

    2013-01-01

    Lymphatic filariasis (LF) is endemic in Mozambique, where it is caused by Wuchereria bancrofti with Culex quinquefasciatus as the main vector. It affects approximately 10% of the population (2 million) with about 16 million at risk. Prevalence rates in 40 out of 65 districts that together comprise the four endemic provinces Niassa, Cabo Delgado, Nampula and Zambezia were analysed with the aim of elucidating the socio-environmental variables influencing the transmission. The levels of prevalen...

  11. Lymphatic filariasis control in Tanga Region, Tanzania: status after eight rounds of mass drug administration

    OpenAIRE

    Simonsen, Paul Erik; Yahya A Derua; Magesa, Stephen M; Pedersen, Erling Møller; Stensgaard, Anna-Sofie; Malecela, Mwelecele N.; Kisinza, William N.

    2014-01-01

    BackgroundLymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds of MDA, spot check surveys were added in the other 7 districts of Tanga Region, to assess the regional LF status.MethodsLF vector and transmission surveillance, and human cross sectional surveys in c...

  12. Cocaine enhances HIV-1 gp120-induced lymphatic endothelial dysfunction in the lung

    OpenAIRE

    Zhang, Xuefeng; Jiang, Susan; Yu, Jinlong; Kuzontkoski, Paula M; Groopman, Jerome E

    2015-01-01

    Pulmonary complications are common in both AIDS patients and cocaine users. We addressed the cellular and molecular mechanisms by which HIV and cocaine may partner to induce their deleterious effects. Using primary lung lymphatic endothelial cells (L-LECs), we examined how cocaine and HIV-1 gp120, alone and together, modulate signaling and functional properties of L-LECs. We found that brief cocaine exposure activated paxillin and induced cytoskeletal rearrangement, while sustained exposure i...

  13. Conjugated Linoleic Triacylglycerols Exhibit Superior Lymphatic Absorption Than Free Conjugate Linoleic Acids and Have Antiobesity Properties.

    Science.gov (United States)

    Woo, Hyunjoon; Chung, Min-Yu; Kim, Juyeon; Kong, Daecheol; Min, Jinyoung; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2016-05-01

    This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity. PMID:27081749

  14. Surveillance and Vector Control of Lymphatic Filariasis in the Republic of Korea

    OpenAIRE

    Cho, Shin Hyeong; Ma, Da Won; Koo, Bo Ra; Shin, Hee Eun; Lee, Wook Kyo; Jeong, Byong Suk; Chu, Chaeshin; Lee, Won Ja; Cheun, Hyeng Il

    2012-01-01

    Objectives Until the early 2000s, lymphatic filariasis would commonly break out in the coastal areas in Korea. Through steady efforts combining investigation and treatment, filariasis was officially declared eradicated in 2008. This study surveyed the density of vector species of filariasis in past endemic areas, and inspected filariasis DNA from collected mosquitoes for protection against the reemergence of filariasis. Methods Between May and October 2009, mosquitoes were caught using the bl...

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

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    Xiaolong ZHAO

    2009-09-01

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

  16. The lymph lipid precursor pool is a key determinant of intestinal lymphatic drug transport.

    Science.gov (United States)

    Trevaskis, Natalie L; Porter, Christopher J H; Charman, William N

    2006-02-01

    The influence of the size and turnover kinetics of the enterocyte-based lymph lipid precursor pool (LLPP) on intestinal lymphatic drug transport has been examined. Mesenteric lymph duct-cannulated rats were infused intraduodenally with low (2-5 mg/h) or high (20 mg/h) lipid-dose formulations containing 100 microg/h halofantrine (Hf, a model drug) and 1 microCi/h (14)C-oleic acid (OA) (as a marker for lipid transport) until steady-state rates of lipid(dX(L)/dt)(ss) and drug (dD(L)/dt)(ss) transport in lymph were obtained. After 5 h, the infusion was changed to formulations of the same composition but excluding (14)C-OA and Hf, allowing calculation of the first order rate constants describing turnover of lipid (K(X)) and drug (K(D)) from the LLPP into the lymph from the washout kinetics. The mass of lipid (X(LP)) and drug (D(LP)) in the LLPP was also determined. Biliary-lipid output was determined in a separate group of rats that had been infused with the same formulations. The results indicate that after administration of high lipid doses, lymphatic drug transport is dependent on the mass of exogenous lipid available in the LLPP and the rate of lipid pool turnover into the lymph. In contrast, after administration of low lipid doses, biliary-derived endogenous lipids are most likely to be the primary drivers of drug incorporation into the LLPP and lymph. Therefore, the LLPP size and composition seem to be major determinants of lymphatic drug transport, and formulation components, which increase lipid pool size, may therefore enhance lymphatic drug transport. PMID:16249368

  17. Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation.

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    Akinori Sato

    Full Text Available Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema.

  18. Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation

    Science.gov (United States)

    Kawata, Koji; Kawada, Masaya; Jitsukawa, Sumito; Yamashita, Keiji; Sato, Noriyuki; Himi, Tetsuo; Ichimiya, Shingo

    2016-01-01

    Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs) by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema. PMID:27366905

  19. Breast Lymphatic Mapping and Sentinel Lymph Node Biopsy: State of the Art: 2015.

    Science.gov (United States)

    Reintgen, Michael; Kerivan, Lauren; Reintgen, Eric; Swaninathan, Santosh; Reintgen, Douglas

    2016-06-01

    Lymphatic mapping with sentinel lymph node biopsy (SLNB) was introduced in the 1990s as a method to stage the nodal axilla in women with breast cancer. Very quickly the technique became the standard of care because pathologic staging was more accurate and sensitive and the surgical procedure resulted in low morbidity. SLNB has continued to evolve, and the applications in breast cancer have been expanded. A review of the published data was performed to update the lymphatic mapping technique and identify key issues and trends in the application of SLNB in women with breast cancer in 2015. The importance of axillary staging continues to effect the surgical treatment of patients with breast cancer. Originally described for patients with invasive cancer, the technique now plays an important role in staging women with ductal carcinoma in situ or recurrent breast cancer and patients with advanced breast cancer who are receiving neoadjuvant chemotherapy. Histologic examinations have incorporated multiple sectioning and immunostains. The morbidity has been low, and techniques for limiting lymphedema are being introduced. Lymphatic mapping will continue to play an important role in the treatment of women with breast cancer. The SLNB will evolve by eliminating the need for radioactivity in the operating room, and the technique will become more accurate and used in expanded indications by incorporating preoperative imaging and intraoperative guidance procedures. PMID:26952594

  20. Self-Emulsifying Drug Delivery System for Enhancing Bioavailability and Lymphatic Delivery of Tacrolimus.

    Science.gov (United States)

    Cho, Hea-Young; Choi, Ji-Hoon; Oh, In-Joon; Lee, Yong-Bok

    2015-02-01

    A self-emulsifying drug delivery system (SEDDS) containing tacrolimus has been developed to enhance the bioavailability and lymphatic delivery of tacrolimus. Solubility tests, combination tests, and phase diagrams were constructed for different sorts and ratios of oils, surfactants, and cosurfactants to identify optimal formulation. Optimized SEDDS was assessed for droplet size, zeta potential, stability in various media, and in vitro release. The tacrolimus-loaded SEDDS and commercial capsule (Prograf®) were orally administered (5 mg/kg) to rats. Whole blood, and mesenteric and axillary lymph node samples were taken and the concentrations of tacrolimus were measured to evaluate pharmacokinetic characteristics and the lymphatic delivery effects. The optimized SEDDS droplets were approximately 40 nm in size and stable enough to endure gastric pH environments. The release rate of tacrolimus from SEDDS was significantly higher than that from the commercial capsule. The bioavailability of tacrolimus in SEDDS after oral administration was significantly improved versus that of Prograf®. The lymphatic targeting efficiency of the prepared SEDDS formulation showed significantly greater than that of Prograf®. Our research indicates that prepared SEDDS can be an alternative to the conventional oral formulation of tacrolimus. Furthermore, SEDDS should be explored as a potential drug carrier for other lipophilic drugs. PMID:26353739

  1. Endoscopically observable white nodule caused by distal intramural lymphatic spread of rectal cancer: a case report

    Directory of Open Access Journals (Sweden)

    Tsumura Ayako

    2012-10-01

    Full Text Available Abstract This report describes a case of rectal cancer with endoscopically observable white nodules caused by distal intramural lymphatic spread. A 57-year-old female presented to our hospital with frequent diarrhea and hemorrhoids. Computed tomography showed bilateral ovarian masses and three hepatic tumors diagnosed as rectal cancer metastases, and also showed multiple lymph node involvement. The patient was preoperatively diagnosed with stage IV rectal cancer. Colonoscopy demonstrated that primary rectal cancer existed 15 cm from the anal verge and that there were multiple white small nodules on the anal side of the primary tumor extending to the dentate line. Biopsies of the white spots were performed, and they were identified as adenocarcinoma. The patient underwent Hartmann’s procedure because of the locally advanced primary tumor. The white nodules were ultimately diagnosed as being caused by intramural lymphatic spreading because lymphatic permeation was strongly positive at the surrounding area. Small white nodules near a primary rectal cancer should be suspected of being intramural spreading. Endoscopic detection of white nodules may be useful for the diagnosis of distal intramural spread.

  2. The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review.

    Science.gov (United States)

    Atton, Giles; Gordon, Kristiana; Brice, Glen; Keeley, Vaughan; Riches, Katie; Ostergaard, Pia; Mortimer, Peter; Mansour, Sahar

    2015-12-01

    Turner syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000-1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, although is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with four-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner syndrome may be due to a failure of initial lymphatic (capillary) function.

  3. The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review.

    Science.gov (United States)

    Atton, Giles; Gordon, Kristiana; Brice, Glen; Keeley, Vaughan; Riches, Katie; Ostergaard, Pia; Mortimer, Peter; Mansour, Sahar

    2015-12-01

    Turner syndrome is a complex disorder caused by an absent or abnormal sex chromosome. It affects 1/2000-1/3000 live-born females. Congenital lymphoedema of the hands, feet and neck region (present in over 60% of patients) is a common and key diagnostic indicator, although is poorly described in the literature. The aim of this study was to analyse the medical records of a cohort of 19 Turner syndrome patients attending three specialist primary lymphoedema clinics, to elucidate the key features of the lymphatic phenotype and provide vital insights into its diagnosis, natural history and management. The majority of patients presented at birth with four-limb lymphoedema, which often resolved in early childhood, but frequently recurred in later life. The swelling was confined to the legs and hands with no facial or genital swelling. There was only one case of suspected systemic involvement (intestinal lymphangiectasia). The lymphoscintigraphy results suggest that the lymphatic phenotype of Turner syndrome may be due to a failure of initial lymphatic (capillary) function. PMID:25804399

  4. Surgical anatomy of the retroperitoneal spaces, Part III: Retroperitoneal blood vessels and lymphatics.

    Science.gov (United States)

    Mirilas, Petros; Skandalakis, John E

    2010-02-01

    In this article, we discuss the surgical anatomy of the blood vessels and the lymphatic vessels and lymph nodes found in the retroperitoneum. Retroperitoneal blood vessels include the aorta and all its branches--parietal and visceral--from the diaphragm to the pelvis, and the inferior vena cava and its tributaries. The retroperitoneal lymphatics form a very rich and extensive chain. As a general rule, lymphatics follow the arteries and named lymph nodes are found at the root of the arteries. Retroperitoneal nodes of the abdomen comprise the inferior diaphragmatic nodes and the lumbar nodes. The latter are classified as left lumbar (aortic), intermediate (interaorticovenous), and right lumbar (caval). These nodes surround the aorta and the inferior vena cava. Around the aorta lie the paraortic nodes, preaortic nodes (include celiac, superior mesenteric, inferior mesenteric nodes collecting lymph from the splanchna supplied by the homonymous arteries), and retroaortic nodes. Similarly, around the vena cava lie the paracaval, precaval, and retrocaval nodes. Pelvic nodes include the common iliac, external and internal iliac, obturator, and sacral nodes.

  5. EVALUATION OF MASS DRUG ADMINISTRATION FOR ELIMINATION OF LYMPHATIC FILARIASIS IN GUNTUR DISTRICT, ANDHRA PRADESH

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    Purnamma

    2015-02-01

    Full Text Available BACKGROUND : Lymphatic Filariasis (LF is a serious Socio Economic and Public Health problem in the world. In India, it is estimated that 554.2 million populations are at risk of Lymphatic Filariasis infection, in 243 implementation units (Districts. National Health Policy, 2002 aims at elimination of transmission and prevention of disability due to Lymphatic Filariasis (LF by the year 2015. mass drug administration (MDA against filariasis with Diethylcarbamazine (DEC combined with Albendazole (ABZto all people excluding children <2yrs, pregnant women and seriously ill persons in endemic areas once in a year. OBJECTIVE: To assess : (i The filariasis knowledge in the community, (ii To assess the coverage and compliance of MDA from the community perspective in the Guntur District. MATERIALS AND METHODS: Cross - sectional population based house to house visit. Setting : Both rural and urban areas of Guntur district outcome – Actual coverage, compliance and side effects. RESULTS: Twelve clusters, Total eligible population of 1820 were interviewed. The coverage rate was 94.6% with variation across different areas. CONCLUSION : The compliance of drug ingestion was 94.6% the side effects of DEC were minimum. The overall coverage was better in rural areas compared to urban areas.

  6. Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes.

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    Edwin Michael

    Full Text Available The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.

  7. Global eradication of lymphatic filariasis: the value of chronic disease control in parasite elimination programmes.

    Science.gov (United States)

    Michael, Edwin; Malecela, Mwele N; Zervos, Mihail; Kazura, James W

    2008-08-13

    The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, managerial impediments to executing national control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis--lymphoedema of the extremities and hydroceles--becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control lymphatic filarial disease. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at this threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for resolving this uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially.

  8. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available BACKGROUND: Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE. FINDINGS: Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number. CONCLUSIONS: Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  9. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  10. [ A comparative lympho-scintigraphic evaluation of manual lymphatic drainage and pressotherapy in edema of the arm following treatment of a breast tumor].

    Science.gov (United States)

    Janbon, C; Ferrandez, J C; Vinot, J M; Serin, D

    1990-01-01

    Manual lymphatic drainage (MLD) and pressure-therapy are part of the therapeutical gears used in physiotherapy for reducing edema. The solution to the problem of the reduction fo lymphedema of the extremities rests with the evacuation of the liquid phase and the resorption of the stagnant proteins in the interstitial compartment not being collected by the lymphatic system. The injection of a 99 Technetium-labelled colloid substance provides a functional approach to the problem of lymphatic stasis. PMID:2212876

  11. Sustained reduction in prevalence of lymphatic filariasis infection in spite of missed rounds of mass drug administration in an area under mosquito nets for malaria control

    OpenAIRE

    Shimada Masaaki; Omar Anisa A; Mukoko Dunstan A; Wamae C Njeri; Mwandawiro Charles S; Njenga Sammy M; Bockarie Moses J; Molyneux David H

    2011-01-01

    Abstract Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established by the World Health Organisation (WHO) in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem globally by 2020. Mass drug administration (MDA) of antifilarial drugs is the principal strategy recommended for global elimination. Kenya launched a National Programme for Elimination of Lymphatic Filariasis (NPELF) in Coast Region in 2002. During the same year a long...

  12. Seventh meeting of the Global Alliance to Eliminate Lymphatic Filariasis: reaching the vision by scaling up, scaling down, and reaching out

    Science.gov (United States)

    2014-01-01

    This report summarizes the 7th meeting of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF), Washington DC, November 18–19, 2012. The theme, “A Future Free of Lymphatic Filariasis: Reaching the Vision by Scaling Up, Scaling Down and Reaching Out”, emphasized new strategies and partnerships necessary to reach the 2020 goal of elimination of lymphatic filariasis (LF) as a public-health problem. PMID:24450283

  13. Seventh meeting of the Global Alliance to Eliminate Lymphatic Filariasis: reaching the vision by scaling up, scaling down, and reaching out

    OpenAIRE

    Brady, Molly

    2014-01-01

    This report summarizes the 7th meeting of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF), Washington DC, November 18–19, 2012. The theme, “A Future Free of Lymphatic Filariasis: Reaching the Vision by Scaling Up, Scaling Down and Reaching Out”, emphasized new strategies and partnerships necessary to reach the 2020 goal of elimination of lymphatic filariasis (LF) as a public-health problem.

  14. Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin

    International Nuclear Information System (INIS)

    A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m- labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99mTc-HIG compared with 99mTc-HSA, although ultimately, the blood recovery of 99mTc-HIG was significantly higher (P 99mTc-HSA. Clearance rates of radioactivity from the injection site were not sinificantly different, however, between the two agents. In patients with PMO, web space injection of 99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for normal and

  15. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

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

    Science.gov (United States)

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

    2014-03-01

    Lymphatic fistula complicating lymphedema is thought to occur due to communication between lymph vessels and the skin, which has yet to be shown objectively. The objective of this case report is to show the pathology and treatment using simultaneous lymphatic fistula resection and lymphatico-venous anastomosis (LVA). A 40-year-old woman underwent extended resection and total hip arthroplasty for primitive neuroectodermal tumor in the right proximal femur 23 years ago. Right lower limb lymphedema developed immediately after surgery and lymphatic fistula appeared in the posterior thigh. On ICG lymphography, lymph reflux toward the distal side dispersing in a fan-shape reticular pattern from the lymphatic fistula region was noted after intracutaneous injection of ICG into the foot. We performed simultaneous lymphatic fistula resection and of LVA. Pathological examination showed that the epidermis and stratum corneum of the healthy skin were lost in the lymphatic fistula region. Dilated lymph vessels were open in this region. The examinations provide the first objective evidence that the cause of lymphatic fistula may be lymph reflux from lymphatic stems to precollectors through lymphatic perforators. PMID:23908155

  17. Comparison of Three Quality of Life Instruments in Lymphatic Filariasis: DLQI, WHODAS 2.0, and LFSQQ

    Science.gov (United States)

    Thomas, Cristina; Narahari, Saravu R.; Bose, Kuthaje S.; Vivekananda, Kuthaje; Nwe, Steven; West, Dennis P.; Kwasny, Mary; Kundu, Roopal V.

    2014-01-01

    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. PMID:24587467

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    Science.gov (United States)

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  20. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    Science.gov (United States)

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the

  1. Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System.

    Science.gov (United States)

    Deckert, Martina; Brunn, Anna; Montesinos-Rongen, Manuel; Siebert, Reiner

    2016-06-01

    Primary central nervous system (CNS) lymphoma (PCNSL) is a mature lymphoma of the diffuse large B-cell lymphoma (DLBCL) type confined to the CNS. Despite cytomorphological similarities between PCNSL and systemic DLBCL, molecular differences between both entities have been identified. The exclusively topographical restriction of PCNSL to the CNS is an unexplained mystery. To address the question of whether the unique lymphatic drainage system of the CNS, which differs from that of other organs, may play a role for this peculiar behavior, we investigated a series of 20 PCNSLs for the presence of lymphatic vessels by immunohistochemistry for Lyve-1, podoplanin, and Prox-1 expression. All PCNSLs lacked lymphatic vessels and, in this regard, were similar to 20 glioblastoma multiforme samples. In contrast to these tumors, all of which were located in the deep brain parenchyma, dural and meningeal DLBCL harbored lymphatic vessels that expressed Lyve-1 (3/8 tumors), podoplanin (5/8 tumors), and Prox-1 (5/8 tumors) in areas where the tumors had invaded the fibrous tissue of the dura. These data indicate that local topographical characteristics of the specific lymphatic drainage system may contribute to confinement of the tumor cells in PCNSL and malignant gliomas. PMID:27142645

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-06-24

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

  3. Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter.

    Science.gov (United States)

    Sugaya, Makoto; Watanabe, Takahiro; Yang, Aparche; Starost, Matthew F; Kobayashi, Hisataka; Atkins, April M; Borris, Debra L; Hanan, Elisabeth A; Schimel, Daniel; Bryant, Mark A; Roberts, Nicole; Skobe, Mihaela; Staskus, Katherine A; Kaldis, Philipp; Blauvelt, Andrew

    2005-03-15

    Kaposi sarcoma-associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3+ cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors.

  4. Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

    Science.gov (United States)

    Rodgers, Jean; Bradley, Barbara; Kennedy, Peter G E; Sternberg, Jeremy M

    2015-01-01

    Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation.

  5. Increasing Coverage in Mass Drug Administration for Lymphatic Filariasis Elimination in an Urban Setting: a Study of Malindi Town, Kenya

    Science.gov (United States)

    Njomo, Doris W.; Mukoko, Dunstan A.; Nyamongo, Nipher K.; Karanja, Joan

    2014-01-01

    Introduction Implementation of Mass Drug Administration (MDA) in urban settings is an obstacle to Lymphatic Filariasis (LF) elimination. No urban-specific guidelines on MDA in urban areas exist. Malindi district urban area had received 4 MDA rounds by the time the current study was implemented. Programme data showed average treatment coverage of 28.4% (2011 MDA), far below recommended minimum of 65–80%. Methods To identify, design and test strategies for increased treatment coverage in urban areas, a quasi-experimental study was conducted in Malindi urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were purposively selected. In the pre-test phase, 947 household heads sampled using systematic random method were interviewed for quantitative data. For qualitative data, 12 Focus Group Discussions (FGDs) with single sex adult and youth male and female groups and 3 with community drug distributors (CDDs) were conducted. Forty in-depth interviews with opinion leaders and self-administered questionnaires with District Public Health officers purposively selected were carried out. The quantitative data were analyzed using SPSS version 16 and statistical significance assessed by χ2 test.The qualitative data were analyzed manually according to study's themes. Results and Discussion The identified strategies were implemented prior to and during 2012 MDA in two sub-locations (experimental) while in the third (control), usual MDA strategies were applied. In the post-test phase, 2012 MDA coverage in experimental and control sub-locations was comparatively assessed for effect of the newly designed strategies on urban MDA. Results indicated improved treatment coverage in experimental sub-locations, 77.1% in Shella and 66.0% in Barani. Central (control) sub-location also attained high coverage, 70.4% indicating average treatment coverage of 71%. Conclusion The identified strategies contributed to increased treatment coverage in experimental sites and

  6. Increasing coverage in mass drug administration for lymphatic filariasis elimination in an urban setting: a study of Malindi Town, Kenya.

    Directory of Open Access Journals (Sweden)

    Doris W Njomo

    Full Text Available INTRODUCTION: Implementation of Mass Drug Administration (MDA in urban settings is an obstacle to Lymphatic Filariasis (LF elimination. No urban-specific guidelines on MDA in urban areas exist. Malindi district urban area had received 4 MDA rounds by the time the current study was implemented. Programme data showed average treatment coverage of 28.4% (2011 MDA, far below recommended minimum of 65-80%. METHODS: To identify, design and test strategies for increased treatment coverage in urban areas, a quasi-experimental study was conducted in Malindi urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were purposively selected. In the pre-test phase, 947 household heads sampled using systematic random method were interviewed for quantitative data. For qualitative data, 12 Focus Group Discussions (FGDs with single sex adult and youth male and female groups and 3 with community drug distributors (CDDs were conducted. Forty in-depth interviews with opinion leaders and self-administered questionnaires with District Public Health officers purposively selected were carried out. The quantitative data were analyzed using SPSS version 16 and statistical significance assessed by χ(2 test.The qualitative data were analyzed manually according to study's themes. RESULTS AND DISCUSSION: The identified strategies were implemented prior to and during 2012 MDA in two sub-locations (experimental while in the third (control, usual MDA strategies were applied. In the post-test phase, 2012 MDA coverage in experimental and control sub-locations was comparatively assessed for effect of the newly designed strategies on urban MDA. Results indicated improved treatment coverage in experimental sub-locations, 77.1% in Shella and 66.0% in Barani. Central (control sub-location also attained high coverage, 70.4% indicating average treatment coverage of 71%. CONCLUSION: The identified strategies contributed to increased treatment coverage in experimental

  7. Designing urban parks that ameliorate the effects of climate change

    NARCIS (Netherlands)

    Brown, R.D.; Vanos, J.; Kenny, N.; Lenzholzer, S.

    2015-01-01

    Many inhabitants of cities throughout the world suffer from health problems and discomfort that are caused by overheating of urban areas, and there is compelling evidence that these problems will be exacerbated by global climate change. Most cities are not designed to ameliorate these effects althou

  8. Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats

    NARCIS (Netherlands)

    Sommer, Sebastian-Patrick; Sommer, Stefanie; Sinha, Bhanu; Leyh, Rainer G.

    2012-01-01

    This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum c

  9. Antibiotics can ameliorate circulatory complications of liver cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Schaffalitzky de Muckadell, Ove B

    2011-01-01

    . This review focuses on how broad spectrum antibiotics can ameliorate the haemodynamic consequences of bacterial translocation. It is possible that the use of broad spectrum antibiotics in the future may be used to prevent other complications of liver cirrhosis than spontaneous bacterial peritonitis...

  10. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Renata Mężyk-Kopeć

    Full Text Available Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC. When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i single-cell motility, (ii cell migration through a 3D Matrigel/collagen type I matrix, and (iii their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  11. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    Science.gov (United States)

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

  12. Oxazolone-induced contact hypersensitivity reduces lymphatic drainage but enhances the induction of adaptive immunity.

    Directory of Open Access Journals (Sweden)

    David Aebischer

    Full Text Available Contact hypersensitivity (CHS induced by topical application of haptens is a commonly used model to study dermal inflammatory responses in mice. Several recent studies have indicated that CHS-induced skin inflammation triggers lymphangiogenesis but may negatively impact the immune-function of lymphatic vessels, namely fluid drainage and dendritic cell (DC migration to draining lymph nodes (dLNs. On the other hand, haptens have been shown to exert immune-stimulatory activity by inducing DC maturation. In this study we investigated how the presence of pre-established CHS-induced skin inflammation affects the induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced skin inflammation we observed that lymphatic drainage was reduced and DC migration from skin to dLNs was partially compromised. At the same time, a significantly stronger adaptive immune response towards ovalbumin (OVA was induced when immunization had occurred in CHS-inflamed skin as compared to uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed skin evoked a delayed-type hypersensitivity (DTH response comparable to the one induced by conventional immunization with OVA and adjuvant in uninflamed skin. Striking phenotypic and functional differences were observed when comparing DCs from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS-inflamed skin expressed higher levels of co-stimulatory molecules and MHC molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23-p40 and more potently induced T cell activation in vitro. Immunization experiments revealed that blockade of IL-12/23-p40 during the priming phase partially reverted the CHS-induced enhancement of the adaptive immune response. Collectively, our findings indicate that CHS-induced skin inflammation generates an overall immune-stimulatory milieu, which outweighs the potentially suppressive effect of reduced lymphatic vessel function.

  13. Effects of Bothrops asper snake venom on lymphatic vessels: insights into a hidden aspect of envenomation.

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    Javier Mora

    Full Text Available BACKGROUND: Envenomations by the snake Bothrops asper represent a serious medical problem in Central America and parts of South America. These envenomations concur with drastic local tissue pathology, including a prominent edema. Since lymph flow plays a role in the maintenance of tissue fluid balance, the effect of B. asper venom on collecting lymphatic vessels was studied. METHODOLOGY/PRINCIPAL FINDINGS: B. asper venom was applied to mouse mesentery, and the effects were studied using an intravital microscopy methodology coupled with an image analysis program. B. asper venom induced a dose-dependent contraction of collecting lymphatic vessels, resulting in a reduction of their lumen and in a halting of lymph flow. The effect was reproduced by a myotoxic phospholipase A(2 (PLA(2 homologue isolated from this venom, but not by a hemorrhagic metalloproteinase or a coagulant thrombin-like serine proteinase. In agreement with this, treatment of the venom with fucoidan, a myotoxin inhibitor, abrogated the effect, whereas no inhibition was observed after incubation with the peptidomimetic metalloproteinase inhibitor Batimastat. Moreover, fucoidan significantly reduced venom-induced footpad edema. The myotoxic PLA(2 homologue, known to induce skeletal muscle necrosis, was able to induce cytotoxicity in smooth muscle cells in culture and to promote an increment in the permeability to propidium iodide in these cells. CONCLUSIONS/SIGNIFICANCE: Our observations indicate that B. asper venom affects collecting lymphatic vessels through the action of myotoxic PLA(2s on the smooth muscle of these vessels, inducing cell contraction and irreversible cell damage. This activity may play an important role in the pathogenesis of the pronounced local edema characteristic of viperid snakebite envenomation, as well as in the systemic biodistribution of the venom, thus representing a potential therapeutical target in these envenomations.

  14. Manual lymphatic drainage and therapeutic ultrasound in liposuction and lipoabdominoplasty post-operative period

    Directory of Open Access Journals (Sweden)

    Igor F. B. Masson

    2014-01-01

    Full Text Available Background: Physiotherapy in the plastic surgery post-operative (PO is essential to provide means for an adequate and fast recovery as it restores function through the use of physiotherapeutic procedures. Aim: The aim of the following study is to verify the effects of the association between the manual lymphatic drainage and the therapeutic ultrasound on pain, oedema and the tissue fibrosis in liposuction and lipoabdominoplasty PO. Design: This is a clinical trial prospective. Materials and Methods: Eighteen women aged between 18 and 60 years participated in this study, in the late PO period following lipoabdominoplasty or liposuction in the abdomen, flanks and lower trunk, which showed tissue fibrosis of the flanks and abdomen regions. They were divided into two groups: Liposuction group and lipoabdominoplasty group. A total of twelve sessions of therapeutic ultrasound followed by the manual lymphatic drainage were performed. The patients were assessed with regard to pain, oedema and tissue fibrosis in different moments: Initial assessment, during assessment and final assessment through the application of the protocol of evaluation of cysts fibrosis levels. Statistical Analysis: The test of equality for two proportions and the confidence interval test for mean to evaluate the distribution of variables. The significance level adopted for statistical tests was 5% (P < 0.05. Results: There was a statistically significant reduction of pain, swelling and tissue fibrosis in both groups. Conclusion: the association between manual lymphatic drainage and the therapeutic ultrasound reduced the swelling and the tissue fibrosis and made pain disappear in liposuction and lipoabdominoplasty PO period.

  15. Differential lectin binding on walls of thoraco-cervical blood vessels and lymphatics in rats.

    Science.gov (United States)

    Kagami, H; Uryu, K; Okamoto, K; Sakai, H; Kaneda, T; Sakanaka, M

    1991-08-01

    Lectin binding in the walls of large to medium-sized blood vessels and lymphatics in the rat thoraco-cervical region was examined histochemically. The tunica intima of the aorta and superficial cervical artery showed positive reactions with wheat germ agglutinin (WGA) and Concanavalin A (ConA) but not with Dolichus biflorus agglutinin (DBA). The tunica media of the aorta exhibited intense WGA binding, especially on the smooth muscle cells, but the tunica media of the superficial cervical artery did not react with the lectin. Neither ConA nor DBA bound to the tunica media of the aorta and superficial cervical artery. The tunica adventitia of both arteries contained sites binding the three lectins, although DBA reactivity declined as the vascular diameter decreased. The tunica intima of the superior vena cava and azygos vein exhibited positive WGA and ConA binding, whereas DBA binding was noted on only part of the tunica intima of the superior vena cava and not on that of the azygos vein. The tunica media and tunica adventitia were reactive for all three lectins. The WGA and ConA binding sites in the tunica adventitia showed loose networks, suggesting lectin binding on connective tissue elements interlacing among smooth muscle bundles. Lectin binding sites in the walls of lymphatics exhibited an arrangement similar to those in the walls of the veins. Moreover valves protruding into the lumen showed intense WGA and ConA binding and scattered DBA binding. Three other lectins (Ulex europaeus agglutinin, peanut agglutinin, Maclura pomifera) were examined, but they showed no reactions with the vessels. Thus, the differential binding of lectins on the walls of blood vessels and lymphatics of various sizes suggests the functional complexity of monosaccharide residues in the vascular walls. PMID:1758681

  16. Inhibition of lymphatic metastases by a survivin dominant-negative mutant.

    Science.gov (United States)

    Xu, Guang-Chao; Zhang, Peng; Leng, Fei; Pan, Li; Li, Zhi-Yong; Yu, Dan-Dan; Shan, Yan; Yuan, Qing-Zhong; Wen, Yuan; Mu, Bo; Shi, Hua-Shan; Chen, Xiang; Wang, Chun-Ting

    2012-01-01

    Metastasis is the most lethal attribute of human malignancy. High-level expression of survivin is involved in both carcinogenesis and angiogenesis in cancer. Previous studies indicate that a mutation of the threonine residue at position 34 (Thr34Ala) of survivin generates a dominant-negative mutant that induces apoptosis, inhibits angiogenesis, and suppresses highly metastatic breast carcinoma in mouse models. We investigated the efficacy of gene therapy with a survivin dominant-negative mutant and possible factors related to lymph node metastasis. The metastasis rate was compared between each group in order to find a survivin-targeted therapy against lymphangiogenesis in its earliest stages. We established lymph node metastasis models and treated animals with H22 tumors with Lip-mSurvivinT34A (Lip-mS), Lip-plasmid (Lip-P), or normal saline (NS). Eight days after the last dose, five randomly chosen mice from each group were sacrificed. We detected the apoptotic index, microvessel density (MVD), lymphatic microvessel density (LMVD), and the expression of VEGF-D with immunohistochemistry. After the remaining animals were sacrificed, we compared the tumor-infiltrated lymph nodes in each group. Administration of mSurvivinT34A plasmid complexed with cationic liposome (DOTAP/chol) resulted in the efficacious inhibition of tumor growth and lymph node metastasis within the mouse H22 tumor model. These responses were associated with tumor cell apoptosis, and angiogenesis and lymphangiogenesis inhibition. Our results suggested that Lip-mSurvivinT34A induced apoptosis and inhibited tumor angiogenesis and lymphangiogenesis, thus suppressing tumor growth and lymphatic metastasis. The mSurvivinT34A survivin mutant is a promising strategy of gene therapy to inhibit lymphatic metastasis. PMID:24139416

  17. Effect of intestinal lymphatic circulation blockage in two-hit rats

    Institute of Scientific and Technical Information of China (English)

    Chun-Yu Niu; Ji-Cheng Li; Zi-Gang Zhao; Jing Zhang; Xue-Hui Shao

    2006-01-01

    AIM: To study the effect of blocking intestinal lymphatic circulation in two-hit rats and explore the significance of intestinal lymphatic circulation in two-hit.METHODS: Wistar rats were divided equally into three groups: mesenteric lymph duct ligation group, nonligation group and sham group. Mesenteric lymph was diverted by ligation of mesenteric lymph duct, and the two-hit model was established by hemorrhage and lipopolysaccharide (LPS) methods. All rats were sampled for serum pre-experiment and 24 h postexperiment. The organs including kidney, liver, lung and heart were collected for pathomorphologic observation and biochemical investigation. The nitric oxide (NO),malondialdehyde (MDA) and superoxide dismutase (SOD)were determined in serum and tissue homogenate.RESULTS: Pathomorphology study showed that the structures of kidney, lung, liver and heart tissues were normal in sham group; congestion, degeneration and necrosis in non-ligation group; but only mild lesions in ligation group. After two-hits, the contents of AST, ALT,BUN, Cr and LDH-1 in the serum of non-ligation group and ligation group were obviously higher than that in pre-experiment group and sham group, but obviously lower than that in non-ligation group. The contents of NO2-/NO3-, NOS, iNOS and MDA in the serum of nonligation group were significantly increased, compared with pre-experiment and sham group, but SOD was significantly lower. These parameters were significantly different in ligation group compared with that in sham group, but NO2-/NO3-, iNOS and MDA in ligation group were significantly lower than that in non-ligation group.CONCLUSION: Ligation of mesenteric lymph duct could improve the disturbance of organic function and morphologic damage in two-hit rats; the lymphatic mechanism in two-hit should be emphasized.

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

    Directory of Open Access Journals (Sweden)

    Aula Ammar

    2011-01-01

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

  19. Challenges in mass drug administration for treating lymphatic filariasis in Papua, Indonesia

    OpenAIRE

    Bhullar Navneet; Maikere Jacob

    2010-01-01

    Abstract Background The World Health Organization (WHO) Global Program to Eliminate Lymphatic Filariasis relies on mass drug administration (MDA) of two drugs annually for 4 to 6 years. The goal is to reduce the reservoir of microfilariae in the blood to a level insufficient to maintain transmission by the mosquito vector. In 2008, the international medical aid organization Médecins Sans Frontières (MSF) performed the first round of a MDA in the high-burden area of Asmat district, in Papua, I...

  20. Assessing numbers and faces: a prerequisite for improving access to lymphatic filariasis morbidity care.

    Science.gov (United States)

    Becker, Sören L; Fürst, Thomas; Addiss, David G; Utzinger, Jürg

    2015-06-01

    Concerted efforts to eliminate lymphatic filariasis worldwide have registered success; multiple rounds of mass drug administration have led to the interruption of transmission in many previously endemic areas. However, the management of patients with established clinical disease (e.g., lymphoedema, hydrocoele and acute dermatolymphangioadenitis) has not been addressed sufficiently. Two recent studies from Malawi underscore the need for accurate epidemiological and clinical data, and comprehensive morbidity assessments across various domains of daily life. Addressing these issues will guide the implementation of programmes to improve access to treatment and disability prevention for affected individuals in Malawi and beyond.

  1. Mast cells in common wolffish Anarhichas lupus L.: ontogeny, distribution and association with lymphatic vessels.

    Science.gov (United States)

    Hellberg, Hege; Bjerkås, Inge; Vågnes, Øyvind B; Noga, Edward J

    2013-12-01

    The morphology, ontogeny and tissue distribution of mast cells were studied in common wolffish(Anarhichas lupus L.) at the larval, juvenile and adult life stages using light and electron-microscopy and immunohistochemistry. Fish were sampled at 1 day, 1, 2, 3, 4, 8 and 12 weeks post-hatching in addition to 6 and 9 months and 2 years and older. From 8 weeks post-hatching, mast cells in common wolffish mainly appeared as oval or rounded cells 8-15 mm in diameter with an eccentrically placed, ovoid nucleus and filled with cytoplasmic granules up to 1.2 mm in diameter. Granules were refractile and eosinophilic to slightly basophilic in H&E and stained bright red with Martius-scarlet-blue and purple with pinacyanol erythrosinate in formalin-fixed tissues. Mast cells stained positive for piscidin 4 and Fc ε RI by immunohistochemistry. From 1 day to 4 weeks post-hatching, immature mast cell containing only a few irregularly sized cytoplasmic granules were observed by light and electron-microscopy in loose connective tissue of cranial areas. From 1 day post-hatching, these cells stained positive for piscidin 4 and Fc ε RI by immunohistochemistry. From 12 weeks post-hatching, mast cells showed a primarily perivascular distribution and were particularly closely associated with lymphatic vessels and sinuses. Mast cells were mainly located at the peripheral border of the adventitia of arteries and veins, while they were in intimate contact with the endothelium of the lymphatic vessels. Numerous mast cells were observed in the intestine. A stratum compactum, as described in salmonids, was not observed in wolffish intestine,nor were mast cells confined to a separate layer, a stratum granulosum. Lymphatic vessels consisting of endothelium, intimal connective tissue and a poorly developed basal lamina were observed in the intestine. Scanning electron microscopy was used to compare the structure and localization of intestinal mast cells of common wolffish and rainbow trout

  2. Subcutaneously Administered Ultrafine PLGA Nanoparticles Containing Doxycycline Hydrochloride Target Lymphatic Filarial Parasites.

    Science.gov (United States)

    Singh, Yuvraj; Srinivas, Adepu; Gangwar, Mamta; Meher, Jaya Gopal; Misra-Bhattacharya, Shailja; Chourasia, Manish K

    2016-06-01

    Systemic chemotherapeutic targeting of filarial parasites is unfocused due to their deep seated location in lymphatic vessels. This warrants a prolonged dosing regimen in high doses for an anthelmintic like doxycycline hydrochloride (DOX). In order to provide an alternative, we have constructed ultrafine PLGA nanoparticles of DOX (DPNPs), so as to exploit the peculiarity of lymphatic vasculature underneath the subcutaneous layer of skin, which preferentially allows entry of only 10-100 nm sized particles. DPNPs were constructed using a novel solvent diffusion method aided by probe sonication, which resulted in an average size 95.43 ± 0.8 nm as per DLS, PDI 0.168 ± 0.03, zeta potential -7.38 ± 0.32, entrapment efficiency 75.58 ± 1.94%, and refrigerator stability of 7 days with respect to size in the optimized batch. TEM further substantiated the spherical shape of DPNPs along with their actual nonhydrated size as being well below 100 nm. FTIR analysis of DOX, dummy nanoparticles, and freeze-dried DPNPs revealed that the formulation step did not induce prominent changes in the chemical nature of DOX. The drug release was significantly altered (p < 0.05) with 64.6 ± 1.67% release in 48 h from DPNPs and was dictated by Fickian diffusion. Pharmacokinetic studies in Wistar rats further revealed that DPNPs caused a 16-fold prolongation in attainment of plasma Tmax and a 2-fold extension of elimination half-life (28.569 ± 1.27 h) at a dose of 5 mg/kg when compared to native drug (DOX solution) of the same strength. Contrastingly the trend was reversed in regional lymph nodes where Cmax for DPNPs (820 ± 84 ng/mg) was 4-fold greater, and lymphatic Tmax was attained in one-fourth of what was required for DOX solution. This size based preferential lymphatic targeting resulted in significantly greater in vivo antifilarial activity of DPNPs when compared to DOX solution as gauged by several parameters in Brugia malayi infected Mastomys coucha. Interestingly, the

  3. Seroprevalence and Spatial Epidemiology of Lymphatic Filariasis in American Samoa after Successful Mass Drug Administration

    OpenAIRE

    Lau, Colleen L.; Won, Kimberly Y.; Luke Becker; Soares Magalhaes, Ricardo J.; Saipale Fuimaono; Wayne Melrose; Lammie, Patrick J; Graves, Patricia M

    2014-01-01

    Background As part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000–2006, and passed transmission assessment surveys in 2011–2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk. Methods ELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected i...

  4. Assessing numbers and faces: a prerequisite for improving access to lymphatic filariasis morbidity care.

    Science.gov (United States)

    Becker, Sören L; Fürst, Thomas; Addiss, David G; Utzinger, Jürg

    2015-06-01

    Concerted efforts to eliminate lymphatic filariasis worldwide have registered success; multiple rounds of mass drug administration have led to the interruption of transmission in many previously endemic areas. However, the management of patients with established clinical disease (e.g., lymphoedema, hydrocoele and acute dermatolymphangioadenitis) has not been addressed sufficiently. Two recent studies from Malawi underscore the need for accurate epidemiological and clinical data, and comprehensive morbidity assessments across various domains of daily life. Addressing these issues will guide the implementation of programmes to improve access to treatment and disability prevention for affected individuals in Malawi and beyond. PMID:25778735

  5. Study on the risk factors of lymphatic metastasis and the indications of less invasive operations in early gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Bo Jian Jiang; Rong Xun Sun; Hao Lin; You Fu Gao

    2000-01-01

    The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic accuracy of early gastric cancer (EGC) without lymphatic metastasis has obviously improved with an improvement in the diagnostic technique and due to the accumulation of knowledge on the biological profiles of EG C[10-17]. The D2 lymph node excision was used as a regular operation to treat the EGC previously. But the concept for the EGC without lymphatic metastasis has gradually changed and the less invasive resections has been applied in some cases[18-20]. This study aimed at investigating the risk factors of lymphatic metastasis in EGC in order to find out the proofs for the suitable indications for less invasive operations such as endoscopic mucosal resectioning (EMR), laparoscopic and laparotomic resectioning.

  6. Dietary Consumption of Virgin Coconut Oil Ameliorates Lipid Profiles in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    A. M. Akinnuga

    2014-01-01

    Full Text Available Virgin coconut oil (VCO is a saturated fat with promising antidiabetic properties but its ameliorative effect on lipid profiles in diabetics is rarely reported. Therefore, in this study, a total of fifteen (15 male rats weighing 200–250 g were divided into 3 experimental groups (n=5. Group I (control and Group II (diabetic control group were fed a normal rat chow while Group III (diabetic test group was fed a 10% VCO diet for 3 weeks. Group II and Group III were made diabetic by intraperitoneal injection of 150 mg/kg of alloxan. After 72 hours of injection, blood glucose was tested to confirm diabetes mellitus. After 3 weeks, the animals were sacrificed to collect blood samples for lipid profile analysis. The results showed a significant increase in concentrations of triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein and decrease in concentration of high density lipoprotein in Group II when compared to Group I. Also, the concentrations of triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein except high density lipoprotein significantly reduced in Group III when compared to Group II (P<0.01, 0.001. VCO consumption can be claimed to ameliorate lipid levels in diabetes mellitus.

  7. Correlation between theoretical anatomical patterns of lymphatic drainage and lymphoscintigraphy findings during sentinel node detection in head and neck melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, Monica; Ruiz, Diana Milena [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Vidal-Sicart, Sergi; Paredes, Pilar; Pons, Francesca [Hospital Clinic de Barcelona, Nuclear Medicine Department, Barcelona (Spain); Institut d' Investigacions Biomediques Agusti Pi i Sunyer (IDIBAPS), Barcelona (Spain); Torres, Ferran [Hospital Clinic Barcelona, Statistical of Biostatistics and Data Management Core Facility, IDIBAPS, Barcelona (Spain); Universitat Autonoma de Barcelona, Biostatistics Unit, Faculty of Medicine, Barcelona (Spain)

    2016-04-15

    In the diagnosis of head and neck melanoma, lymphatic drainage is complex and highly variable. As regional lymph node metastasis is one of the most important prognostic factors, lymphoscintigraphy can help map individual drainage patterns. The aim of this study was to compare the results of lymphoscintigraphy and sentinel lymph node (SLN) detection with theoretical anatomical patterns of lymphatic drainage based on the location of the primary tumour lesion in patients with head and neck melanoma. We also determined the percentage of discrepancies between our lymphoscintigraphy and the theoretical location of nodal drainage predicted by a large lymphoscintigraphic database, in order to explain recurrence and false-negative SLN biopsies. In this retrospective study of 152 patients with head and neck melanoma, the locations of the SLNs on lymphoscintigraphy and detected intraoperatively were compared with the lymphatic drainage predicted by on-line software based on a large melanoma database. All patients showed lymphatic drainage and in all patients at least one SLN was identified by lymphoscintigraphy. Of the 152 patients, 4 had a primary lesion in areas that were not described in the Sydney Melanoma Unit database, so agreement could only be evaluated in 148 patients. Agreement between lymphoscintigraphic findings and the theoretical lymphatic drainage predicted by the software was completely concordant in 119 of the 148 patients (80.4 %, 95 % CI 73.3 - 86 %). However, this concordance was partial (some concordant nodes and others not) in 18 patients (12.2 %, 95 % CI 7.8 - 18.4 %). Discordance was complete in 11 patients (7.4 %, 95 % CI 4.2 - 12.8 %). In melanoma of the head and neck there is a high correlation between lymphatic drainage found by lymphoscintigraphy and the predicted drainage pattern and basins provided by a large reference database. Due to unpredictable drainage, preoperative lymphoscintigraphy is essential to accurately detect the SLNs in head and

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

  9. Lymphoscintigraphy for sentinel lymph node mapping in Japanese patients with malignant skin neoplasms of the lower extremities. Comparison with previously investigated Japanese lymphatic anatomy

    International Nuclear Information System (INIS)

    Lymph nodes (LN) and lymphatic drainage were identified by lymphoscintigraphy using 99mTc-phytate in order to map the sentinel lymph nodes (SLNs) in patients with malignant skin neoplasms of the lower extremities, and to compare the results with an atlas of Japanese lymphatic anatomy. Sentinel lymphoscintigraphs of 18 patients with malignant skin neoplasms of the lower extremities (9 men, 9 women; age range 45-84 years, mean age 66 years) were analyzed retrospectively, and the LNs detected were identified as SLNs or secondary nodes. The patterns of lymphatic drainage were divided into three different categories: initial drainage into inguinal LN without visualization of popliteal LNs (inguinal type), initial drainage into popliteal LNs and then into intrapelvic LNs (popliteal type), and initial drainage into both popliteal and inguinal LNs (inguinal and popliteal type). More than half of the cases were the inguinal and popliteal type, as both inguinal and popliteal LNs were identified as SLNs. In the cases in which the hallux and its surrounding area were injected, all were the inguinal type and popliteal LNs were not visualized. In one case, only dynamic images detected lymphatic drainage without visualization of popliteal LNs. In contrast to the previously published literature on Japanese lymphatic anatomy, SLN lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However, in agreement with currently accepted anatomy, only the great saphenous lymphatic vessel drained the skin of the hallux and its surrounding area. The present results suggest that it is important to confirm lymphatic drainage in order to identify SLNs in the lower extremities. The patterns of lymphatic drainage from the skin of the foot were divided into three different categories. In contrast to previously published Japanese lymphatic anatomy, lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However

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

    Directory of Open Access Journals (Sweden)

    Li Jie

    2010-02-01

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

  11. Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania

    DEFF Research Database (Denmark)

    Kisoka, William J.; Simonsen, Paul Erik; Malecela, Mwelecele N.;

    2014-01-01

    BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interrupt......BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission...

  12. 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

    campaign implemented in 2011 by the National Lymphatic Filariasis Elimination Programme. The study revealed a wide variation of perceptions and experiences regarding the aim, rationale and justification of MDA. There were positive sentiments about the usefulness of the drugs, but many study participants...... were sceptical about the manner in which MDA is implemented. People were particularly disappointed with the limited attempts by implementers to share information and mobilize residents. In addition, negative sentiments towards MDA for lymphatic filariasis reflected a general feeling of desertion...

  13. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Müllertz, Anette;

    2002-01-01

    triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration...... animals, and this was most pronounced for the animals dosed with the structured triglycerides. CONCLUSIONS: Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption...... in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil....

  14. Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

    Directory of Open Access Journals (Sweden)

    Oh KS

    2014-06-01

    Full Text Available Keun Sang Oh,1 Ji Young Yhee,2 Dong-Eun Lee,3 Kwangmeyung Kim,2 Ick Chan Kwon,2 Jae Hong Seo,4 Sang Yoon Kim,5 Soon Hong Yuk1,4 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul, 3Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, 4Biomedical Research Center, Korea University Guro Hospital, Seoul, 5Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea Abstract: Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma™ (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results

  15. Lymphatic filariasis in Peninsular Malaysia: a cross-sectional survey of the knowledge, attitudes, and practices of residents

    OpenAIRE

    Al-Abd, Nazeh M; Nor, Zurainee Mohamed; Ahmed, Abdulhamid; Al-Adhroey, Abdulelah H.; Mansor, Marzida; Kassim, Mustafa

    2014-01-01

    Background Lymphatic filariasis (LF) is a major cause of permanent disability in many tropical and sub-tropical countries of the world. Malaysia is one of the countries in which LF is an endemic disease. Five rounds of the mass drug administration (MDA) program have been conducted in Malaysia as part of the Global Program to Eliminate Lymphatic Filariasis (GPELF) by year 2020. This study investigated the level of awareness of LF and the MDA program in a population living in an endemic area of...

  16. Taking the lymphatic system into consideration in nursing : How lymphedema impacts the breast cancer patients’ quality of life

    OpenAIRE

    Haapiainen, Tiina

    2015-01-01

    The lymphatic system has several vital functions to maintain a healthy immune system. Breast cancer-related lymphedema is a non-curable condition that refers to post-surgical chronic and painful swelling of the upper limb. The aim of this study was to review existing literature to see what information is available for nurses about the importance of the lymphatic system. The study focused on breast cancer related lymphedema patients and two research questions were asked 1) What are some of the...

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

    Directory of Open Access Journals (Sweden)

    R Anuradha

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

  18. Comparison of Methods for Xenomonitoring in Vectors of Lymphatic Filariasis in Northeastern Tanzania.

    Science.gov (United States)

    Irish, Seth R; Stevens, William M B; Derua, Yahya A; Walker, Thomas; Cameron, Mary M

    2015-11-01

    Monitoring Wuchereria bancrofti infection in mosquitoes (xenomonitoring) can play an important role in determining when lymphatic filariasis has been eliminated, or in focusing control efforts. As mosquito infection rates can be low, a method for collecting large numbers of mosquitoes is necessary. Gravid traps collected large numbers of Culex quinquefasciatus in Tanzania, and a collection method that targets mosquitoes that have already fed could result in increased sensitivity in detecting W. bancrofti-infected mosquitoes. The aim of this experiment was to test this hypothesis by comparing U.S. Centers for Disease Control and Prevention (CDC) light traps with CDC gravid traps in northeastern Tanzania, where Cx. quinquefasciatus is a vector of lymphatic filariasis. After an initial study where small numbers of mosquitoes were collected, a second study collected 16,316 Cx. quinquefasciatus in 60 gravid trap-nights and 240 light trap-nights. Mosquitoes were pooled and tested for presence of W. bancrofti DNA. Light and gravid traps collected similar numbers of mosquitoes per trap-night, but the physiological status of the mosquitoes was different. The estimated infection rate in mosquitoes collected in light traps was considerably higher than in mosquitoes collected in gravid traps, so light traps can be a useful tool for xenomonitoring work in Tanzania. PMID:26350454

  19. In search of a potential diagnostic tool for molecular characterization of lymphatic filariasis.

    Science.gov (United States)

    Saeed, Mohd; Adnan, Mohd; Khan, Saif; Al-Shammari, Eyad; Mustafa, Huma

    2016-01-01

    Lymphatic filariasis (LF) is a chronic disease and is caused by the parasites Wuchereria bancrofti (W. bancrofti), Brugia malayi (B. malayi) and Brugia timori (B. timori). In the present study, Setaria cervi (S. cervi), a bovine filarial parasite has been used. Previously, it has been reported that the S. cervi shares some common proteins and antigenic determinants with that of human filarial parasite. The larval stages of filarial species usually cannot be identified by classical morphology. Hence, molecular characterization allows the identification of the parasites throughout all their developmental stages. The genomic DNA of S. cervi adult were isolated and estimated spectrophotometrically for the quantitative presence of DNA content. Screening of DNA sequences from filarial DNA GenBank and Expressed Sequence Tags (EST's) were performed for homologous sequences and then multiple sequence alignment was executed. The conserved sequences from multiple sequence alignment were used for In Silico primer designing. The successfully designed primers were used further in PCR amplifications. Therefore, in search of a promising diagnostic tool few genes were identified to be conserved in the human and bovine filariasis and these novel primers deigned may help to develop a promising diagnostic tool for identification of lymphatic filariasis. PMID:26751881

  20. Comparison of Methods for Xenomonitoring in Vectors of Lymphatic Filariasis in Northeastern Tanzania.

    Science.gov (United States)

    Irish, Seth R; Stevens, William M B; Derua, Yahya A; Walker, Thomas; Cameron, Mary M

    2015-11-01

    Monitoring Wuchereria bancrofti infection in mosquitoes (xenomonitoring) can play an important role in determining when lymphatic filariasis has been eliminated, or in focusing control efforts. As mosquito infection rates can be low, a method for collecting large numbers of mosquitoes is necessary. Gravid traps collected large numbers of Culex quinquefasciatus in Tanzania, and a collection method that targets mosquitoes that have already fed could result in increased sensitivity in detecting W. bancrofti-infected mosquitoes. The aim of this experiment was to test this hypothesis by comparing U.S. Centers for Disease Control and Prevention (CDC) light traps with CDC gravid traps in northeastern Tanzania, where Cx. quinquefasciatus is a vector of lymphatic filariasis. After an initial study where small numbers of mosquitoes were collected, a second study collected 16,316 Cx. quinquefasciatus in 60 gravid trap-nights and 240 light trap-nights. Mosquitoes were pooled and tested for presence of W. bancrofti DNA. Light and gravid traps collected similar numbers of mosquitoes per trap-night, but the physiological status of the mosquitoes was different. The estimated infection rate in mosquitoes collected in light traps was considerably higher than in mosquitoes collected in gravid traps, so light traps can be a useful tool for xenomonitoring work in Tanzania.

  1. An ELISA kit with two detection modes for the diagnosis of lymphatic filariasis.

    Science.gov (United States)

    Wongkamchai, S; Satimai, W; Loymek, S; Nochot, H; Boitano, J J

    2015-09-01

    The aim of this study was to develop a low-cost antifilarial immunoglobulin (Ig) G4 detection kit for the diagnosis of lymphatic filariasis. The kit was designed to be used by minimally trained personnel without the constraints of expensive laboratory equipment. We provide a description of the development and validation of a single-serum-dilution based enzyme-linked immunosorbent assay (ELISA) kit with ready-to-use reagents for measuring antifilarial IgG4 antibodies. The kit was tested on residents in Brugia malayi-endemic areas in southern Thailand. Detection was performed by naked-eye observation of the resultant colour of the immunological reactivity. The coefficient of variation (CV) was used to assess the reproducibility of the results. Long-term stability was measured over a 6-month period. Sensitivity of the test kit was 97% when compared with microfilariae detection in thick blood smears. Specificity was 98.7% based on the sera of 57 patients living outside the endemic areas who were infected with other parasites and 100 parasite-free subjects. All positive CVs were filariasis-endemic areas and compared with outcome colours of the test samples by the naked eye. Subsequent ELISA evaluation of these results using an ELISA reader indicated high agreement by the kappa statistic. These results demonstrate that the test kit is efficient and useful for public health laboratories as an alternative tool for the diagnosis of lymphatic filarial infection.

  2. Preparation and Evaluation of Solid-Self-Emulsifying Drug Delivery System Containing Paclitaxel for Lymphatic Delivery

    Directory of Open Access Journals (Sweden)

    Hea-Young Cho

    2016-01-01

    Full Text Available Solid-self-emulsifying drug delivery system (S-SEDDS of paclitaxel (Ptx was developed by the spray drying method with the purpose of improving the low bioavailability (BA of Ptx. 10% oil (ethyl oleate, 80% surfactant mixture (Tween 80 : Carbitol, 90 : 10, w/w, and 10% cosolvent (PEG 400 were chosen according to their solubilizing capacity. The mean droplet size, zeta potential, and encapsulation efficiency of the prepared S-SEDDS were 16.9 ± 1.53 nm, 12.5 ± 1.66 mV, and 56.2 ± 8.1%, respectively. In the S-SEDDS, Ptx presents in the form of molecular dispersion in the emulsions or is distributed in an amorphous state or crystalline with very small size. The prepared S-SEDDS formulation showed 70 and 75% dissolution in 60 and 30 min in dissolution medium pH 1.2 and 6.8, respectively. Significant increase (P≤0.05 in the peak concentration (Cmax, the area under the curve (AUC0–∞, and the lymphatic targeting efficiency of Ptx was observed after the oral administration of the Ptx-loaded S-SEDDS to rats (20 mg/kg as Ptx. Our research suggests the prepared Ptx-loaded S-SEDDS can be a good candidate for the enhancement of BA and targeting drug delivery to the lymphatic system of Ptx.

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

    Directory of Open Access Journals (Sweden)

    Gregory M. Nelson

    2007-12-01

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

  4. Burden of lymphatic filariasis morbidity in an area of low endemicity in Brazil.

    Science.gov (United States)

    Netto, Maria José; Bonfim, Cristine; Brandão, Eduardo; Aguiar-Santos, Ana Maria; Medeiros, Zulma

    2016-11-01

    The Global Programme to Eliminate Lymphatic Filariasis has two main components: interrupting transmission of lymphatic filariasis (LF) and managing morbidity and preventing disability. However, interventions to prevent and manage LF-related disabilities in endemic communities have been of limited extent. The aim of this study was to describe the prevalence of morbidity and its correlation with filarial infection, thereby filling a gap that existed regarding the data on morbidity in Brazil. Presence of Wuchereria bancrofti microfilaria was investigated using the thick smear technique. Information on parasitosis-related clinical manifestations was obtained using a questionnaire applied by community health agents with previous training and capacitation to know about and identify the disease. To analyze correlations, Pearson's correlation coefficient was used with the corresponding statistical significance test. 23,673 individuals were investigated: 323 presented microfilaremia (1.36%) and 741 (3.13%) had clinical complaints that were attributable to LF. Acute dermatolymphangioadenitis (ADLA) was the most prevalent condition (2.2%). Lymphedema, ADLA and chyluria were more commonly reported among female patients. There were positive associations between all the clinical complaints reported and filarial infection. Hydrocele presented the most strongly positive association (r=0.699; pmanagement, through incorporating surveillance measures directed towards preventing disability and reducing the psychosocial and economic impact of the disease on poor populations living in areas endemic for LF. PMID:27427218

  5. [Lymphatic afferents and efferents of lymph nodes of the Barety's space. Anatomic review in adults].

    Science.gov (United States)

    Riquet, M; Debesse, B; Zouaoui, A; Hidden, G

    1990-06-01

    Lymph nodes of the Barety's space (LNLB) often involved in lung diseases are known under various names for a long time ago by pathologists. Our study involves 360 cadavers of adult subjects. The injection of a dye was performed by direct catheterization of a pulmonary segment. L.N.L.B. were directly or indirectly coloured (inter connected ganglionary network) more often from the lobes of the right lung, but from the lobes of the left lung too. From L.N.L.B. the lymphatic flow discharges in the venous confluent of the neck in the right side; in 1/4 of the cases a mediastinal efferent joints the left venous confluent too. From the lower lymph nodes of the space efferents can go to lymph nodes which are located right along the arch of the azygos vein (and then to the thoracic duct) and in the left side the group of left suprabronchial lymph nodes (then either to the thoracic duct in the mediastinum, or to the recurrent chain to the neck). At last, it seems that inside the lymph nodes themselves, lymphatic flows exist, the topography and the nature of which change according to the area interested by the injection. PMID:2289035

  6. [Thoracic duct collaterals of lymphatic and pulmonary origin. Anatomy and chylothorax after pulmonary surgery].

    Science.gov (United States)

    Riquet, M; Hidden, G; Debesse, B

    1989-01-01

    Dye injection of lung segments reveals the existence of lymphatic drainage of the lungs generally into cervical venous confluents and more rarely into the arch of the thoracic duct in the neck and also occasionally into the thoracic duct in the mediastinum. Direct drainage of the lymph into the thoracic duct was observed in 10 cases out of a series of 589 injections of lung segments in adult cadavers. In one half of cases, the thoracic duct was injected from the left suprabronchial lymph node chain, the origin of the left recurrent chain, and in one quarter of cases from the lateral anteroposterior right major azygos and left azygo-aortic lymph node chains, not recognised by the classical authors. More rarely, direct lymphatic collaterals drained certain segments of the lower lobes into the thoracic duct via the triangular ligament. Analysis of cases of chylothorax occurring after lung resection and observed in the authors' department or in the literature reveals that most of them can be attributed to a chyle leak from one of these pulmonary lymph collaterals. These pathways are probably also involved in the development of medical or idiopathic chylothorax. PMID:2686514

  7. Immunoprophylactic potential of filarial glutathione-s-transferase in lymphatic filariaisis

    Institute of Scientific and Technical Information of China (English)

    BalM; MandalN; AcharyKG; DasMK; KarSK

    2011-01-01

    Objective:To elucidates the immunoprophylactic potential of glutathion-s-transferase (GST) from cattle filarial parasite Setaria digitata (S. digitata) against lymphatic filariasis. Methods:GST was purified through affinity chromatography (SdGST) and chacterized by SDS-PAGE and Nano-LC MS/MS analysis. Antibody isotypes to SdGST were measured by ELISA. Antibody dependant cellular cytotoxicity (ADCC) was performed in vitro using sera from immunized animals and immune individuals. T-cell proliferation and cytokine response to SdGST in different groups of filariasis were measured. Immunoprophylactic potential of SdGST was evaluate in animal model. Results: SdGST exhibited 30-fold enhancement of enzyme activity over crude parasitic extract. It was found to be 26 kDa by SDS-PAGE. Nano LC-MS/MS analysis followed by blast search showed 100%homology with Dirofilaria immitis (D. immitis) and only 43%with Homo sapiens (H. sapiens). Immunoblotting analysis showed putatively immune individuals carry significant level of antibodies to SdGST as compared with microfilaraemics. Immunized sera and sera endemic normal could neutralize the enzymatic activity of SdGST and inducing in vitro cytotoxicity of microfilariae. Peripheral blood mononuclear cells (PBMC) from endemic normals upon stimulation with SdGST showed a mixed type of Th1/Th2 response. SdGST immunization clear microfilariae from circulation in S. digitata implanted mastomys. Conclusions:The heterologous GST could be potentially developed as a vaccine candidate against lymphatic filarial parasite.

  8. Shrinking the lymphatic filariasis map: update on diagnostic tools for mapping and transmission monitoring.

    Science.gov (United States)

    Rebollo, Maria P; Bockarie, Moses John

    2014-12-01

    Lymphatic filariasis (LF), which is highly endemic in 73 countries worldwide, is targeted for elimination by 2020. The strategy for achieving this goal is based on 4 sequential programmatic steps: mapping, Mass drug administration (MDA) implementation, post-MDA surveillance and verification of LF elimination. All 4 stages of the implementation process are dependent on the availability of user friendly and highly sensitive rapid diagnostic tools. By the end of 2012, 59 countries had completed mapping for LF and Eritrea was the only country yet to start the process. Rolling out new diagnostic tools to facilitate the mapping process will enable an accelerated shrinking of the LF map to zero endemic countries by 2020. When the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, diagnostic tools for LF were limited to clinical examination, detection of microfilaria (MF) by microscopy in night blood samples and detection of antibodies to native-antigen preparations. There has been a significant improvement in the traditional LF diagnostic methods in recent years and some new tools are now available. This paper provides an update on the human diagnostic tests available for LF and their current applications as tools in mapping and transmission monitoring. The values of entomological indicators and parasite detection and speciation methods applied to vector populations are also discussed. PMID:25225828

  9. Mapping of lymphatic filariasis: "to be (in English) or not to be".

    Science.gov (United States)

    Carme, B

    2010-12-01

    Despite lack of supporting evidence from epidemiologic studies and/or confirmed case reports over the last 30 years, maps in non-specialist works on tropical medicine as well as in documents from specialized organizations (e.g. WHO) systematically include Congo and Gabon, two French-speaking countries, within the zone of endemic filariasis due to Wuchereria bancrofti. One certainty is that no cases were found in field studies carried out in these countries in the late 1970s and 1980s but unfortunately published only in French. Studies that we carried out in the Congo between 1982 and 1987 as part of the National Project on Onchocerciasis and Other Filarioses confirmed the presence of four types of human filariasis: onchocerciasis, loaiasis filarioses caused by Mansonella perstans and M. streptocerca. However, there were no confirmed cases of lymphatic filariosis (bancroftosis). Hopefully the WHO program aimed at the elimination of lymphatic filariasis as a public health problem will provide up-to-date data on the distribution and endemicity of filariasis in Central Africa. Achievement of this objective will depend not only on carrying out new field studies but also on taking into account past studies published in languages other than Shakespeare's. PMID:21520639

  10. AN AMELIORATED DETECTION STATISTICS FOR ADAPTIVE MASK MEDIAN FILTRATION OF HEAVILY NOISED DIGITAL IMAGES

    Directory of Open Access Journals (Sweden)

    Geeta Hanji

    2016-11-01

    Full Text Available Noise reduction is an important area of research in image processing applications. The performance of the digital image noise filtering method primarily depends upon the accuracy of noise detection scheme. This paper presents an effective detector based, adaptive mask, median filtration of heavily noised digital images affected with fixed value (or salt and pepper impulse noise. The proposed filter presents a novel approach; an ameliorated Rank Ordered Absolute Deviation (ROAD statistics to judge whether the input pixel is noised or noise free. If a pixel is detected as corrupted, it is subjected to adaptive mask median filtration; otherwise, it is kept unchanged. Extensive experimental results and comparative performance evaluations demonstrate that the proposed filter outperforms the existing decision type, median based filters with powerful noise detectors in terms of objective performance measures and visual retrieviation accuracy.

  11. AMELIORATIVE EFFECTS OF TINOSPORA CORDIFOLIA IN SCIATICA PAIN INDUCED RATS

    OpenAIRE

    Thaakur Santhrani; Yaidikar Lavanya

    2012-01-01

    The present study was aimed at investigating the ameliorative effect of Tinospora cordifolia in sciatic nerve root Ligation -induced sciatica pain in rats. Adult male albino rats weighing 130-150gm were used for the study, and were divided into seven groups and ligation was performed on left sciatic nerve in group II to group VII. Tail cold-hyperalgesia, motor co-ordination tests, foot deformity, and total calcium levels were estimated to assess the extent of sciatica. Superoxide dismutase ...

  12. Response of Field Crops to Ameliorative Phosphorus Fertilization

    OpenAIRE

    KOVACEVIC, Vlado; Rastija, Mirta; KOMLJENOVIC, Ilija; BEGIC, Sabina; JOVIC, Jurica

    2014-01-01

    Different types of nutritional unbalances, including also low levels of plant available phosphorus (P), are often limiting factor of soil fertility in Croatia and in countries of the region, particularly in Bosnia and Herzegovina (B&H). Aim of this study was survey our recent investigations (eight stationary field experiments) of maize, soybean, wheat and barley responses to ameliorative P fertilization up to different levels (depending on the trial up to from 825 to 1580 kg P2O5 ha-1). Eithe...

  13. Biochar from commercially cultivated seaweed for soil amelioration

    Science.gov (United States)

    Roberts, David A.; Paul, Nicholas A.; Dworjanyn, Symon A.; Bird, Michael I.; de Nys, Rocky

    2015-04-01

    Seaweed cultivation is a high growth industry that is primarily targeted at human food and hydrocolloid markets. However, seaweed biomass also offers a feedstock for the production of nutrient-rich biochar for soil amelioration. We provide the first data of biochar yield and characteristics from intensively cultivated seaweeds (Saccharina, Undaria and Sargassum - brown seaweeds, and Gracilaria, Kappaphycus and Eucheuma - red seaweeds). While there is some variability in biochar properties as a function of the origin of seaweed, there are several defining and consistent characteristics of seaweed biochar, in particular a relatively low C content and surface area but high yield, essential trace elements (N, P and K) and exchangeable cations (particularly K). The pH of seaweed biochar ranges from neutral (7) to alkaline (11), allowing for broad-spectrum applications in diverse soil types. We find that seaweed biochar is a unique material for soil amelioration that is consistently different to biochar derived from ligno-cellulosic feedstock. Blending of seaweed and ligno-cellulosic biochar could provide a soil ameliorant that combines a high fixed C content with a mineral-rich substrate to enhance crop productivity.

  14. Arsenic toxicity in mice and its possible amelioration

    Institute of Scientific and Technical Information of China (English)

    R. J. Verma; Archana Vasu, Abdu; Alim Saiyed

    2004-01-01

    Oral administration of arsenic trioxide(3 and 6 mg/kg body weight/d) for 30 d caused, as compared with vehicle control, dose- dependent significant reductions in body weight, absolute weight, protein, glycogen, as well as, total, dehydro and reduced ascorbic acid contents both in the liver) and kidney of arsenic- treated mice. Succinic dehydrogenase(SDH) and phosphorylase(only in the liver activities were significantly reduced in a dose-dependent manner. Acid phosphatase activity was significantly decreased in the liver of low dose arsenic-treated animals; however, significant rise in its activity was observed in high dose group. As compared with vehicle control, treatment also caused significant dose-dependent reductions in SDH, alkaline phosphatase and acid phosphatase activities in the kidney of mice. Vitamin E cotreatment as well as, 30 d withdrawal of arsenic trioxide treatment with or without vitamin E caused significant amelioration in arsenic-induced toxicity in mice. Administration of vitamin E during withdrawal of treatment also caused significant amelioration as compared from only withdrawal of the treatment. It is concluded that vitamin E ameliorates arsenic-induced toxicities in the liver and kidney of mice.

  15. Study Regarding the Effectiveness of Manual Lymphatic Drainage in the Case of Patients with Breast Cancer that Present Lymphedema

    Directory of Open Access Journals (Sweden)

    Alexandru MIOC

    2013-06-01

    Full Text Available Lymphedema is defined as a persistent increase of tissue volume caused by the blocked or absent lymphatic drainage. The purpose of this study is to analyse the effectiveness of lymphatic drainage in the treatment of lymphedema after a mastectomy, with the aim of reducing the volume of the lymphedema and improving overall symptomatology, as well as providing information regarding the impact of this treatment on quality-of-life and the physical limitations of these patients. With these objectives in mind, a series of articles evaluating the effectiveness of manual lymphatic drainage in the case of patients with breast cancer and lymphedema have been studied. The parameters under observation were: duration of lymphedema reduction and improved symptomatology (pain, a feeling of swelling of the upper limb, functional limitation, and patient dissatisfaction towards their body image. Following this analysis, one can conclude that the association of manual lymphatic drainage to physical exercise and physiotherapy has produced changes in the volume of the limb affected by the lymphedema; however, its isolated use has not resulted in significant changes.

  16. Noninvasive real-time fluorescence imaging of the lymphatic uptake of BSA-IRDye 680 conjugate administered subcutaneously in mice.

    Science.gov (United States)

    Wu, Fang; Bhansali, Suraj G; Tamhane, Mitalee; Kumar, Rajiv; Vathy, Lisa A; Ding, Hong; Yong, Ken-Tye; Bergey, Earl J; Prasad, Paras N; Morris, Marilyn E

    2012-05-01

    The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time noninvasive fluorescence imaging. BSA labeled with near-infrared dye (IRDye) 680 was used as a model protein-dye conjugate. The conjugation of BSA with IRDye 680 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size-exclusion high-performance liquid chromatography and SDS-PAGE demonstrated that the IRDye 680-labeled BSA conjugate in the lymph node (LN) homogenate samples was stable at physiological temperature (37°C) for at least 5 days. Whole-body noninvasive optical imaging of hairless SKH-1 mice was performed after subcutaneous (s.c.) injection (dose = 0.1 mg/kg) into the front footpad. Noninvasive fluorescence imaging demonstrated that BSA-IRDye 680 conjugates were dynamically taken up by the lymphatic system, accumulated in the axillary LNs and then cleared, indicating that lymphatic transport plays a role in the absorption of BSA. Ex vivo tissue imaging of LN homogenates provided confirmatory data with respect to the uptake of fluorescent-labeled BSA determined by in vivo imaging. Noninvasive real-time imaging of LNs provides a novel tool for evaluating uptake and accumulation of fluorescent-labeled proteins by the lymphatic system after s.c. injection in a mouse model.

  17. Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation

    Energy Technology Data Exchange (ETDEWEB)

    Okazaki, Hideki; Tokumaru, Sho; Hanakawa, Yasushi; Shiraishi, Ken; Shirakata, Yuji; Dai, Xiuju; Yang, Lijun; Tohyama, Mikiko; Hashimoto, Koji [Department of Dermatology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295 (Japan); Sayama, Koji, E-mail: sayama@m.ehime-u.ac.jp [Department of Dermatology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295 (Japan)

    2011-09-02

    Highlights: {yields} VEGF-A enhanced lymphatic endothelial cell migration and increased tube formation. {yields} VEGF-A treated lymphatic endothelial cell showed activation of STAT3. {yields} Dominant-negative STAT3 inhibited VEGF-A-induced lymphatic endothelial cell migration and tube formation. -- Abstract: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific growth factor that regulates endothelial functions, and signal transducers and activators of transcription (STATs) are known to be important during VEGF receptor signaling. The aim of this study was to determine whether STAT3 regulates VEGF-induced lymphatic endothelial cell (LEC) migration and tube formation. VEGF-A (33 ng/ml) enhanced LEC migration by 2-fold and increased tube length by 25% compared with the control, as analyzed using a Boyden chamber and Matrigel assay, respectively. Western blot analysis and immunostaining revealed that VEGF-A induced the nuclear translocation of phosphorylated STAT3 in LECs, and this translocation was blocked by the transfection of LECs with an adenovirus vector expressing a dominant-negative mutant of STAT3 (Ax-STAT3F). Transfection with Ax-STAT3F also almost completely inhibited VEGF-A-induced LEC migration and tube formation. These results indicate that STAT3 is essential for VEGF-A-induced LEC migration and tube formation and that STAT3 regulates LEC functions.

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

    Science.gov (United States)

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

    2014-01-01

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

  19. MID TERM ASSESSMENT OF MASS DRUG ADMINISTRATION IN LYMPHATIC FILARIASIS ENDEMIC AREA OF DAMOH AND SAGAR DISTRICT OF MADHYA PRADESH

    OpenAIRE

    Mohan; Yash; Ankur

    2015-01-01

    BACKGROUND: Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is an important public health problem in India. Filariasis is a major social and the fourth most common cause of disability all over the globe. Filariasis is endemic in 17 States and six Union Territories, with about 553 million people at risk of infection...

  20. Influence of the type of surfactant and the degree of dispersion on the lymphatic transport of halofantrine in conscious rats

    DEFF Research Database (Denmark)

    Karpf, Ditte M; Holm, René; Kristensen, Henning G;

    2004-01-01

    absorption of Hf was similar for the three vehicles. CONCLUSIONS: The emulsified vehicles favor an increased lymphatic transport of Hf. The portal transport of Hf was not significantly different for the three vehicles. This indicates that a different degree of dispersion of the TG vehicle can change...